Orientador: Man Chin Chung / Coorientador: Carlos Cesar Crestani / Banca: Silvia Honda Takada / Banca: Ellen Cristini de Freitas / Banca: Priscila Longhin Bosquesi de Oliveira / Banca: Eduardo Rene Perez Gonzales / Resumo: O consumo excessivo de etanol está relacionado a diminuição da neurogênese hipocampal e a diversas patologias cardiovasculares, como a hipertensão. A taurina é um aminoácido não-essencial encontrado principalmente em estruturas cujos tecidos são mais excitáveis, como músculo esquelético, tecido cardíaco, vasos sanguíneos e sistema nervoso central. Níveis normais deste nutriente são essenciais para o correto funcionamento do organismo e sua depleção pode precipitar diversos quadros patológicos. A taurina tem apresentado resultados promissores tanto no sistema cardiovascular quanto no sistema nervoso central. Desta maneira, o objetivo deste trabalho foi estudar os efeitos da taurina na função cardiovascular bem como na neurogênese hipocampal de ratos submetidos ao modelo de consumo forçado de etanol. Dessa forma, ratos Wistar de aproximadamente 250 gramas receberam soluções crescentes de etanol (5% na primeira semana, 10% na segunda semana e 20% na terceira e quarta semana), sem a oferta de água; o grupo controle recebeu apenas água. A taurina foi administrada (i.p., 300 mg/kg) diariamente durante 28 dias e os animais do grupo controle receberam injeção apenas do veículo. O presente trabalho foi dividido em dois experimentos. No primeiro, a taurina foi administrada juntamente com a oferta de etanol. Já o segundo experimento, os animais foram expostos ao etanol e depois, receberam a taurina. Os resultados do Experimento 1 não mostraram alterações significativas na função cardiov... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Excessive ethanol consumption is related with decrease in hippocampal neurogenesis and various cardiovascular disorders such as hypertension. Taurine is a non-essential amino acid and is found primarily in structures which are more excitable tissues, such as skeletal muscle, heart tissue, blood vessels and central nervous system. Normal levels of this compound are essential for the correct functioning of the body and its depletion may precipitate various pathological conditions. Among the various compounds studied to reverse or protect against the effects of ethanol, taurine have shown promising results both in the cardiovascular system and the central nervous system. Thus, the objectives of this study was to investigate the effects of taurine on cardiovascular function and hippocampal neurogenesis in rats submitted to the model of forced consumption of ethanol. Wistar rats of 250g of body weight received ethanol solution (5% in the first week, 10% in the second week and 20% in the third and fourth week) without the offer of water. Taurine was administered (i.p., 300 mg / kg) daily for 28 days. This study was divided into two experiments. In the first one, to analyze the protective effects of taurine on the cardiovascular system and hippocampal neurogenesis against the effects of ethanol consumption, taurine was administered along with the ethanol consumption model. In the second experiment, to analyze the effects of taurine in reversing the effects of ethanol consumption, the animals were exposed to the ethanol consumption model and then received taurine. The results of Experiment 1 showed no significant changes in cardiovascular function... (Complete abstract click electronic access below) / Doutor

Lysosomal storage disorders (LSDs) comprise a broad disease group of inherited metabolic disorders, the majority of which are associated with CNS pathology, significant disability and reductions in life expectancy. LSDs are caused by mutations in genes encoding proteins critical for the correct functioning of lysosomal homeostasis. The disruption of lysosomal homeostasis results in the abnormal accumulation of lysosomal content, initiating intracellular pathological events, including calcium dysregulation and lysosomal membrane permeablisation (LMP) affecting cell function and inducing cellular death mechanisms. These pathological events are particularly damaging within the CNS, due to its limited capacity for regeneration. Despite intensive scientific research into these disorders, and an increased understanding of the pathological events underlying these diseases, effective treatments are still lacking for most LSDs. Several therapeutic approaches have been investigated in the last 30 years, including enzyme replacement therapy, bone marrow transplantation, substrate reduction therapy, chemical chaperones and gene therapy. However, the CNS pathology in many of the LSDs remains unaddressed due to the restricted ability of many therapeutic agents to cross the blood-brain barrier. The heat-shock response (HSR) is an emerging element involved in the pathogenesis of a variety of disorders. The HSR is a physiological response to a wide range of cellular stresses. It functions to protect the cell from the aggregation of misfolded proteins and LMP. Of the HSR, several key players are integral to mounting a heat shock response, these include the heat-shock factor 1 (HSF-1) and HSP70. In this thesis, we provide proof-of-principle for the use of recombinant HSP70, and the small molecule up-regulator of the HSR, arimoclomol in treatment of a range of LSDs. We show that HSP70 is able to access the CNS, and increase the degradative capacity of lysosomal hydrolases. This provides differential behavioural, biochemical and survival effects in LSD models of Niemann-Pick type C, Sandhoff and Fabry disease. Additional studies using the HSF-1 upregulator arimoclomol, show a complex dose-response between the different models, possibly reflecting essential differences in the calcium dysregulation between these disease states.

