THE ORGANIZATION OF THE NERVOUS-SYSTEM IN PLATHELMINTHES - THE NEUROPEPTIDE F-IMMUNOREACTIVE PATTERN IN CATENULIDA, MACROSTOMIDA, PROSERIATA

The organization of the nervous system of Archilopsis unipunctata Promonotus schultzei and Paramonotus hamatus (Monocelididae, Proseriata) and Stenostomum leucops (Catenulida) and Microstomum lineare (Macrostomida) was studied by immunocytochemistry, using antibodies to the authentic flatworm neuropeptide F (NPF) (Moniezia expansa). The organization of the nervous system of the Monocelididae was compared to that of the nervous system of Bothriomolus balticus (Otoplanidae), a previously studied species of another family of the Proseriata. The results show that the main nerve cords (MCs), independent of lateral or ventral position in the Monocelididae and the Otoplanidae, correspond to each other. The study also confirms the status of the lateral cords as main cords (MCs) in S. leucops and M. lineare. Common for MCs in the members of the investigated taxa are the following features: MCs consist of many fibres, originate from the brain and are adjoined to 5-HT-positive neurons. In Monocelididae and Otoplanidae, the MCs additionally have the same type of contact to the pharyngeal nervous system. Also common for both proseriate families is the organization of the two lateral nerve cords, with weaker connections to the brain, and the pair of dorsal cords running above the brain. The organization of the minor cords differs. The Monocelididae have a pair of thin ventral cords forming a mirror image of the dorsal pair. Furthermore, an unpaired ventral medial cord connecting medial commissural cells was observed in P. schultzei. Marginal nerve cords, observed in Otoplanidae, are absent in Monocelididae. All minor nerve cords are closely connected to the peripheral nerve plexus. The postulated trends of condensation of plexal fibres to cords and/or the flexibility of the peripheral nerve plexus are discussed. In addition, the immunoreactivity (IR) pattern of NPF was compared to the IR patterns of the neuropeptide RFamide and the indoleamine, 5-HT (serotonin). Significant differences between the distribution of IR to NPF and to 5-HT occur. 5-HT-IR dominates in the submuscular and subepidermal plexuses. In the stomatogastric plexus of M. lineare, only peptidergic IR is observed in the intestinal nerve net. The distribution of NPF-IR in fibres and cells of the intestinal wall in M. lineare indicates a regulatory function for this peptide in the gut, while a relationship with ciliary and muscular locomotion is suggested for the 5-HT-IR occurring in the subepidermal and submuscular nerve plexuses. In M. lineare, the study revealed an NPF- and RFamide-positive cell pair, marking the finished development of new zooids. This finding indicates that constancy of these cells is maintained in this asexually reproducing and regenerating species.

Clinical practice with anti-dementia drugs:a revised (second) consensus statement from the British Association for Psychopharmacology

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive improvements in DLB (A). There is no clear evidence that any intervention can prevent or delay the onset of dementia. Although the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition are in progress. Although results of pivotal studies are awaited, results to date have been equivocal and no disease-modifying agents are either licensed or can be currently recommended for clinical use.

Antenatal depression and anxiety affect postpartum parenting stress:a longitudinal, prospective study

Postpartum depression has been associated with parenting stress, impacting attachment and child development. However, the relation between antenatal depression or anxiety and postpartum parenting stress has not been investigated. We studied the effect of antenatal depression and anxiety and treatment with selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors (antidepressants [ADs]) on postpartum parenting stress.

Addressing Selective Polypharmacology of Antipsychotic Drugs Targeting the Bioaminergic Receptors through the Receptor Dynamic Conformational Ensembles

