This study examined if multi-joint resistance exercises could elicit expression of biomarkers associated with neuroprotection. Thirteen well-trained males performed 4 sets to failure at 80% of a one-repetition maximum (1RM) on the back squat, bench press, and deadlift. The biomarkers measured immediately pre- and post-exercise were brain derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), cathepsin B (CatB), and interleukin 6 (IL-6). There was a main time effect (p<0.01) for BDNF with significant increases in the deadlift (p=0.01) and bench press (p=0.01) conditions, but not the squat (p=0.21). There was a main time effect (p<0.01) for IL-6 with a significant increase in the squat (p<0.01). There was no significant increase in CatB or IGF-1 (p>0.05). Additionally, there was no significant relationship between BDNF and IL-6 response. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

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.

Electroconvulsive therapy (ECT) is one of the oldest and most effective treatments for depression; however, its biological underpinnings are poorly understood. Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are two chemical messenger systems implicated in the antidepressant action and cognitive side effects of ECT. The Wistar-Kyoto (WKY) strain is a genetic model of depression that shows biological, cognitive, behavioural, and treatment-response abnormalities, making it potentially a useful model in which to investigate the underpinnings of the action of electroconvulsive stimulus (ECS: the amimal model of ECT). In addition, the WKY presents a potentially useful model for translational research on depression. The WKY strain is particularly valuable for the measurement of serum BDNF protein, for which the association with antidepressant treatments is much less clear (mostly stemming from investigations in humans) than that between brain BDNF and antidepressant treatments in rodent studies. The three studies presented add insight into the biological and behavioural effects of ECS. The first study (chapter 2) found no evidence of increased (R)-[11C]rolipram binding (an indirect marker of cyclic-adenosine monophosphate, cAMP) in the brain, despite significant increases of brain BDNF protein expression after repeated ECS. The second study (chapter 3) demonstrated the validity of the WKY strain in the investigation of ECS. Relative to Wistar controls, WKY showed similar antidepressant and cognitive effects (despite some abnormal behavioural responses), immediate but not sustained increases in brain BDNF protein, and a novel finding of increased extra-hypothalamic CRF after 5 daily ECS. The final study (chapter 4) demonstrated baseline strain differences in serum (WKY < Wistar) but not brain BDNF and, in both strains, no change in serum BDNF despite significant changes in brain BDNF after repeated ECS treatment. Preliminary results from a human pilot study investigating similar measures in a small group of people receiving ECT for depression are also presented. The results of this body of work advance our understanding of the activation and role of brain and serum measures of BDNF and the HPA axis in ECS/ECT, and raise important issues in the translation of research from basic science to the human condition of depression.

Electroconvulsive therapy (ECT) is one of the oldest and most effective treatments for depression; however, its biological underpinnings are poorly understood. Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are two chemical messenger systems implicated in the antidepressant action and cognitive side effects of ECT. The Wistar-Kyoto (WKY) strain is a genetic model of depression that shows biological, cognitive, behavioural, and treatment-response abnormalities, making it potentially a useful model in which to investigate the underpinnings of the action of electroconvulsive stimulus (ECS: the amimal model of ECT). In addition, the WKY presents a potentially useful model for translational research on depression. The WKY strain is particularly valuable for the measurement of serum BDNF protein, for which the association with antidepressant treatments is much less clear (mostly stemming from investigations in humans) than that between brain BDNF and antidepressant treatments in rodent studies. The three studies presented add insight into the biological and behavioural effects of ECS. The first study (chapter 2) found no evidence of increased (R)-[11C]rolipram binding (an indirect marker of cyclic-adenosine monophosphate, cAMP) in the brain, despite significant increases of brain BDNF protein expression after repeated ECS. The second study (chapter 3) demonstrated the validity of the WKY strain in the investigation of ECS. Relative to Wistar controls, WKY showed similar antidepressant and cognitive effects (despite some abnormal behavioural responses), immediate but not sustained increases in brain BDNF protein, and a novel finding of increased extra-hypothalamic CRF after 5 daily ECS. The final study (chapter 4) demonstrated baseline strain differences in serum (WKY < Wistar) but not brain BDNF and, in both strains, no change in serum BDNF despite significant changes in brain BDNF after repeated ECS treatment. Preliminary results from a human pilot study investigating similar measures in a small group of people receiving ECT for depression are also presented. The results of this body of work advance our understanding of the activation and role of brain and serum measures of BDNF and the HPA axis in ECS/ECT, and raise important issues in the translation of research from basic science to the human condition of depression.