Caffeine consistently enhances endurance performance in temperate environmental conditions, while far less research has examined its ergogenic and physiological effects during prolonged exercise in the heat. Despite the performance benefit of an acute caffeine doses being less pronounced in regular caffeine users versus those not habituated to the drug, few studies have examined the influence of a prolonged period of controlled caffeine intake on endurance performance. The endogenous trace amine octopamine is purported to possess stimulant-like properties and influence fat metabolism, although no study has examined these effects in humans. The aim of this thesis was to further characterise the performance and physiological effects of caffeine during prolonged exercise, while elucidating a potential ergogenic role for octopamine. The first two studies investigated the ergogenic and thermoregulatory effects of low to moderate caffeine doses during prolonged cycle exercise in the heat. Chapter 4 demonstrated that 3 mg kg-1 caffeine, administered either as a single or split-dose (2 x 1.5 mg kg-1) before exercise, improved endurance performance without influencing thermoregulation during prolonged exercise at a fixed work-rate. Dividing the caffeine bolus appeared to confer an additional performance benefit, suggesting repeated low dose may potentiate the efficiency of the same total caffeine dose under these conditions. Chapter 5 demonstrated that a 6 mg kg-1 caffeine dose improved endurance cycle performance without differentially influencing thermoregulation than placebo. The level of habituation to caffeine influences the ergogenic effect of an acute dose, yet previous studies have employed sub-chronic supplementation protocols. Chapter 6 investigated the effect of a twenty-eight day supplementation period on endurance cycle performance. Habituation to caffeine attenuated the ergogenic effect of an acute caffeine dose, without any change in circulating caffeine, substrate oxidation or hormonal concentrations. In chapter 7 the performance and metabolic effects of octopamine was investigated. Octopamine supplementation did not influence performance, hormonal concentrations or substrate oxidation, likely due to low serum concentrations of the drug.

xiii, 104 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / Neurogenesis in Drosophila and mammals requires the precise integration of spatial and temporal cues. In Drosophila, embryonic neural progenitors, called neuroblasts, sequentially express the transcription factors Hunchback, Kruppel, Pdml/Pdm2 (Pdm) and Castor as they divide to generate a stereotyped sequence of neuronal and glial progeny. Hunchback is necessary and sufficient to specify the firstborn cell identity in many neuroblast lineages. Additionally, Hunchback is able to maintain an early-competence state in which early-born cells are generated. Furthermore, the Hunchback mammalian ortholog, Ikaros, possesses a similar ability to specify early- born cells in the vertebrate nervous system. However, the mechanisms underlying the function of Hunchback/Ikaros are unknown. Pdm and Castor are expressed later in many neuroblasts and can specify late-born neuronal cell identities in a model neuroblast lineage, NB7-1. Previous work studying their function in the NB7-1 lineage showed that Pdm and Castor act as repressors of Kruppel gene expression and inhibit the generation of the Kruppel-dependent cell identity. It is not known if the functions of Pdm and Castor are conserved across multiple neuroblast lineages during neurogenesis or whether these factors impart any restrictions on the ability of a factor like Hunchback to maintain early competence. To investigate the transcriptional mechanisms regulating early neuroblast competence in Drosophila, I have focused my dissertation research on two aims. The first is to examine the function of Pdm and Castor across multiple neuroblast lineages to characterize their potential roles as competence restricting factors; the second is to determine how Hunchback maintains early neuroblast competence and specifies early-born cell identities (e.g. as a transcriptional activator, repressor, or both). My work demonstrates that Pdm and Castor control the timing of Kruppel gene expression, and possibly the timing of other genes, in neuroblasts. Furthermore, I have shown that Hunchback acts as a transcriptional repressor of multiple target genes, including pdm and castor, to maintain early neuroblast competence. Because Hunchback must repress at least one additional unknown factor that can restrict neuroblast competence, I have piloted a screen to identify and characterize novel Hunchback target genes in the nervous system. This dissertation includes previously published and unpublished co-authored materials. / Committee in charge: Victoria Herman, Chairperson, Biology; Christopher Doe, Advisor, Biology; Judith Eisen, Advisor, Biology; Charles Kimmel, Member, Biology; Hui Zong, Member, Biology; Kenneth Prehoda, Outside Member, Chemistry