Selective polypharmacology, where a drug acts on multiple rather than single molecular targets involved in a disease, emerges to develop a structure-based system biology approach to design drugs selectively targeting a disease-active protein network. We focus on the bioaminergic receptors that belong to the group of integral membrane signalling proteins coupled to the G protein and represent targets for therapeutic agents against schizophrenia and depression. Among them, it has been shown that the serotonin (5-HT2A and 5-HT6), dopamine (D2 and D3) receptors induce a cognition-enhancing effect (group 1), while the histamine (H1) and serotonin (5-HT2C) receptors lead to metabolic side effects and the 5-HT2B serotonin receptor causes pulmonary hypertension (group 2). Thus, the problem arises to develop an approach that allows identifying drugs targeting only the disease-active receptors, i.e. group 1. The recent release of several crystal structures of the bioaminergic receptors, involving the D3 and H1 receptors provides the possibility to model the structures of all receptors and initiate a study of the structural and dynamic context of selective polypharmacology. In this work, we use molecular dynamics simulations to generate a conformational space of the receptors and subsequently characterize its binding properties applying molecular probe mapping. All-against-all comparison of the generated probe maps of the selected diverse conformations of all receptors with the Tanimoto similarity coefficient (Tc) enable to separate the receptors of group 1 from group 2. The pharmacophore built based on the Tc-selected receptor conformations, using the multiple probe maps discovers structural features that can be used to design molecules selective towards the receptors of group 1. The importance of several predicted residues to ligand selectivity is supported by the available mutagenesis and ligand structure-activity relationships studies. In addition, the Tc-selected conformations of the receptors for group 1 show good performance in isolation of known ligands from a random decoy. Our computational structure-based protocol to tackle selective polypharmacology of antipsychotic drugs could be applied for other diseases involving multiple drug targets, such as oncologic and infectious disorders.

Pharmacological studies of 8-OH-DPAT-induced pupillary dilation in anesthetized rats

Serotonin (5-HT) receptor agonists have been reported to produce mydriasis in mice, and miosis in rabbits and humans. However, the underlying mechanisms for this action are unclear. This study was undertaken in an attempt to explore the mechanism by which 5-HT receptors are involved in the modulation of pupillary size in pentobarbital-anesthetized rats. Intravenous administration of the 5-HT receptor agonist, (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.003-3 mg/kg), elicited dose-dependent pupillary dilation, which was not affected by section of the preganglionic cervical sympathetic nerve. 8-OH-DPAT-elicited mydriatic responses were attenuated by the selective 5-HT receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2- pyridinylcyclohexanecarboxamide maleate (WAY 100635; 0.3-1 mg/kg, i.v.), as well as by the selective a -adrenoceptor antagonist, (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a-dechydro-3-methoxy-12- (ethylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine hydrochloride (RS 79948; 0.3 mg/kg, i.v.), but not by the selective a -adrenoceptor antagonist, prazosin (0.3 mg/kg, i.v.). Mydriatic responses elicited by the a -adrenoceptor agonist, guanabenz (0.003-0.3 mg/kg, i.v.), were not antagonized by WAY 100635 (0.3-1 mg/kg, i.v.). To determine whether central nervous system (CNS) 5-HT receptors, like a -adrenoceptors, are involved in reflex mydriasis, voltage response curves of pupillary dilation were constructed by stimulation of the sciatic nerve in anesthetized rats. WAY 100635 (1 mg/kg, i.v.) did not antagonize the evoked reflex mydriasis, which, however, was blocked by RS 79948 (0.3 mg/kg, i.v.). Taken together, these results suggest that 8-OH-DPAT produces pupillary dilation in anesthetized rats by stimulating CNS 5-HT receptors, which in turn trigger the release of norepinephrine, presumably from the locus coeruleus. The latter reduces parasympathetic neuronal tone to the iris sphincter muscle by stimulation of postsynaptic a - adrenoceptors within the Edinger-Westphal nucleus. Unlike a - adrenoceptors, 5-HT receptors in the CNS do not mediate reflex mydriasis evoked by sciatic nerve stimulation. © 2004 Elsevier B.V. All rights reserved.

Clinical features of psychotic disorders and polymorphisms in HT2A, DRD2, DRD4, SLC6A3 (DAT1), and BDNF:a family based association study

Schizophrenia is clinically heterogeneous and multidimensional, but it is not known whether this is due to etiological heterogeneity. Previous studies have not consistently reported association between any specific polymorphisms and clinical features of schizophrenia, and have primarily used case-control designs. We tested for the presence of association between clinical features and polymorphisms in the genes for the serotonin 2A receptor (HT2A), dopamine receptor types 2 and 4, dopamine transporter (SLC6A3), and brain-derived neurotrophic factor (BDNF). Two hundred seventy pedigrees were ascertained on the basis of having two or more members with schizophrenia or poor outcome schizoaffective disorder. Diagnoses were made using a structured interview based on the SCID. All patients were rated on the major symptoms of schizophrenia scale (MSSS), integrating clinical and course features throughout the course of illness. Factor analysis revealed positive, negative, and affective symptom factors. The program QTDT was used to implement a family-based test of association for quantitative traits, controlling for age and sex. We found suggestive evidence of association between the His452Tyr polymorphism in HT2A and affective symptoms (P = 0.02), the 172-bp allele of BDNF and negative symptoms (P = 0.04), and the 480-bp allele in SLC6A3 (= DAT1) and negative symptoms (P = 0.04). As total of 19 alleles were tested, we cannot rule out false positives. However, given prior evidence of involvement of the proteins encoded by these genes in psychopathology, our results suggest that more attention should be focused on the impact of these alleles on clinical features of schizophrenia.