This thesis presents the first randomised controlled trial (RCT) to investigate whether supplemented probiotic bacteria-"live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" (Sanders, 2008)-affect mood and other psychological outcomes in people presenting with low mood. Seventy-nine participants with at least moderate symptoms of depression were randomised in a double-blind manner to receive either a probiotic preparation containing Lactobacillus helveticus and Bifidobacterium longum or a matched placebo for eight weeks. The RCT phase was followed by an open label extension in which all participants were offered the active study product for a further 8 weeks. Participants were followed up at 6 months post-study. Based on the existing evidence from gut-brain axis research, and on models linking depression with inflammation, immune activation, low vitamin D levels, and the gut microbiota (outlined in Chapters 1 and 2), it was hypothesised that: the overall sample would have elevated levels of inflammatory biomarkers and low levels of vitamin D at baseline, and that this would be associated with scores on psychological and irritable bowel syndrome (IBS) outcome measures; that group differences (active treatment versus placebo) would be observed in scores on psychological outcome measures after eight weeks of probiotic intervention; that group differences would also be observed in blood levels of proinflammatory cytokines, hsCRP, vitamin D and BDNF, and scores on a measure of gut function/IBS, and that levels of these variables may predict or impact on treatment response; and that group differences would be observed on outcome measures at the point of the 6-month follow-up between those who continued to take the probiotic and those who discontinued probiotic use. In total, 58 of the 77 participants who provided baseline blood samples (75%) had at least one marker of inflammation elevated outside the normal reference range at baseline. Baseline vitamin D was approaching the deficient level, displayed a seasonal pattern, and was associated with severity on one measure of cognition. No significant differences were found between the active treatment and placebo groups on any psychological outcome measure, the measure of gut function or in the level of any blood-based biomarker in the randomised phase. Baseline vitamin D level was found to moderate treatment effect on several outcome measures. The results of the open label extension supported the lack of efficacy observed in the randomised phase, and also allowed for the comparison of efficacy over intervention periods of varying durations. The results of the follow-up at 6 months post-trial indicated that, while mean scores on psychological outcome measures remained lower than baseline, there was regression on some outcome measures after the study. When the participants who replied to the 6 month follow-up questionnaire were divided into groups based on their self-reported dominant treatment since the trial (probiotics/nutrition, standard treatment or no treatment) there was no difference in mood or other psychological outcomes among the groups at 6 months. The current trial found no evidence that this probiotic formulation is effective in treating the symptoms of depression or IBS, or in moderating the levels of inflammatory and other biomarkers in a sample recruited with moderate depression. This finding does not support the theory proposed in several narrative reviews which suggests probiotics as a possible intervention for depression and other mental health outcomes, but is supported by the systematic review of human probiotics studies presented in Chapter 3 which found overall limited evidence of probiotic efficacy for psychological outcomes. Future studies in the area should attempt to further broaden this field, in particular by recruiting samples with mild and/or non-chronic depression for interventional studies, or by approaching probiotics as a preventative or adjuvant treatment strategy for depression.

Older adults who stay physically and mentally active appear to have better cognitive function compared to their less active counterparts. In fact, those who perform either regular exercise or cognitive training (CT) can maintain and improve their cognitive functioning, even in their later years. Resistance training (RT) causes an increase in specific hormones that are responsible for improved brain functioning; however, many questions about how these hormones respond to RT are unanswered. Understanding how these hormones respond to RT can help researchers and clinicians create optimal training programs for older adults. Research shows that combining exercise and CT may be better for the brain compared to either activity performed alone; however, nobody has looked at RT combined with CT. We believe that combining RT and CT where CT is performed when an individual’s hormones are highest (right after RT) could have a big effect on brain function in a short period of time. This work represents a two-part study looked at: 1) how these hormones respond to a session of RT, and 2) the effect of combined RT and CT on cognitive function in older adults. Our participants performed CT immediately after RT, 3 times per week for 8 weeks. Specific hormones which are important for brain function were measured immediately before and for 2 hours after an acute bout of RT before and after 8-weeks of RT. Cognitive function was measured before and after the RT training period. Our primary findings were: 1) significant increases in brain derived neurotrophic factor immediately after RT and 2) participants cognitive function improved after 8 weeks of training. This is important because short-term combined RT and CT can lead to significant improvements in cognitive functioning. Also, this work will allow researchers to begin designing exercise programs that can maximize the brain’s ability to change, even at an old age. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2012-09-21 15:29:35.509