The present study aimed at investigating the neuropsychological sequelae of transient ischaemic attacks. Transient ischaemic attacks are defined as those neurological disorders in which there is complete resolution of neurological symptoms within twenty·four hours. Transient ischaemic attacks may or may not reveal evidence of brain infarcts on imaging studies. In the present study, the neuropsychological sequelae of transient ischaemic attacks in the carotid circulation were investigated since, within the perspective of cognitive neuropsychology, it was assumed that localized changes in cognitive functions could be demonstrated.Since several psychological, medical and neurological factors are known to influence scores·on neuropsychological tests, regression analyses were performed to determine which factors contributed significantly to the variance of scores on neuropsychological tests in the transient ischaemic attack and control groups. Two transient ischaemic attack groups, each comprising forty left and forty right hemisphere involvement patients, were then compared with each other and with a control group of forty general medical patients. Stenosis of the carotid artery formed a significant predictor of test scores in the combined transient ischaemic attack group. When the groups were·analyzed independently, in the left transient ischaemic attack group stenosis predicted performance on the same tests reaching significance for the combined group, and for the Wisconsin Card Sorting Test (Perseverative Score). In the right transient ischaemic attack group, stenosis significantly predicted performance on Digits Forward, Backward and Total, the PASAT (2.4 seconds) and Trails B. On the other hand, education formed a significant predictor of performance on Digits Forward, Digits Backward and Digits Total and the PASAT (all levels) in the control group. Multivariate comparisons revealed that the left and right transient ischaemic attack groups performed worse than the controls on tests of attention, concentration and conceptual flexibi1ity. The left transient ischaemic attack group performed worse than the right transient ischaemic attack group on all tests of attention and concentration, but there was a significantly better performance of the former group on the Rey Auditory Verbal Learning Test (Trial 1), Block Designs and Verbal Fluency. The findings on the PASAT that left transient ischaemic attack patients performed significantly worse than the right hemisphere group ·were considered to be relatively unreported previously in the literature on transient ischaemic attacks. The findings obtained are discussed from a neurocognitive perspective of neuropsychological functioning in transient ischaemic attacks. / Psychology / Ph. D. (Psychology)

Made available in DSpace on 2015-12-10T14:22:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-07-31. Added 1 bitstream(s) on 2015-12-10T14:29:07Z : No. of bitstreams: 1 000853245.pdf: 5848716 bytes, checksum: 9fb857dfa29e26d6bcd61db677d6bdc7 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Os neurônios da raiz coclear (CRN) são os primeiros neurônios do sistema nervoso central a receber a informação auditiva e conectam-se com centros de integração sensoriomotora do tronco encefálico, como o núcleo reticular caudal da ponte. Os CRN estão envolvidos no circuito elementar do reflexo auditivo de sobressalto (RAS) juntamente com os neurônios do gânglio espiral, o núcleo reticular caudal da ponte e os motoneurônios da medula espinal. O RAS apresenta uma série de modulações como a habituação, a sensibilização, a potenciação por um estímulo adverso e a inibição por estímulo prévio (PPI). As modulações do RAS ocorrem mediante a influência de diversos núcleos sobre os componentes do circuito elementar deste reflexo e possuem valor diagnóstico na clinica médica de enfermidades neurodegenerativas e psiquiátricas como Parkinson e esquizofrenia. O núcleo da raiz coclear é o menos estudado do circuito neural do RAS. Pouco se conhece sobre as origens das aferências aos CRN e a identidade neuroquímica das mesmas. Recentemente foi descrita uma nova fonte de aferências aos neurônios da raiz coclear, de natureza colinérgica e proveniente do núcleo ventral do corpo trapezóide (VNTB). Os neurônios deste núcleo recebem informação auditiva diretamente do colículo inferior que faz parte da via auditiva e também participa do circuito neuronal responsável por mediar a PPI. Acredita-se que o colículo inferior possa mediar a PPI também ao nível do núcleo da raiz coclear via a conexão com o VNTB, o que constituiria uma via descentente curta, com participação na PPI com intervalos