Electrochemical sensor for catechol and dopamine based on a catalytic molecularly imprinted polymer-conducting polymer hybrid recognition element

One of the difficulties with using molecularly imprinted polymers (MIPs) and other electrically insulating materials as the recognition element in electrochemical sensors is the lack of a direct path for the conduction of electrons from the active sites to the electrode. We have sought to address this problem through the preparation and characterization of novel hybrid materials combining a catalytic MIP, capable of oxidizing the template, catechol, with an electrically conducting polymer. In this way a network of "molecular wires" assists in the conduction of electrons from the active sites within the MIP to the electrode surface. This was made possible by the design of a new monomer that combines orthogonal polymerizable functionality; comprising an aniline group and a methacrylamide. Conducting films were prepared on the surface of electrodes (Au on glass) by electropolymerization of the aniline moiety. A layer of MIP was photochemically grafted over the polyaniline, via N,N'-diethyldithiocarbamic acid benzyl ester (iniferter) activation of the methacrylamide groups. Detection of catechol by the hybrid-MIP sensor was found to be specific, and catechol oxidation was detected by cyclic voltammetry at the optimized operating conditions: potential range -0.6 V to +0.8 V (vs Ag/AgCl), scan rate 50 mV/s, PBS pH 7.4. The calibration curve for catechol was found to be linear to 144 µM, with a limit of detection of 228 nM. Catechol and dopamine were detected by the sensor, whereas analogues and potentially interfering compounds, including phenol, resorcinol, hydroquinone, serotonin, and ascorbic acid, had minimal effect (=3%) on the detection of either analyte. Nonimprinted hybrid electrodes and bare gold electrodes failed to give any response to catechol at concentrations below 0.5 mM. Finally, the catalytic properties of the sensor were characterized by chronoamperometry and were found to be consistent with Michaelis-Menten kinetics. © 2009 American Chemical Society.

Neuromusculature of Gyrodactylus rysavyi, a monogenean gill and skin parasite of the catfish Clarias gariepinus

Phalloidin fluorescence technique, enzyme cytochemistry and immunocytochemistry in conjunction with confocal scanning laser microscopy were used for the first time to describe the nervous and muscle systems of the viviparous monogenean parasite, Gyrodactylus rysavyi inhabiting the gills and skin of the Nile catfish Clarias gariepinus. The body wall muscles are composed of an outer layer of circular fibres, an intermediate layer of paired longitudinal fibres and an inner layer of well-spaced bands of diagonal fibres arranged in two crossed directions. The musculature of the pharynx, intestine, reproductive tract and the most prominent muscles of the haptor were also described. Two characteristic muscular pads were found lying in the anterior region of the haptor in close contact with the hamuli. To each one of these pads, a group of ventral extrinsic muscles was connected. The role of this ventral extrinsic muscle in the body movement was discussed. The mechanism operating the marginal hooklets was also discussed. The central nervous system (CNS) consists of paired cerebral ganglia from which three pairs of longitudinal ventral, lateral and dorsal nerve cords arise. The nerve cords are connected at intervals by many transverse connectives. The CNS is better developed ventrally than dorsally or laterally and it has the highest reactivity for all neuroactive substances examined. Both the central and the peripheral nervous system (PNS) are bilaterally symmetrical. Structural and functional correlates of the neuromusculature of the pharynx, haptor and reproductive tracts were explained. The results implicated acetylcholine, FMRFamide-related peptides (FaRPs) and serotonin in sensory and motor function. The results were compared with those of the monogeneans Macrogyrodactylus clarii and M. congolensis inhabiting the gills and skin respectively of the same host fish C. gariepinus.