Electroconvulsive therapy (ECT) is one of the oldest and most effective treatments for depression; however, its biological underpinnings are poorly understood. Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are two chemical messenger systems implicated in the antidepressant action and cognitive side effects of ECT. The Wistar-Kyoto (WKY) strain is a genetic model of depression that shows biological, cognitive, behavioural, and treatment-response abnormalities, making it potentially a useful model in which to investigate the underpinnings of the action of electroconvulsive stimulus (ECS: the amimal model of ECT). In addition, the WKY presents a potentially useful model for translational research on depression. The WKY strain is particularly valuable for the measurement of serum BDNF protein, for which the association with antidepressant treatments is much less clear (mostly stemming from investigations in humans) than that between brain BDNF and antidepressant treatments in rodent studies. The three studies presented add insight into the biological and behavioural effects of ECS. The first study (chapter 2) found no evidence of increased (R)-[11C]rolipram binding (an indirect marker of cyclic-adenosine monophosphate, cAMP) in the brain, despite significant increases of brain BDNF protein expression after repeated ECS. The second study (chapter 3) demonstrated the validity of the WKY strain in the investigation of ECS. Relative to Wistar controls, WKY showed similar antidepressant and cognitive effects (despite some abnormal behavioural responses), immediate but not sustained increases in brain BDNF protein, and a novel finding of increased extra-hypothalamic CRF after 5 daily ECS. The final study (chapter 4) demonstrated baseline strain differences in serum (WKY < Wistar) but not brain BDNF and, in both strains, no change in serum BDNF despite significant changes in brain BDNF after repeated ECS treatment. Preliminary results from a human pilot study investigating similar measures in a small group of people receiving ECT for depression are also presented. The results of this body of work advance our understanding of the activation and role of brain and serum measures of BDNF and the HPA axis in ECS/ECT, and raise important issues in the translation of research from basic science to the human condition of depression.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 95-113).

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Sept. 16, 2008). Includes bibliographical references.