interestímulos curtos. Contudo, não existem estudos a respeito de aspectos funcionais desta conexão. Neste trabalho estudamos o papel da projeção colinérgica proveniente do VNTB através da lesão seletiva deste núcleo e avaliação comportamental do RAS e da PPI. Para isto realizamos 3 grupos experimentais: Controle... / The cochlear root neurons (CRN) are the first in the central nervous system to receive the acoustic information. They are in connection with sensory integration centers in the brainstem, particularly the pontine caudal nucleus. The CRN are related with the fundamental neural circuit of the acoustic startle reflex, together with the spiral ganglion neurons, the pontine reticular nucleus and the spinal cord motoneurons. The acoustic startle reflex shows various modulations such as habituation, sensitization, fear potentiation and prepulse inhibition. The modulations of the acoustic startle reflex are important in clinical diagnostics of psychiatric and neurodegenerative illnesses such as schizophrenia and Parkinson's disease. Startle modulations are promoted by influences from several nuclei on the fundamental neural circuit of the startle reflex. The cochlear root nucleus is the least studied nucleus of this circuit. The origins of the afferents to cochlear root neurons and its neurochemical identity remain unclear. Recently was described a new source of afferents to cochlear root neurons, cholinergic and coming from the ventral nucleus of the trapezoid body (VNTB). The neurons of this nucleus receive auditory information directly from the inferior colliculus which take part of the auditory pathway and also participates in the neural circuitry responsible for mediating the prepulse inhibition. Therefore, the inferior colliculus may mediate the prepulse inhibition at the cochlear root level via ventral nucleus of the trapezoid body connection, which would be a short and low latency pathway. However, there are no studies on functional aspects of this connection. We intend to study the role of cholinergic projections from the ventral nucleus of the trapezoid body by selective lesion of this nucleus and behavioral assessment of auditory startle reflex and prepulse inhibition. To achieve the purpose we proposed 3 experimental groups: Control ... / FAPESP: 2013/25737-6

Made available in DSpace on 2016-02-05T18:29:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-08-20. Added 1 bitstream(s) on 2016-02-05T18:33:46Z : No. of bitstreams: 1 000855110_20160820.pdf: 664562 bytes, checksum: b100e2fbde17c774255b11fd563661ba (MD5) Bitstreams deleted on 2016-08-22T16:41:54Z: 000855110_20160820.pdf,. Added 1 bitstream(s) on 2016-08-22T16:42:31Z : No. of bitstreams: 1 000855110.pdf: 1362897 bytes, checksum: 814c66d0d4dd13dba974090ba33240c7 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Os meningiomas são os tumores mais frequentes do Sistema Nervoso Central e sua classificação é dada quanto ao tipo celular envolvido e grau de malignidade. Os intérferons (IFNs) foram inicialmente associados à resposta antiviral, contudo, estudos posteriores evidenciaram o envolvimento dessas citocinas na regulação do crescimento celular e no efeito imunomodulatório. A Interleucina 28B (IL28B), membro da família dos IFNs do tipo III, parece estar envolvida na resposta imune antiviral e antitumoral. Sendo assim, o objetivo do presente estudo foi avaliar a frequência de variações genéticas em IL28B e IL28R1 em pacientes acometidos por Meningiomas. Sessenta paciente tratados pelo serviço de Neurocirurgia da UNESP de Botucatu/SP foram incluídos neste estudo. A análise do polimorfismo rs12979860 C/T teve significância estatística quando comparou-se a frequência genotípica da população brasileira em relação a presente casuística. Foi descrito a detecção de novas variações genéticas (missense e silent) nos genes IL28B e IL28R1 ao comparar com as respectivas sequencias referencias disponíveis em banco de dados (NCBI). Estes dados sugerem uma importante relação destas variações genéticas em relação a estrutura e função das proteínas envolvidas, entretanto um estudo mais aprofundado das consequências dessas alterações na gênese e/ou progressão dos meningiomas devem ser considerado / Meningiomas are the most common tumors of the central nervous system, despite being benign and grow slowly, can recur in case of incomplete surgical resection. They are classified according to the cells involved and their rate of malignancy. The role of the immune system in preventing the emergence and progression of tumors has been the subject of many studies in the field of tumor immunology. Interferon (IFNs) were originally associated with antiviral response, however, subsequent studies revealed the involvement of these cytokines in the regulation of cell growth and their immunomodulatory effect.Thus, the aim of this study was to analyze the genetic variation frequency of IL28B and IL28R1 in patients with meningioma. Sixty patients treated by UNESP Neurosurgery service of Botucatu/SP were included in this study. Polymorphism rs12979860 C/T analysis showed statistical significance when compared with healthy Brazilian's genotypic frequency. New genetic variation (missense and silent) were detected in IL28B and IL28R1 through reference sequences analysis (NCBI). These data support an important relation of these genetic variations related to protein functions, however other studies of the consequences of these changes in the development and progression of meningiomas should be considered