Neuromusculature of Macrogyrodactylus congolensis, a monogenean skin parasite of the Nile catfish Clarias gariepinus

Phalloidin fluorescence technique, enzyme cytochemistry and immunocytochemistry, in conjunction with confocal scanning laser microscopy, were used to describe the neuromusculature of the monogenean skin parasite Macrogyrodactylus congolensis from the Nile catfish Clarias gariepinus. The body wall muscles are composed of an outer layer of compactly arranged circular fibres, an intermediate layer of paired longitudinal fibres and an inner layer of well-spaced bands of diagonal fibres arranged in two crossed directions. The central nervous system consists of paired cerebral ganglia from which three pairs of longitudinal ventral, lateral and dorsal nerve cords arise. The nerve cords are connected at intervals by many transverse connectives. Both central and peripheral nervous systems are bilaterally symmetrical and better developed ventrally than laterally and dorsally. Structural and functional correlates of the neuromusculature of the pharynx, haptor and reproductive tracts were examined. Results implicate acetylcholine, FMRFamide-related peptides and serotonin in sensory and motor function. The results were compared with those of Macrogyrodactylus clarii, a gill parasite of the same host fish C. gariepinus.

Neuromusculature of Macrogyrodactylus clarii, a monogenean gill parasite of the Nile catfish Clarias gariepinus in Egypt

Phalloidin fluorescence technique, enzyme cytochemistry and immunocytochemistry in conjunction with confocal scanning laser microscopy have been used for the first time to describe the nervous and muscle systems of the viviparous monogenean gill parasite, Macrogyrodactylus clarii. The gross spatial arrangement of muscle and associated cholinergic, peptidergic and aminergic innervations has been examined. The central nervous system (CNS) consists of paired cerebral ganglia from which emanate three pairs of longitudinal ventral, lateral and dorsal nerve cords, connected at intervals by transverse connectives. The CNS is better developed ventrally than dorsally or laterally, and has the strongest reactivity for all neuroactive substances examined. Structural and functional correlates of the neuromusculature of the pharynx, haptor and reproductive tracts have been examined. Results implicate acetylcholine, FMRFamide-related peptides (FaRPs) and serotonin in sensory and motor function in this monogenean, although confirmatory physiological data are obviously required.

Alzheimer's disease-like pathology has transient effects on the brain and blood metabolome

The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology impacts upon the metabolome is still not understood, nor is it known how disturbances change as the disease progresses. For the first time we have profiled longitudinally (6, 8, 10, 12 and 18 months) both the brain and plasma metabolome of APP/PS1 double transgenic and wild type (WT) mice. A total of 187 metabolites were quantified using a targeted metabolomics methodology. Multivariate statistical analysis produced models that distinguished APP/PS1 from WT mice at 8, 10 and 12 months.Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids,branched chain amino acids and also in the neurotransmitter serotonin.Pronounced imbalances in phospholipid and acylcarnitine homeostasis was evident in two age groups. AD-like pathology therefore impacts greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood.

Morphological and ecological studies on the phylum Cycliophora

Cycliophora é um filo animal descrito recentemente que acomoda, apenas, duas espécies: Symbion pandora Funch e Kristensen, 1995 e S. americanus Obst, Funch e Kristensen, 2006. Este filo é caracterizado por um ciclo de vida assaz complexo, cuja posição filogenética tem sido debatida desde a sua descoberta. Esta dissertação visa aprofundar o conhecimento geral existente acerca destes enigmáticos e pouco explorados metazoários. Assim, vários aspectos da morfologia e ecologia de ciclióforos foram estudados através de observações in vivo, técnicas de microscopia e reconstrução tridimensional. A mioanatomia de várias fases do ciclo de vida é descrita para S. pandora e S. americanus. Os nossos resultados revelam uma similaridade contundente entre a musculatura das duas espécies. A mioanatomia geral de Symbion é, ainda, comparada à de outros metazoários. A expressão de algumas substâncias imunorreactivas, como são exemplo a serotonina e as sinapsinas, é investigada em várias formas do ciclo de vida. Quando comparados com outros representantes de Spiralia, conclui-se que a neuroanatomia geral dos ciclióforos se assemelha mais às formas larvares do que aos adultos. Apesar de possuírem um plano corporal sofisticado, com extensas áreas ciliadas e uma mioanatomia complexa, descobrimos que o macho de ambas as espécies Symbion é composto por apenas algumas dezenas de células. Baseando-nos nestas observações, inferimos que a complexidade dos metazoários não se relaciona com o tamanho corporal nem com o número de células de um organismo. Estudos sobre a ultra-estrutura da fêmea revelaram, entre outras estruturas, um putativo poro genital, extensões citoplasmáticas do oócito e glândulas posteriores. Morfologia e implicações funcionais destas estruturas são aqui discutidas. A anatomia do protonefrídeo da larva cordóide é descrita. A arquitectura deste órgão diverge daquela presente noutros representantes de Nephrozoa, particularmente ao nível da área de filtração da célula terminal. As nossas observações são discutidas em termos filogenéticos. A maturação sexual em ciclióforos é investigada. Os nossos resultados sugerem que a transição de reprodução assexual a sexual se relacione com a idade da forma séssil, a “feeding stage”. A presença da larva Prometeus assente no tronco desta também poderá influenciar o processo, embora mais estudos sejam desejáveis para o comprovar. Os nossos resultados são discutidos integrativa e comparativamente com o conhecimento prévio sobre Cycliophora. A cumulação deste conhecimento será essencial para a compreensão da evolução e filogenia deste enigmático filo.

