Der Haarfollikel ist zugleich Quelle und Wirkort verschiedener Zytokine und Neurotrophine. Zytokine können die Expression von Neurotrophinen und ihrer Rezeptoren in verschiedenen extrakutanen Geweben modifizieren. Daher wurde untersucht, ob Zytokine diese Wirkung auch am Haarfollikel entfalten können. Mittels Immunfluoreszenz wurden Kryostatschnitte von Rückenhaut der C57BL/6-Maus dahingehend untersucht, ob die intradermale Injektion von proinflammatorischen Zytokinen (IL-1 beta, TNF-alpha, IFN-gamma), topische Gabe von Dexamethason oder die intraperitoneale Behandlung mit Cyclosporin A (CsA) die intra- und extrafollikuläre Immunreaktivität von NGF, BDNF, NT-4, NT-3 oder ihrer hochaffinen Rezeptoren Trk-A (NGF), Trk-B (BDNF, NT-4), Trk-C (NT-3) oder des niedrigaffinen Rezeptors p75NTR verändert. Alle Haarfollikel befanden sich im Wachstumsstadium des Haarzyklus (Anagen VI). Alle drei untersuchten Zytokine sowie ein Cocktail von IL-1 beta, TNF-alpha und IFN-gamma regulierten die NGF-Immunreaktivität (IR) in der proximalen äußeren Wurzelscheide (ÄWS) und in der Haarmatrix (HM) von Anagen-VI-Haarfollikeln hoch. Der Zytokincocktail regulierte ebenfalls sehr deutlich die NT-3- und NT-4-IR in der murinen Epidermis hoch. Zusätzlich erhöhte dieser Cocktail die NT-4-IR in spezifischen Zellpopulationen von HM und proximaler ÄWS sowie die p75 NTR-Expression in der dermalen Papille. Interessanterweise erhöhte die Behandlung mit CsA in gleicher Weise wie die einzelnen Zytokine und der Zytokincocktail die NGF-IR in HM und proximaler ÄWS. Dexamethason bewirkte in dieser Arbeit keine Veränderungen der Expression von Neurotrophinen bzw. ihrer Rezeptoren. Somit konnte gezeigt werden, daß sowohl bestimmte proinflammatorische Zytokine als auch CsA die intra- und extrafollikuläre Expression von Neurotrophinen und ihrer Rezeptoren verändern. / The hair follicle is both, source and target of various cytokines and neurotrophins (NTs), and various cytokines are recognized to alter expression of NTs and their receptors. Therefore I examined, whether cytokines can alter the expression of NTs also in the hair follicle. By means of immunofluorescence, it was investigated on cryostat sections of murine back skin (C57BL/6- mice), whether and how the intradermal injection of proinflammatory cytokines (IL-1 beta, TNF-apha, IFN-gamma, topical dexamethasone or cyclosporin A (CsA) treatment i.g. alter the intra- and extrafollicular immunoreactivity (IR) of NGF, BDNF, NT-4, NT-3 or that of the corresponding high affinity receptors Trk-A (NGF), Trk-B (BDNF, NT-4), Trk-C (NT-3) or their common low affinity receptor p75NTR. All hair follicles were in the growth stage of the hair cycle (Anagen VI). All these cytokines as well as a cocktail of IFN-gamma, IL-1 beta and TNF-alpha increased the NGF-IR in the proximal outer root sheath (ORS) and in the hair matrix (HM) of Anagen VI hair follicles. The cytokine cocktail upregulated NT-3 and NT-4-IR in murine epidermis, increased NT-4-IR in selected cell populations of the HM and the proximal ORS. It enhanced also the p75NTR expression in the dermal papilla. Surprisingly, intraperitoneal treatment with CsA also increased the NGF-IR in HM and ORS, while dexamethasone showed no effect. This demonstrates that selected proinflammatory cytokines and CsA alter the cutaneous intra- and extrafollicular expression of NTs and their receptors.