Le but de ce travail est de simuler des situations d'exposition radar en condition infrathermique pouvant être rencontrées sur les bâtiments de la Marine Nationale. Les expositions des personnels servant à bord de ces navires peuvent être ponctuelles ou prolongées selon les situations et les postes tenus. Il était nécessaire de rechercher leurs éventuels effets biologiques afin de contribuer à l'évaluation des risques sanitaires possibles liés à de telles expositions professionnelles et d'anticiper la survenue de contentieux. Nous avons examiné sur les effets d'ondes électromagnétiques impulsionnelles de forte puissance de type radar à la fréquence de 3 GHz sur un modèle rongeur. Les effets de plusieurs types d'exposition in vivo – aiguë (DAS 5 W/kg), semi-chronique (DAS 15 W/kg) et semi-chronique combinée à des expositions aiguës (mixte) - ont été étudiés chez le rat mâle adulte vigile à différents délais post-exposition (court, moyen et long terme). La dosimétrie a été réalisée de manière numérique (méthode FDTD) et expérimentale. Cette étude porte sur le système nerveux central, en particulier sur l'intégrité des fonctions cognitives et du tissu cérébral incluant la barrière hémato-encéphalique (BHE) et l'apoptose. Les capacités cognitives concernant la mémorisation, l'apprentissage, l'anxiété, l'agressivité et la motricité des animaux ont été testées. Des paramètres cliniques ont été observés régulièrement comme la prise de poids, la recherche de symptômes anormaux, notamment l'apparition de tumeurs avec prélèvement systématique et examen anatomopathologique. En complément, des analyses sanguines (NFS), un typage lymphocytaire et, dans certains cas, le dosage d'hormones de stress (ACTH et corticosterone) ont été réalisés. Aucun effet infrathermique de l'exposition aiguë à court terme n'a été observé sur l'intégrité de la BHE et sur l'apoptose cérébrale. Les résultats des tests comportementaux ne montrent aucune modification significative des fonctions cognitives relatives à la mémorisation, l'apprentissage, l'anxiété, l'agressivité, l'état neurologique global et à la motricité. Globalement, ces résultats n'indiquent pas d'effet sur le fonctionnement du système nerveux central dans les conditions expérimentales étudiées. Aucun effet statistiquement significatif n'a été mis en évidence sur le gain de poids relatifs des animaux après exposition infrathermique de type radar. Les résultats des analyses hématologiques, immunologiques, neuroendocriniennes de gestion du stress et du développement tumoral n'ont pas permis de retenir un effet infrathermique de l'exposition dans les conditions expérimentales étudiées. / The aim of this work was to simulate human exposure to high power pulsed microwave (HPM) emitted by radars of the French Navy. Navy staff exposure to radars may be occasional, prolonged or repeated depending on activities aboard. It was necessary to investigate their potential health effects in order to contribute to the risk assessment and anticipate potential litigation. A special emitting experimental device was developed in order to reproduce different exposure conditions at 3 GHz with an experimental model of adult rat. We present here the in vivo results obtained after 3 GHz exposure under non thermal conditions - acute (DAS 5 W/kg), chronic (DAS 15 W/kg) and chronic associated with repeated acute exposure (mixed) –for short, middle and long term effects on adult rat. The dosimetry was obtained by numerical simulation (FDTD) and completed with experimental measurements. Parameters related to the central nervous system, especially on blood brain barrier (BBB) and apoptosis were observed. The effects on cognitive function were assessed by different types of behavioral tests on memory, learning, anxiety, aggressiveness and locomotion of adult rat. Regular body weighing and clinical check-up including tumor incidence with sampling and histological examination were performed on rats. In parallel, hematological parameters were examined with complete blood count and immunological system was studied. The endocrine pathway involved in stress management have been studied through adrenocorticotrope hormone (ACTH) and corticosterone assays. No significant behavioral effect either on memory, learning, anxiety, aggressiveness, overall neurological evaluation either or on locomotion of adult rat. Results did not show any effect on central nervous system in our experimental conditions. No significant effect was observed on weight gain of rats after non thermal microwave exposure. Results on hematological parameters, on immunological parameters, on stress hormones and on tumors development did not detected any non thermal effect in our experimental conditions