Motor delays in MDMA (ecstasy) exposed infants persist to 2years

Background Recreational use of 3,4 methylenedioxymethamphetamine (ecstasy, MDMA) is increasing worldwide. Its use by pregnant women causes concern due to potentially harmful effects on the developing fetus. MDMA, an indirect monoaminergic agonist and reuptake inhibitor, affects the serotonin and dopamine systems. Preclinical studies of fetal exposure demonstrate effects on learning, motor behavior, and memory. In the first human studies, we found prenatal MDMA exposure related to poorer motor development in the first year of life. In the present study we assessed the effects of prenatal exposure to MDMA on the trajectory of child development through 2 years of age. We hypothesized that exposure would be associated with poorer mental and motor outcomes. Materials and Methods The DAISY (Drugs and Infancy Study, 2003–2008) employed a prospective longitudinal cohort design to assess recreational drug use during pregnancy and child outcomes in the United Kingdom. Examiners masked to drug exposures followed infants from birth to 4, 12, 18, and 24 months of age. MDMA, cocaine, alcohol, tobacco, cannabis, and other drugs were quantified through a standardized clinical interview. The Bayley Scales (III) of Mental (MDI) and Motor (PDI) Development and the Behavior Rating Scales (BRS) were primary outcome measures. Statistical analyses included a repeated measures mixed model approach controlling for multiple confounders. Results Participants were pregnant women volunteers, primarily white, of middle class socioeconomic status, average IQ, with some college education, in stable partner relationships. Of 96 women enrolled, children of 93 had at least one follow-up assessment and 81 (87%) had ≥ two assessments. Heavier MDMA exposure (M = 1.3 ± 1.4 tablets per week) predicted lower PDI (p < .002), and poorer BRS motor quality from 4 to 24 months of age, but did not affect MDI, orientation, or emotional regulation. Children with heavier exposure were twice as likely to demonstrate poorer motor quality as lighter and non-exposed children (O.R. = 2.2, 95%, CI = 1.02–4.70, p < .05). Discussion Infants whose mothers reported heavier MDMA use during pregnancy had motor delays from 4 months to two years of age that were not attributable to other drug or lifestyle factors. Women of child bearing age should be cautioned about the use of MDMA and MDMA-exposed infants should be screened for motor delays and possible intervention.

Effects of active pharmaceutical ingredients in mussel mytilus galloprovincialis

More than 3000 types of active pharmaceutical ingredients (APIs) are applied in Human and veterinary medicine practice. These compounds are considered an emergent class of environmental contaminants with the ability to cause damage and unexpected effects to aquatic organisms, namely in species of high commercial value. APIs are ubiquitous in the environment being frequently detected in influents and effluents of waste water treatment plants (WWTPs), surface waters and more distressingly in the public tap water in concentrations ranging from ng to μg.L-1. Considering these premises, the present thesis focused on APIs detection in the Arade river water, the impact of summer period in APIs’ concentration alterations applying the passive sampler device, POCIS (polar organic compound integrative sampler), as well as, the assessment of the effects caused by non-steroidal anti-inflammatory drugs (NSAID) ibuprofen (IBU) and diclofenac (DCF) and antidepressant selective serotonin reuptake inhibitor (SSRI) fluoxetine as single and mixture exposures along with a classical contaminant copper (Cu) on a non-target species, mussel Mytilus galloprovincialis. For this purpose, a multibiomarker approach was applied namely including biomarkers of oxidative stress (antioxidant enzymes activities of superoxide dismutase – SOD, catalase – CAT, glutathione reductase – GR and Phase II glutathione-S-transferase), damage - lipid peroxidation (LPO), neurotoxic effects (through the activity of acetylcholinesterase enzyme - AChE) and endocrine disruption (through vitellogenin-like proteins measurement applying the indirect method of alkali-labile phosphate - ALP) after exposure of mussel species’ to selected APIs at environmental relevant concentrations. The main results highlighted the occurrence of 19 APIs in the river Arade from several distinct therapeutic classes. Stimulant caffeine, antiasthmatic theophylline, NSAID ibuprofen and analgesic paracetamol presented the highest concentrations. Summer impact was inconclusive due to each API transient concentration in each month. The multibiomarker results revealed distinct responses towards each selected API (as single exposure or as mixtures) that were tissue and time dependent. Several multistressor interactions were proposed for each biomarker. The results also revealed APIs potential to induce oxidative stress, LPO, neurotoxicity and endocrine disruption even at extremely low concentrations on a species extremely vulnerable to APIs presence highlighting the urgency on the development of methodologies able to prevent its entrance in the aquatic environment.