Made available in DSpace on 2016-03-22T17:27:35Z (GMT). No. of bitstreams: 1 SharonMFerreir.pdf: 2163870 bytes, checksum: d5e466194ea4c397ec8640eb900fa160 (MD5) Previous issue date: 2014-10-27 / % Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders that affect approximately 17% of the population in a lifetime. Neurotrophins (NGF) are a group of structurally related proteins, which control the development and differentiation of nerve cells that play a role in cellular migration proliferation, differentiation and phenotypic maintenance central nervous system development. Thus, the role of NGF in neuronal plasticity and support, may suggests that these NGF plays an important action in the etiology and pathophysiology of suicide individuals. Therefore, the aim of this study was to evaluate serum levels of NGF in healthy and depressed person with and without suicide risk in a population-based sample of individuals. This study was performed 47 individuals with current depressive episode and suicide risk without a history of mania, and allocated to major depression and suicide risk groups. Two groups of 47 individuals each, were matched by sex and age: the active control group was composed of those with current depressive episode without risk of suicide; while the population control group included individuals with no history of affective disorder.This study was conducted by a questionnaire with demographic questions (gender, ethnicity, age and education level). After the diagnostic interview, a collection of blood from each individual was performed. Measurement of serum levels of NGF by ELISA. The comparison between the levels of NGF with the group of depressed individuals at risk for suicide without a depressed suicide risk and healthy control was performed by ANOVA with Bonferroni through post-hoc test.. NGF levels were significantly lower (p <0.001) in the groups with major depression and major depression with suicide risk (92.39 ± 41.21ng / mL and 100.99 ± 35.08ng / mL, 40 respectively) compared to the control group (149.81 ± 65.94 ng / ml). In conclusion, our study demonstrates that reducing the levels of NGF can be used as a marker TDM, compared with healthy individuals / O transtorno depressivo maior (TDM) é um dos distúrbios psiquiátricos de maior prevalência que acomete em aproximadamente 17% da população geral ao longo da vida. As neurotrofinas, dentre elas o fator de crescimento neural (NGF), são um grupo de proteínas relacionadas estruturalmente, as quais controlam o desenvolvimento e a diferenciação das células nervosas que desempenham um papel importante na proliferação celular, migração, diferenciação fenotípica e manutenção do sistema nervoso central em desenvolvimento. Devido ao importante papel das NGF na plasticidade e suporte neuronal, sugere-se que o NGF desempenha um importante papel na etiologia e fisiopatologia do suicídio. Portanto o objetivo deste estudo foi avaliar os níveis séricos de NGF em indivíduos saudáveis e deprimidos com e sem risco de suicídio de uma amostra de base populacional. O estudo envolveu 47 indivíduos para compor o grupo com depressão maior e risco de suicídio. Outros dois grupos, de 47 indivíduos cada, foram pareados por sexo e idade: o grupo controle ativo foi composto por aqueles que apresentaram episódio depressivo atual, sem risco de suicídio; enquanto o grupo controle populacional contemplou os indivíduos sem história de transtorno afetivo. O estudo foi realizado por um questionário com questões sociodemográficas (sexo, etnia, idade e escolaridade). Os níveis séricos de NGF foram analisados através da técnica de ELISA. A comparação entre os níveis de NGF com o grupo de indivíduos deprimidos com risco de suicídio, deprimidos sem risco de suicídio e controle populacional foi realizada por ANOVA, com post-hoc através do teste Bonferroni. Os níveis de NGF foram significativamente menores (p<0.001) nos grupos com depressão maior e depressão maior com risco de suicídio 38 (92.39±41.21ng/mL e 100.99±35.08ng/mL, respectivamente) quando comparados ao grupo controle (149.81±65.94ng/mL).Concluimos que a redução dos níveis de NGF podem ser utilizados como um marcador de estado em TDM, em comparação com os de indivíduos saudáveis

A lesão do nervo alveolar inferior (NAI) está relacionada à prática odontológica. Estudos demonstram que a laserterapia promove a regeneração do nervo e analgesia. Usando o modelo de esmagamento do NAI associado à laserterapia avaliamos a reparação nervosa e a nocicepção dos animais antes da lesão, e após o tratamento. Vimos que o laser reverteu o comportamento hipernociceptivo e que a modulação de receptores para glutamato, de neurotrofinas, do receptor de potencial transiente vanilóide do subtipo 1, da substância p e do peptídeo relacionado ao gene da calcitonina atuam neste processo. Adicionalmente, o laser alterou o microambiente da lesão modulando proteínas, como laminina, proteína mielínica zero e neurofilamentos, promovendo a regeneração do nervo; por microscopia eletrônica mostramos esta regeneração, evidenciada pelo aumento no número de fibras nervosas e da espessura da bainha de mielina no nervo do grupo tratado em relação ao grupo operado. Em conjunto, os resultados obtidos contribuem para reforçar o uso terapêutico do laser. / The inferior alveolar nerve injury (IAN) is related to dental practice. Studies have shown that LLLT promotes nerve regeneration and analgesia. Using IAN crush model associated with laser therapy we evaluated nerve repair and nociception of animals before injury and after treatment. We have seen that the laser reversed hipernociceptive behavior and modulation of glutamate receptors, neurotrophins, the transient potential vanilloid receptor subtype 1, substance P and calcitonin gene-related peptide act in this process. Additionally, the laser alter the microenvironment of the lesion modulating proteins such as laminin, myelin protein zero and neurofilaments, promoting nerve regeneration; electron microscopy showed this regeneration, evidenced by the increase in the number of nerve fibers and the thickness of the myelin sheath in nerve treated group compared to the surgery group. Together, these results contribute to enhance the therapeutic use of the laser.