A prevalência de Doença Mental Grave (do inglês Severe Mental Illness, SMI) atinge 5,4% em um ano segundo os estudos Baltimore Epidemiologic Catchment Area e National Comorbidity Survey. O conceito de SMI surgiu na década de 1970 para o planejamento dos serviços de saúde e apresentou importância crescente a partir do movimento de desinstitucionalização psiquiátrica. Uma das definições para SMI deriva do NIMH (National Institute of Mental Health) em 1987, e utiliza como critérios a presença de prejuízo funcional, decorrente de déficits em aspectos básicos do dia-a-dia, bem como a duração da doença. Casos agudos de SMI podem necessitar tratamento em Unidade de Internação Psiquiátrica em Hospital Geral (UIPHG). No entanto, há poucos estudos disponíveis no Brasil avaliando esta modalidade de tratamento e os desfechos destes pacientes. Evidências também apontam que os pacientes com transtornos psiquiátricos apresentam níveis reduzidos de Fator Neurotrófico Derivado do Cérebro (Brain-Derived Neurotrophic Factor, BDNF). O BDNF age no sistema nervoso central (SNC) promovendo crescimento e diferenciação de neurônios. Dentro deste contexto, a presente tese apresenta como objetivo principal a avaliação naturalística de desfechos clínicos e funcionais, associados à avaliação dos níveis séricos de BDNF, em pacientes com SMI. Os pacientes que foram encaminhados para tratamento na Unidade de Internação Psiquiátrica do Hospital de Clínicas de Porto Alegre foram incluídos se apresentassem os critérios de SMI: Avaliação Global de Funcionamento (Global Assessment of Functioning, GAF) menor ou igual a 50 e tempo de tratamento maior ou igual a dois anos. As avaliações ocorreram em dois momentos (admissão e alta). Compreenderam avaliação sociodemográfica, clínica e coleta de sangue (com dosagem de BDNF sérico). Foram realizadas avaliação diagnóstica pelo Mini-International Neuropsychiatric Interview (MINI) e aplicação das escalas Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression scale (CGI-S), GAF e World Health Organization Quality of Life Instrument—Short Version (WHOQOL-Bref). Ainda, foram aplicadas escalas específicas nos diagnósticos principais (i.e., depressão maior, depressão bipolar, episódio maníaco, esquizofrenia): Hamilton Depression Rating Scale (HAM-D); Young Mania Rating Scale (YMRS). O primeiro artigo desta tese descreve os desfechos clínicos, funcionais e também de qualidade de vida durante a internação psiquiátrica. Observou-se melhora significativa nos parâmetros avaliados nos pacientes com SMI como um todo. Os pacientes com episódio maníaco apresentaram maior chance (em relação aos com episódio depressivo) de atingir remissão pela CGI (OR: 4.03; 95% CI: 1.14-14.30; p=0.03). A duração média da hospitalização (LOS) foi 28,95 (± 19,86) dias. No segundo artigo, observou-se redução dos níveis séricos de BDNF nos pacientes com SMI em relação aos controles saudáveis, independentemente do diagnóstico. Houve aumento significativo no BDNF entre a admissão e a alta. Os resultados apresentados replicam dados previamente publicados a partir de amostra única de pacientes com SMI, sua característica diferencial. Estes resultados reforçam que a internação em UIPHG, uma intervenção relativamente breve, demonstra desfechos positivos e é alternativa bem estabelecida no tratamento da SMI. Além disso, a redução inespecífica do BDNF sérico seguida de um pequeno aumento associado ao tratamento reforçam a possibilidade do BDNF como marcador transdiagnóstico de transtorno mental. / The estimated prevalence of Severe Mental Illness (SMI) according to Baltimore Epidemiologic Catchment Area and National Comorbidity Survey studies is 5.4% in one year. One suggested definition of Severe Mental Illness (SMI) derives from the 1987 National Institute of Mental Health (NIMH) definition and is based on two criteria: 1. duration, characterized as involving “prolonged illness”, and 2. disability, which includes dangerous or disturbing social behavior, and mild impairment in achieving basic needs. These acute psychiatric conditions may require psychiatric inpatient treatment located in acute wards in General Hospitals. However, little data is currently available evaluating the characteristics and the outcomes during an acute inpatient stay in Brazil. Evidence also suggests that Brain-derived neurotrophic factor (BDNF) levels are significantly decreased in neuropsychiatric disorders. BDNF is found throughout the brain and is involved in neurogenesis and neuroplasticity. So, the main objectives of this work are to evaluate SMI patients’ outcomes during treatment in a psychiatric unit in a general hospital by symptomatology, functionality, quality of life and by the evaluation of BDNF serum levels. After the admission to a psychiatric unit in a general hospital in Brazil, patients were included and if they had two of the SMI criteria: Global Assessment of Functioning (GAF) ≤ 50 and duration of services contact ≥ 2 years. Patients were assessed in admission and upon discharge with Mini-International Neuropsychiatric Interview (MINI), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression Scale (CGI), GAF, World Health Organization’s QOL Instrument—Short Version (WHOQOL-Bref) and diagnostic specific scales (Hamilton Depression Rating Scale, HAM-D; Young Mania Rating Scale, YMRS; and Hamilton Anxiety Rating Scale, HAM-A). Blood samples were also obtained. The first manuscript showed that SMI patients had marked and significant improvements in symptomatic and functional measures during psychiatric hospitalization. Patients with manic episode had higher chance of CGI remission (OR: 4.03; 95% CI: 1.14-14.30; p=0.03) when compared with patients with depressive episode. Mean LOS was 28.95 (± 19.86) days. The second manuscript showed that BDNF serum levels were equally reduced among different SMI diagnoses. Also, the observed improvements in SMI patients were associated with a significant, but small increase in mean serum BDNF levels. Therefore, the results replicate evidence from previous findings in single samples, suggesting that SMI patients can have marked acute improvements during a a relatively short intervention (approximately 1 month) represented by the psychiatric hospitalization in a general tertiary hospital. Also, the similar reduction observed in BDNF levels among SMI patients with different diagnoses and the significant increase but non-restoration indicate that BDNF serum levels could be considered a marker for the presence of an unspecific psychiatric disorder and possibly a transdiagnostic and unspecific marker of disease activity.