Do princípio da boa fé nos contratos de seguro

O objetivo deste estudo foi analisar os seguintes tópicos: a possibilidade de interpretação literal do artigo 798 do Código Civil brasileiro, a aplicação das súmulas 61 e 105 do STF, o cabimento de indenização à família do suicida, os entendimentos da neurociência sobre possibilidades que podem interferir na ideação suicida, a visão e, finalmente, posicionamentos do Superior Tribunal de Justiça (STJ) e do Supremo Tribunal Federal do Brasil e quanto ao pagamento da indenização estabelecido no contrato de seguro de vida em caso de suicídio do contratante antes dos dois anos da assinatura do contrato. Buscou-se, também, comparar a doutrina e jurisprudência do Brasil e de Portugal. Na estrutura, iniciou-se por considerações sobre a interpretação jurídica e, em seguida, foram desenvolvidos os capítulos acerca de negócio jurídico, dos contratos, dos contratos de seguro de vida e da boa fé presente e necessária. Como o foco principal eram os contratos de seguro de vida e baseando-se na doutrina e na jurisprudência, de modo geral, mesmo a legislação dos dois países diferindo em pequenos aspectos, concluiu-se que: (1) o seguro é a cobertura de evento futuro e incerto que poderá gerar o dever de indenizar por parte do segurador; (2) a boa-fé - que é presumida - constitui elemento intrínseco do seguro, e é caracterizada pela lealdade nas informações prestadas pelo segurado ao garantidor do risco pactuado; (3) o legislador procurou evitar fraudes contra as seguradoras na hipótese de contratação de seguro de vida por pessoas que já tinham a idéia de suicídio quando firmaram o instrumento contratual; (4) uma coisa é a contratação causada pela premeditação ao suicídio, que pode excluir a indenização. Outra, diferente, é a premeditação para o próprio ato suicida;(5) é possível a interpretação entre os enunciados das Súmulas 105 do STF e 61 da Corte Superior na vigência do Código Civil de 2002; e (6) as regras relativas aos contratos de seguro devem ser interpretadas sempre com base nos princípios da boa fé e da lealdade contratual. Essa premissa é extremamente importante para a hipótese de indenização securitária decorrente de suicídio, pois dela extraise que a presunção de boa fé deverá também prevalecer sobre a exegese literal do art. 798 do Código Civil 2002. O período de 02 anos contido na norma não deve ser examinado isoladamente, mas em conformidade com as demais circunstâncias que envolveram sua elaboração, pois seu objetivo certamente não foi substituir a prova da premeditação do suicídio pelo mero transcurso de um lapso temporal. Há de se distinguir a premeditação que diz respeito ao ato do suicídio daquela que se refere ao ato de contratar o seguro com afinalidade única de favorecer o beneficiário que receberá o capital segurado. Somente a última hipótese permite a exclusão da cobertura contratada, pois configura a má-fé contratual. Em Portugal, salvo em raras exceções, apenas o critério temporal tem sido considerado. Continuando com o objetivo deste estudo, pretendeu-se refletir sobre as pesquisas neurocientíficas acerca do suicídio e, nelas, constam aspectos efetivamente que merecem ser considerados pela ciência jurídica. Suicídio é tema complexo e digno de reflexões por parte de profissionais de várias áreas de atuação. Suas causas ainda são motivo de curiosidade e de investigação. A idéia de uma associação entre disfunção serotoninérgica e suicídio é antiga e bastante consistente, surgindo ainda nos anos 1970 com as primeiras pesquisas. Defende-se que a boa fé necessária nos contratos de seguro, especialmente nos de seguro de vida, prevalece mesmo nos casos em que o contratante se esquece ou deixa de informar algum detalhe que, mais tarde, possa vir a comprometer o recebimento do prêmio por seus beneficiários. Há fortes evidências de que determinantes neurobiológicos, independentes das doenças psiquiátricas, implicam em comportamento suicida, estudados especialmente