Neuropeptides, such as substance P (SP) and bombesin/gastrin-releasing peptide (BN/GRP), and neurotrophins are involved in neuro-immunomodulatory processes and have marked trophic, growth-promoting and inflammation-modulating properties. The impact of these modulators in rheumatoid arthritis (RA) is, however, unclear. An involvement of the innervation, including the peptidergic innervation, is frequently proposed as an important factor for arthritic disease. Many patients with RA, but not all, benefit from treatment with anti-TNF medications. The studies presented here aimed to investigate the roles of neuropeptides, with an emphasis on BN/GRP and SP, and neurotrophins, especially with attention to brain-derived neurotrophic factor (BDNF), in human and murine knee joint tissue. The expression patterns of these substances and their receptors in synovial tissue from patients with either RA or osteoarthritis (OA) were studied in parallel with the levels of these factors in blood and synovial fluid from patients with RA and from healthy controls. Correlation studies were also performed comparing the levels of neuropeptides with those of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)]. Furthermore, the impact of anti-TNF treatment on the levels of BDNF in blood was investigated. In a murine model of RA, the expression of these substances on articular chondrocytes along with their expression in synovial tissue was investigated. The expression of BN/GRP in human synovial tissue was confined to fibroblast-like and mononuclear-like cells whereas SP was detected in nerve-related structures. Receptors for these neuropeptides (GRP-R and NK-1R) were frequently present in blood vessel walls, and on fibroblast-like and mononuclear-like cells. The expression of BDNF and its receptors, p75 neurotrophin receptor and TrkB, was mainly confined to nerve structures. The levels of SP, and particularly those of BN/GRP, in synovial fluid and peripheral blood correlated with the levels of pro-inflammatory cytokines. There were clearly more correlations between SP-BN/GRP and inflammatory parameters than between BDNF and these factors. Plasma levels of BDNF were decreased following anti-TNF-treatment. In the joints of the murine model, there was a marked expression of neurotrophins, neurotrophin receptors and NK-1R/GRP-R in the articular chondrocytes. The expression was down-regulated in the arthritic animals. A neurotrophin system was found to develop in the inflammatory infiltrates of the synovium in the arthritic mice. The results presented suggest that there is a local, and not nerve-related, supply of BN/GRP in the human synovial tissue. Furthermore, BN/GRP and SP have marked effects in the synovial tissue of patients with RA, i.e., there were abundant receptor expressions, and these neuropeptides are, together with cytokines, likely to be involved in the neuro-immunomodulation that occurs in arthritis. The observations do on the whole suggest that the neuropeptides, rather than BDNF, are related to inflammatory processes in the human knee joint. A new effect of anti-TNF treatment; i.e., lowering plasma levels of BDNF, was observed. Severe arthritis, as in the murine model, lead to a decrease in the levels of neurotrophin, and neurotrophin and neuropeptide receptor expressions in the articular cartilage. This fact might be a drawback for the function of the chondrocytes. Certain differences between the expression patterns in the synovial tissue of the murine model and those of human arthritic synovial tissue were noted. It is obvious that local productions in the synovial tissue, nerve-related supply in this tissue and productions in chondrocytes to different extents occur for the investigated substances.