Made available in DSpace on 2014-10-09T12:32:18Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:09:39Z (GMT). No. of bitstreams: 1 02362.pdf: 2112291 bytes, checksum: 2a220dd8c9f2bb4f20e848171ea39b0b (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Made available in DSpace on 2016-06-07T17:12:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-12. Added 1 bitstream(s) on 2016-06-07T17:16:34Z : No. of bitstreams: 1 000865904.pdf: 3145062 bytes, checksum: eeba3b59a5e1c3a2193bcb94a8b2cb0c (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / As anomalias craniofaciais são alterações do desenvolvimento do crânio e da face que podem ou não estar acompanhadas de malformações estruturais e/ou funcionais do SNC. Estas representam a quarta causa mais frequente dentre as anomalias congênitas em recém-nascidos, determinando, a seus portadores, prognóstico reservado na maioria das vezes. A holoprosecefalia é uma malformação do sistema nervoso central devido uma falha na divisão dos hemisférios direto e esquerdo do cérebro. Sabe-se que sua etiologia é múltipla e complexa. O fenótipo da HPE é bastante variável abrangendo um espectro contínuo desde manifestações graves envolvendo anomalias do cérebro e face até indivíduos clinicamente normais. Evidências genéticas são apresentadas todo ano por diversos grupos que estudam holoprosencefalia e a correlação genótipo/fenótipo continua sendo um desafio para os geneticistas. No presente estudo analisamos 124 amostras de DNA de indivíduos com diagnóstico clínico de holoprosencefalia. Todas as amostras de DNA foram submetidas a análise molecular através da técnica MLPA (SALSA® MLPA® KIT P187-B1 Holoprosencephaly e o SALSA® MLPA® KIT P036- E1 Human-telomere-3). Nesta análise, identificamos deleções/duplicações nos genes já descritos para HPE, sendo: três deleções no gene SHH, uma deleção no gene TGIF e uma duplicação no gene ZIC2. Dentre as 124 amostras, 26 foram selecionadas para análise por arrayCGH, o que permitiu a identificação de microdeleções/microduplicações em novas regiões cromossômicas, sendo elas: 2p25.2- p25.1, 2p21, 8p23.2, 10p15.3, 13q14.2 e Xq13.3. A utilização de MLPA e arrayCGH tem sido utilizada na pesquisa da etiologia de HPE, desde modo destacamos a eficiência destas técnicas, uma vez que metodologia utilizada neste estudo permitiu a identificação de deleções/duplicações cromossômicas nos indivíduos estudados, corroborando com a literatura e destacando... / Craniofacial anomalies are skull development changes and face that may or may not be accompanied by structural malformations and / or functional CNS. These represent the fourth most common cause among the congenital anomalies in newborns, determining, among the patients, poor prognosis in most cases. Holoprosecephaly is a malformation of the central nervous system due to a fault in the division of right and left hemispheres of the brain. It is known that the etiology is multiple and complex. The HPE phenotype is variable including a continuous spectrum from severe manifestations involving abnormalities of the brain and face to clinically normal individuals. Genetics evidences are presented every year by groups studying holoprosencephaly and the genotype/phenotype remains a challenge for geneticists. We analyzed ADN samples from 124 patients with clinical diagnosis for holoprosencephaly. All ADNs samples were subjected to molecular analysis by MLPA technique ( SALSA® MLPA® KIT -B1 holoprosencephaly P187 and P036 SALSA® MLPA® KIT - Human telomere -E1 -3). Thus, we identified deletions / duplications in genes already described for HPE, such as: three deletions in the SHH gene, one deletion of the TGIF gene and one duplication in ZIC2 gene. Among the 124 samples, 26 ADN samples were selected for analysis by arrayCGH allowing the identification of microdeletions/microduplications in new chromosomal regions: 2p25.2 - p25.1, 2p21, 8p23.2, 10p15.3, 13q14.2 and Xq13.3. MLPA and arrayCGH are often used in research on the etiology of HPE, in that way the efficiency of these techniques, since the methodology used in this study allowed the identification of deletions / duplications in chromosome individuals studied, corroborating the literature and identinfy new chromosomal regions to be elucidated to understand the etiology of this disease / FAPESP: 10/18740-2