nos últimos 20 anos. Assim, noções básicas sobre a neurobiologia do suicídio podem finalmente produzir ferramentas clínicas para tratar comportamento suicida e evitar mortes, além de poder nortear seguradoras na análise de propostas de seguros de vida. Textos legais não têm sido elaborados com fundamento na sedimentação existente nos repositórios da psicopatologia forense, psiquiatria, psicanálise e sociologia sobre o suicídio, disponíveis há décadas e de forma reiteradamente confirmados. Na mesma linha, os textos deixaram de lado incontáveis pesquisas sobre o tema, notadamente a respeito de sua etiologia, causas primárias, efeitos, e correlação com outras ciências, como neurociência, psiquiatria e psicanálise. Não buscaram informações sobre o comportamento singular do suicida, nem reconheceram o estado sui generis de desequilíbrio mental em que o ato final foi praticado. Sabe-se que os transtornos psiquiátricos são fundamentais para o entendimento do comportamento suicida, mas também já está comprovada a realidade de problemas comuns, como distúrbios do sono, e sono insuficiente é um problema da sociedade moderna. Dentre os neurotransmissores, a serotonina é considerada como a maior candidata a um vínculo etiológico entre distúrbios do sono e suicídio, pois suas alterações promovem estados de vigília e de início do sono. Como somente 14% de pessoas que tentaram suicídio tiveram pensamentos suicidaprévios à tentativa de suicídio de forma potencialmente impulsiva ou reativa, a insônia foi o fator importante visualizado antes de tentativas de suicídio graves e letais em relação a planosespecíficos de suicídio. Nas pesquisas neurocientíficas revisadas, constatou-se que: (1) a frequência de pesadelos está diretamente associada a maior risco de suicídios na população em geral; (2) sono de má qualidade está associado a suicídios na maturidade e velhice na população em geral; (3) sono curto (menos de cinco horas) está associado a maiores probabilidades de ideação suicida e tentativa de suicídio; (4) pesadelos frequentes são preditores de tentativas de suicídio; e (5) a presença de qualquer problema de sono está associada com maior risco de suicídio na população em geral. A associação entre redução da resposta de hormônio de crescimento e comportamento suicida nos pacientes com depressão só é encontrada quando há simultaneamente uma alteração serotoninérgica. Geneticamente analisados, determinantes neurobiológicos são independentes de transtorno psiquiátrico com o qual estão associados, pois muitos suicídios ocorrem de maneira inesperada. Além disso, quando se considera a depressão como único fator, percebe-se que muitas pessoas depressivas nunca se tornam suicidas e muitos suicídios são cometidos por pessoas consideradas normais.Quanto à colesterolemia, na maior categoria de concentração de colesterol total no soro, o risco relativo ajustado de suicídio violento é mais do que o dobro em comparação com a categoria mais baixa. Nas avaliações eletroencefalográficas em adolescentes suicidas pode-se dizer existir uma hipótese de ativação reduzida esquerda posterior, que não está relacionada à depressão, mas ao comportamento agressivo ou suicida. Essas abordagens da Neurociência servem, portanto, para indicar que um contratante de seguro de vida, mesmo saudável, pode estar vivenciando problemas da vida contemporânea e, mesmo sem jamais ter tido qualquer pensamento ou ideação suicida, vir a cometer esse ato extremo por alterações independentes de sua vontade. Entende-se que, neste foco, a ciência jurídica deve refletir para fazer inserir de maneira obrigatória nos pré-requisitos da apólice, informações sobre exames molecu-lares e sobre algum eventual distúrbio do sono, já que existem achados evidenciados sobre alguns fenômenos não antes considerados. Como abordado neste estudo, já existe uma seguradora portuguesa que solicitam exames moleculares, mas nenhuma no Brasil. Assim, isto indica já ser um início de mudança.