Introdução: Há um reconhecimento crescente de que a fisiopatologia da esquizofrenia (SZ) pode ser o resultado de uma desregulação na plasticidade sináptica, com alterações nas neurotrofinas. O fator neurotrófico derivado do cérebro (BDNF) é a neurotrofina mais amplamente distribuída no sistema nervoso central e é considerada uma proteína crucial na doença psiquiátrica. Evidência recente aponta o papel da dieta na regulação do BDNF. De acordo com os registros, em modelos animais, intervenções ambientais, tais como o tipo de dieta e interações sociais e familiares, alteram a concentração de BDNF. Objetivo: Nós realizamos um estudo transversal para examinar o efeito da intervenção da dieta nos níveis séricos de BDNF na esquizofrenia. Método: A amostra do estudo constou de 67 pacientes ambulatoriais caucasianos (51 homens e 16 mulheres) que participam do Programa de Esquizofrenia do Hospital de Clínicas de Porto Alegre (HCPA). Os pacientes foram divididos em 2 grupos: com dieta hipocalórica e sem dieta hipocalórica. Dados de peso, altura e índice de massa corporal (IMC) foram coletados por um nutricionista ou um psiquiatra. A dieta hipocalórica consistiu na redução da ingestão de gordura saturada e açúcar, e no aumento da ingestão de frutas e vegetais. Foram coletadas amostras de 5ml de sangue de cada sujeito, através de venipunção sem anticoagulantes e os níveis séricos de BDNF foram medidos pelo método de "sandwich ELISA", utilizando um kit comercial de acordo com as instruções do fabricante.A amostra sangüínea foi obtida em um período de um mês, no mínimo, após a exposição à intervenção dietética. Resultados: Os níveis séricos de BDNF foram significativamente mais altos em pacientes com esquizofrenia submetidos à dieta hipocalórica (p = 0,023). Discussão: Junto às evidências prévias do efeito da dieta e da nutrição sobre os sistemas endócrino e imunológico e, conseqüentemente, sobre a expressão gênica, bioquímica e processos do envelhecimento, o estudo evidenciou que a dieta influenciou o curso e as respostas clínicas da doença psiquiátrica. Pesquisas adicionais para examinar a interação entre padrões de comportamento alimentar e a fisiopatologia subjacente podem resultar em insights sobre quais decisões baseadas em evidências, considerando intervenções dietéticas, podem ser tomadas em pessoas com doenças psiquiátricas importantes, tal como a esquizofrenia. / Introduction: There is an increasing recognition that the pathophysiology of schizophrenia (SZ) may be the result of a deregulation in synaptic plasticity, with downstream alterations in neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system and is regarded as a critically important protein in psychiatric illness. Recent evidence points to role for diet in regulating BDNF. In animal models, environmental interventions, in the form of diet, housing and social interactions, have been reported to alter the concentration of BDNF. Objective: We assessed a cross-sectional study, in order to examine the effect of diet intervention on BDNF serum levels in schizophrenia. Method: The study sample comprised 67 Caucasian outpatients (51 males and 16 females), currently participating in the Schizophrenia Program of a major teaching and public hospital in Porto Alegre, Brazil (Hospital de Clínicas de Porto Alegre - HCPA). Patients were divided into 2 groups: the ones on a hypocaloric diet and the ones not on a hypocaloric diet. Weight, height and BMI data were collected by a nutritionist or a psychiatrist. The hypocaloric diet consisted on reduction of saturated fat intake and sugar and increase in fruit and vegetables intake. Each subject had 5ml blood samples collected by venipuncture without anticoagulants and the BDNF serum levels were measured with a sandwich-ELISA, using a commercial kit according to the manufacturer's instructions. The blood sample was obtained a minimum of one month after the exposure of the dietary intervention. Results: Serum BDNF levels were significantly higher in patients with schizophrenia on hypocaloric diet (p=0.023). Conclusions: In addition to previous evidences of the effect of diet and nutrition over immune and endocrine systems and thus over gene expression, biochemistry and aging processes, the study evidenced that diet influenced the course and clinical outcomes of psychiatric illness. Additional research examining the interaction among patterns of nutritional food behavior with underling physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as schizophrenia.

Introdução: Há um reconhecimento crescente de que a fisiopatologia da esquizofrenia (SZ) pode ser o resultado de uma desregulação na plasticidade sináptica, com alterações nas neurotrofinas. O fator neurotrófico derivado do cérebro (BDNF) é a neurotrofina mais amplamente distribuída no sistema nervoso central e é considerada uma proteína crucial na doença psiquiátrica. Evidência recente aponta o papel da dieta na regulação do BDNF. De acordo com os registros, em modelos animais, intervenções ambientais, tais como o tipo de dieta e interações sociais e familiares, alteram a concentração de BDNF. Objetivo: Nós realizamos um estudo transversal para examinar o efeito da intervenção da dieta nos níveis séricos de BDNF na esquizofrenia. Método: A amostra do estudo constou de 67 pacientes ambulatoriais caucasianos (51 homens e 16 mulheres) que participam do Programa de Esquizofrenia do Hospital de Clínicas de Porto Alegre (HCPA). Os pacientes foram divididos em 2 grupos: com dieta hipocalórica e sem dieta hipocalórica. Dados de peso, altura e índice de massa corporal (IMC) foram coletados por um nutricionista ou um psiquiatra. A dieta hipocalórica consistiu na redução da ingestão de gordura saturada e açúcar, e no aumento da ingestão de frutas e vegetais. Foram coletadas amostras de 5ml de sangue de cada sujeito, através de venipunção sem anticoagulantes e os níveis séricos de BDNF foram medidos pelo método de "sandwich ELISA", utilizando um kit comercial de acordo com as instruções do fabricante.A amostra sangüínea foi obtida em um período de um mês, no mínimo, após a exposição à intervenção dietética. Resultados: Os níveis séricos de BDNF foram significativamente mais altos em pacientes com esquizofrenia submetidos à dieta hipocalórica (p = 0,023). Discussão: Junto às evidências prévias do efeito da dieta e da nutrição sobre os sistemas endócrino e imunológico e, conseqüentemente, sobre a expressão gênica, bioquímica e processos do envelhecimento, o estudo evidenciou que a dieta influenciou o curso e as respostas clínicas da doença psiquiátrica. Pesquisas adicionais para examinar a interação entre padrões de comportamento alimentar e a fisiopatologia subjacente podem resultar em insights sobre quais decisões baseadas em evidências, considerando intervenções dietéticas, podem ser tomadas em pessoas com doenças psiquiátricas importantes, tal como a esquizofrenia. / Introduction: There is an increasing recognition that the pathophysiology of schizophrenia (SZ) may be the result of a deregulation in synaptic plasticity, with downstream alterations in neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system and is regarded as a critically important protein in psychiatric illness. Recent evidence points to role for diet in regulating BDNF. In animal models, environmental interventions, in the form of diet, housing and social interactions, have been reported to alter the concentration of BDNF. Objective: We assessed a cross-sectional study, in order to examine the effect of diet intervention on BDNF serum levels in schizophrenia. Method: The study sample comprised 67 Caucasian outpatients (51 males and 16 females), currently participating in the Schizophrenia Program of a major teaching and public hospital in Porto Alegre, Brazil (Hospital de Clínicas de Porto Alegre - HCPA). Patients were divided into 2 groups: the ones on a hypocaloric diet and the ones not on a hypocaloric diet. Weight, height and BMI data were collected by a nutritionist or a psychiatrist. The hypocaloric diet consisted on reduction of saturated fat intake and sugar and increase in fruit and vegetables intake. Each subject had 5ml blood samples collected by venipuncture without anticoagulants and the BDNF serum levels were measured with a sandwich-ELISA, using a commercial kit according to the manufacturer's instructions. The blood sample was obtained a minimum of one month after the exposure of the dietary intervention. Results: Serum BDNF levels were significantly higher in patients with schizophrenia on hypocaloric diet (p=0.023). Conclusions: In addition to previous evidences of the effect of diet and nutrition over immune and endocrine systems and thus over gene expression, biochemistry and aging processes, the study evidenced that diet influenced the course and clinical outcomes of psychiatric illness. Additional research examining the interaction among patterns of nutritional food behavior with underling physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as schizophrenia.

Introdução: Há um reconhecimento crescente de que a fisiopatologia da esquizofrenia (SZ) pode ser o resultado de uma desregulação na plasticidade sináptica, com alterações nas neurotrofinas. O fator neurotrófico derivado do cérebro (BDNF) é a neurotrofina mais amplamente distribuída no sistema nervoso central e é considerada uma proteína crucial na doença psiquiátrica. Evidência recente aponta o papel da dieta na regulação do BDNF. De acordo com os registros, em modelos animais, intervenções ambientais, tais como o tipo de dieta e interações sociais e familiares, alteram a concentração de BDNF. Objetivo: Nós realizamos um estudo transversal para examinar o efeito da intervenção da dieta nos níveis séricos de BDNF na esquizofrenia. Método: A amostra do estudo constou de 67 pacientes ambulatoriais caucasianos (51 homens e 16 mulheres) que participam do Programa de Esquizofrenia do Hospital de Clínicas de Porto Alegre (HCPA). Os pacientes foram divididos em 2 grupos: com dieta hipocalórica e sem dieta hipocalórica. Dados de peso, altura e índice de massa corporal (IMC) foram coletados por um nutricionista ou um psiquiatra. A dieta hipocalórica consistiu na redução da ingestão de gordura saturada e açúcar, e no aumento da ingestão de frutas e vegetais. Foram coletadas amostras de 5ml de sangue de cada sujeito, através de venipunção sem anticoagulantes e os níveis séricos de BDNF foram medidos pelo método de "sandwich ELISA", utilizando um kit comercial de acordo com as instruções do fabricante.A amostra sangüínea foi obtida em um período de um mês, no mínimo, após a exposição à intervenção dietética. Resultados: Os níveis séricos de BDNF foram significativamente mais altos em pacientes com esquizofrenia submetidos à dieta hipocalórica (p = 0,023). Discussão: Junto às evidências prévias do efeito da dieta e da nutrição sobre os sistemas endócrino e imunológico e, conseqüentemente, sobre a expressão gênica, bioquímica e processos do envelhecimento, o estudo evidenciou que a dieta influenciou o curso e as respostas clínicas da doença psiquiátrica. Pesquisas adicionais para examinar a interação entre padrões de comportamento alimentar e a fisiopatologia subjacente podem resultar em insights sobre quais decisões baseadas em evidências, considerando intervenções dietéticas, podem ser tomadas em pessoas com doenças psiquiátricas importantes, tal como a esquizofrenia. / Introduction: There is an increasing recognition that the pathophysiology of schizophrenia (SZ) may be the result of a deregulation in synaptic plasticity, with downstream alterations in neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system and is regarded as a critically important protein in psychiatric illness. Recent evidence points to role for diet in regulating BDNF. In animal models, environmental interventions, in the form of diet, housing and social interactions, have been reported to alter the concentration of BDNF. Objective: We assessed a cross-sectional study, in order to examine the effect of diet intervention on BDNF serum levels in schizophrenia. Method: The study sample comprised 67 Caucasian outpatients (51 males and 16 females), currently participating in the Schizophrenia Program of a major teaching and public hospital in Porto Alegre, Brazil (Hospital de Clínicas de Porto Alegre - HCPA). Patients were divided into 2 groups: the ones on a hypocaloric diet and the ones not on a hypocaloric diet. Weight, height and BMI data were collected by a nutritionist or a psychiatrist. The hypocaloric diet consisted on reduction of saturated fat intake and sugar and increase in fruit and vegetables intake. Each subject had 5ml blood samples collected by venipuncture without anticoagulants and the BDNF serum levels were measured with a sandwich-ELISA, using a commercial kit according to the manufacturer's instructions. The blood sample was obtained a minimum of one month after the exposure of the dietary intervention. Results: Serum BDNF levels were significantly higher in patients with schizophrenia on hypocaloric diet (p=0.023). Conclusions: In addition to previous evidences of the effect of diet and nutrition over immune and endocrine systems and thus over gene expression, biochemistry and aging processes, the study evidenced that diet influenced the course and clinical outcomes of psychiatric illness. Additional research examining the interaction among patterns of nutritional food behavior with underling physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as schizophrenia.

A lesão do nervo alveolar inferior (NAI) está relacionada à prática odontológica. Estudos demonstram que a laserterapia promove a regeneração do nervo e analgesia. Usando o modelo de esmagamento do NAI associado à laserterapia avaliamos a reparação nervosa e a nocicepção dos animais antes da lesão, e após o tratamento. Vimos que o laser reverteu o comportamento hipernociceptivo e que a modulação de receptores para glutamato, de neurotrofinas, do receptor de potencial transiente vanilóide do subtipo 1, da substância p e do peptídeo relacionado ao gene da calcitonina atuam neste processo. Adicionalmente, o laser alterou o microambiente da lesão modulando proteínas, como laminina, proteína mielínica zero e neurofilamentos, promovendo a regeneração do nervo; por microscopia eletrônica mostramos esta regeneração, evidenciada pelo aumento no número de fibras nervosas e da espessura da bainha de mielina no nervo do grupo tratado em relação ao grupo operado. Em conjunto, os resultados obtidos contribuem para reforçar o uso terapêutico do laser. / The inferior alveolar nerve injury (IAN) is related to dental practice. Studies have shown that LLLT promotes nerve regeneration and analgesia. Using IAN crush model associated with laser therapy we evaluated nerve repair and nociception of animals before injury and after treatment. We have seen that the laser reversed hipernociceptive behavior and modulation of glutamate receptors, neurotrophins, the transient potential vanilloid receptor subtype 1, substance P and calcitonin gene-related peptide act in this process. Additionally, the laser alter the microenvironment of the lesion modulating proteins such as laminin, myelin protein zero and neurofilaments, promoting nerve regeneration; electron microscopy showed this regeneration, evidenced by the increase in the number of nerve fibers and the thickness of the myelin sheath in nerve treated group compared to the surgery group. Together, these results contribute to enhance the therapeutic use of the laser.

In assessing and assimilating the neurodevelopmental basis of the so-called movement disorders it is probably useful to establish certain concepts that will modulate both the variation and selection of affliction, mechanisms-processes and diversity of disease states. Both genetic, developmental and degenerative aberrations are to be encompassed within such an approach, as well as all deviations from the necessary components of behaviour that are generally understood to incorporate "normal" functioning. In the present treatise, both conditions of hyperactivity/hypoactivity, akinesia and bradykinesia together with a constellation of other symptoms and syndromes are considered in conjunction with the neuropharmacological and brain morphological alterations that may or may not accompany them, e.g. following neonatal denervation. As a case in point, the neuroanatomical and neurochemical points of interaction in Attention Deficit and Hyperactivity disorder (ADHD) are examined with reference to both the perinatal metallic and organic environment and genetic backgrounds. The role of apoptosis, as opposed to necrosis, in cell death during grain development necessitates careful considerations of the current explosion of evidence for brain nerve growth factors, neurotrophins and cytokines, and the processes regulating their appearance, release and fate. Some of these processes may posses putative inherited characteristics, like asynuclein, others may to greater or lesser extents be endogenous or semi-endogenous (in food), like the tetrahydroisoquinolines, others exogenous until inhaled or injested through environmental accident, like heavy metals, e.g. mercury. Another central concept of neurodevelopment is cellular plasticity, thereby underlining the essential involvement of glutamate systems and N-methyl-D-aspartate receptor configurations. Finally, an essential assimilation of brain development in disease must delineate the relative merits of inherited as opposed to environmental risks not only for the commonly-regarded movement disorders, like Parkinson's disease, Huntington's disease and epilepsy, but also for afflictions bearing strong elements of psychosocial tragedy, like ADHD, autism and Savantism.

O consumo de dieta ocidental altamente palatável e hipercalórica expõe os indivíduos, desde a primeira infância, a uma alimentação obesogênica. Essa dieta aumenta o prazer relacionado ao consumo alimentar estimulando o sistema de recompensa e alterando vias de sinalização do sistema nervoso central (SNC). Esses eventos são relacionados à perda do controle adequado do apetite. Por outro lado, exposição ao estresse também tem importante relação com controle alimentar. Uma importante fonte de estresse é a deprivação materna (DM) no período neonatal, trazendo prejuízos ao indivíduo ao longo da vida. Estudos em animais têm demonstrado que o estresse induzido pela DM nesse período provoca alterações neuroquímicas. Essas alterações têm sido relacionadas a transtornos mentais como ansiedade e depressão, assim como, obesidade na idade adulta. Considerando a relevância do tema, nessa dissertação avaliamos o efeito da DM no período neonatal e/ou exposição à dieta hipercalórica (leite condensado) após o desmame sobre parâmetros de desenvolvimento neuromotor, ponderais, comportamentais e neuroquímicos em ratos Wistar adultos jovens machos e fêmeas. Foram utilizados 64 ratos Wistar machos e fêmeas distribuídos em quatro grupos: Controle (C) – sem DM e exposto à dieta padrão; Deprivação Materna (DM)- animais submetidos à DM (P1-P10) e exposto à dieta padrão; Dieta Hipercalórica (DH) - sem DM e exposto à dieta hipercalórica (alimento palatável/leite condensado); e Deprivação Materna e Dieta Hipercalórica (DMDH)- animais submetidos à DM (P1-P10) e expostos à dieta hipercalórica (alimento palatável/leite condensado). Os efeitos da DM nos padrões de reflexos iniciais nos filhotes foram avaliados por meio dos testes de geotaxia negativa e endireitamento postural, assim como seus efeitos sobre a resposta nociceptiva avaliada por meio do teste da Placa Quente (PQ) e do Tail-Flick (TFL). Avaliamos também o comportamento do tipo ansioso por meio do teste do Labirinto em Cruz Elevado - Elevated Plus Maze (EPM) e a atividade locomotora pelo teste de Campo Aberto (CA) antes do desmame (P21). A partir de P21, os animais dos grupos DH e DMDH foram expostos a uma dieta hipercalórica/alimento palatável (leite condensado) por três semanas e novamente avaliados a resposta nociceptiva, o comportamento do tipo ansioso e a atividade locomotora. Salientamos que foi analisado o efeito do gênero sobre todos os parâmetros analisados. Após a segunda leva de testes comportamentais, os animais foram mortos (P44) e retirados córtex cerebral, hipocampo e hipotálamo para a realização de dosagens bioquímicas. Foram dosados níveis do fator de desenvolvimento neuronal do encéfalo (BDNF), fator de crescimento neuronal 1 (NGF-1) e de citocinas pro-inflamatórias (IL6 e TNF-α) e anti-inflamatória (IL10). Nossos resultados demonstram que a exposição à DM induz, em curto prazo (entre P20 e P21), alterações no desenvolvimento motor inicial, resposta nociceptiva térmica (aumento do limiar nociceptivo –PQ e TFL-fêmeas), aumento da atividade locomotora de fêmeas devido ao maior número de cruzamentos externos e do tempo de grooming em machos, o que pode estar relacionado a alterações em sistema dopaminérgico (teste CA); aumento no tempo de permanência nos braços abertos dos animais deprivados sugerindo um efeito ansiolítico dessa intervenção, aumento no número de non-protected head dipping (NPHD) em machos, comportamentos relacionados à atividade exploratória e avaliação de risco (teste do EPM). Os efeitos tardios da DM, avaliados entre P42 e P43, foram observados na resposta nociceptiva (diminuição do limiar nociceptivo dos machos -TFL) e no teste EPM apenas os machos apresentaram maior número de rearings, indicativo de aumento na atividade exploratória dependente de gênero da DM. Quando expostos à DH, os machos apresentaram maior ganho de peso e índice de Lee. A DH induziu um aumento no peso relativo de tecido adiposo, independente do sexo. Foram observados efeitos tardios da DM e do gênero sobre os níveis de BDNF nas estruturas cerebrais avaliadas. Efeito da exposição à DH foi observado apenas nos níveis hipotalâmicos de NGF-1. Fêmeas apresentaram níveis mais elevados de BDNF e IL-6 em hipocampo e hipotálamo, e de TNF-α em hipotálamo. Em níveis corticais de IL10 houve interação entre gênero e DM. Concluindo, esses achados contribuem para um maior entendimento dos possíveis efeitos da exposição precoce a um estressor e/ou ao alimento palatável na infância/adolescência, demonstrando diferentes respostas de acordo com gênero às intervenções propostas. Além disso, diferenças entre o gênero per se foram observadas, sugerindo a importância de incluir ambos os sexos nas investigações pré-clínicas a fim de trazer maior translacionalidade aos estudos. / The consumption of a highly palatable and hypercaloric Western diet exposes individuals, from early infancy, to an obesogenic diet. This diet increases the pleasure related to food consumption by stimulating the reward system and altering Central Nervous System (CNS) signaling pathways. These events are related to loss of adequate appetite control. On the other hand, stress exposure also has important relation with food control. An important source of stress is maternal deprivation (MD) in the neonatal period, causing lifetime impacts. Animal studies have shown that stress induced by MD causes neurochemical changes. These changes have been related to mental disorders such as anxiety and depression, as well as obesity in adulthood. Considering the relevance of this topic, in this dissertation we evaluated the effect of MD in neonatal period and / or exposure to hypercaloric diet (condensed milk) after weaning on neuromotor, ponderal, behavioral and neurochemical development parameters in young adult male and female Wistar rats. Sixty-four male and female Wistar rats were distributed into four groups: Control (C) - without MD and exposed to the standard diet; Maternal Deprivation (MD) - animals submitted to MD (P1-P10) and exposed to the standard diet; Hypercaloric (HD) diet - without MD and exposed to the hypercaloric diet (palatable food / condensed milk); and Maternal Deprivation and Hypercaloric Diet (MDHD) - animals submitted to MD (P1-P10) and exposed to the hypercaloric diet (palatable food / condensed milk). The effects of MD on the initial reflex patterns in the pups were evaluated by the negative geotaxis and righting reflex tests, as well as their effects on the nociceptive response assessed by the Hot Plate (HP) and Tail-Flick tests (TFL). We also evaluated the anxiety-like behavior through the Elevated Plus-Maze (EPM) test and the locomotor activity by the Open Field Test (OF) before weaning (P21). From P21, the animals from the HD and MDHD groups were exposed to a hypercaloric / palatable diet (condensed milk) for three weeks and the nociceptive response, anxious-like behavior and locomotor activity were evaluated once again. We emphasize that the effect of gender in all parameters was analyzed. After the second set of behavioral tests, the animals were killed (P44) and the cerebral cortex, hippocampus and hypothalamus were removed for biochemical measurements. Levels of neuronal brain development factor (BDNF), neuronal growth factor 1 (NGF-1) and proinflammatory cytokines (IL6 and TNF-α) and anti-inflammatory cytokine (IL10) were measured. Our results demonstrate that the exposure to MD induces, in the short term, changes in the initial motor development, thermal nociceptive response (increase of the nociceptive threshold - PQ and TFL-females), increases locomotor activity of females due to the greater number of outter crossings and grooming time in males, which may be related to changes in dopaminergic system (OF test); increases time spent in open arms of deprived animals suggesting an anxiolytic effect of this intervention, increases the number of non-protected head dipping (NPHD) in males, behaviors related to exploratory activity and risk assessment (EPM test). The late effects of DM, evaluated between P42 and P43, were observed in the nociceptive response (decrease males’ nociceptive thresholds in the TFL) and in the EPM test males presented a greater number of rearings, indicative of an increase in exploratory activity dependent on gender. When exposed to HD, males showed greater weight gain and Lee index. HD induced an increase in the relative adipose tissue weight, regardless of sex. Late effects of MD and gender on the BDNF levels were observed in the brain structures evaluated. Effect of HD exposure was observed only on the hypothalamic levels of NGF-1. Females presented higher levels of BDNF and IL-6 in hippocampus and hypothalamus, and TNF-α in the hypothalamus. At cortical levels of IL-10 there was interaction between gender and MD. In conclusion, these findings contribute to a better understanding of the possible effects of early exposure to a stressor and / or palatable food in childhood / adolescence, demonstrating different responses according to gender to the proposed interventions. In addition, gender differences per se were observed, suggesting the importance of including both genders in preclinical investigations in order to bring greater translationality to the studies.