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1.
Mol Nutr Food Res ; 63(19): e1900327, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31394019

RESUMO

SCOPE: Ferulic acid (FA), a natural phenolic phytochemical abundantly present in whole grains, herbs, and dried fruits, exhibits anti-inflammatory, antioxidant, and neuroprotective effects. In the present study, the antidepressant-like effects of FA in male ICR mice using tail suspension test (TST) are investigated and its molecular mechanisms are explored. METHODS AND RESULTS: Oral administration of FA at a dose of 5 mg kg-1 for 7 days significantly reduces immobility of mice compared to vehicle-administered control group. Microarray and real-time PCR analyses reveal that FA upregulates the expression of several genes associated with cell survival and proliferation, energy metabolism, and dopamine synthesis in mice limbic system of brain. Interestingly, it is found that FA, unlike antidepressant drug bupropion, strongly promotes energy metabolism. Additionally, FA increases catecholamine (dopamine and noradrenaline), brain-derived neurotrophic factor, and ATP levels, and decreases glycogen levels in the limbic system of the mice brain. CONCLUSION: The research provides the first evidence that FA enhances energy production, which can be the underlying mechanism of the antidepressant-like effects of FA observed in this study.


Assuntos
Antidepressivos/farmacologia , Ácidos Cumáricos/farmacologia , Depressão/tratamento farmacológico , Metabolismo Energético/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/análise , Proliferação de Células/efeitos dos fármacos , Depressão/etiologia , Depressão/metabolismo , Modelos Animais de Doenças , Dopamina/análise , Dopamina/biossíntese , Expressão Gênica/efeitos dos fármacos , Elevação dos Membros Posteriores , Sistema Límbico/química , Sistema Límbico/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais/genética
2.
J Clin Invest ; 123(12): 5334-41, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24231353

RESUMO

Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chronically self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted metabolic mapping, where DREADD indicates designer receptors exclusively activated by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect-related physiological and behavioral changes. Altogether, our translational study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability.


Assuntos
Tonsila do Cerebelo/metabolismo , Transtorno Depressivo Maior/metabolismo , Encefalinas/fisiologia , Dependência de Heroína/metabolismo , Precursores de Proteínas/fisiologia , Adulto , Tonsila do Cerebelo/química , Tonsila do Cerebelo/diagnóstico por imagem , Animais , Clozapina/análogos & derivados , Clozapina/farmacologia , Corticosterona/sangue , Transtorno Depressivo Maior/genética , Drogas Desenhadas/farmacocinética , Encefalinas/análise , Encefalinas/biossíntese , Encefalinas/deficiência , Encefalinas/genética , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/fisiologia , Dependência de Heroína/genética , Humanos , Hungria , Sistema Límbico/química , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/metabolismo , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Neurônios/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Precursores de Proteínas/análise , Precursores de Proteínas/biossíntese , Precursores de Proteínas/deficiência , Precursores de Proteínas/genética , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Compostos Radiofarmacêuticos , Ratos , Ratos Long-Evans , Proteínas Recombinantes de Fusão/metabolismo , Estados Unidos
3.
Histochem Cell Biol ; 139(2): 267-81, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23052836

RESUMO

While tryptophan hydroxylase-2 (Tph2) null mutant (Tph2(-/-)) mice are completely deficient in brain serotonin (5-HT) synthesis, the formation of serotonergic neurons and pathfinding of their projections are not impaired. However, 5-HT deficiency, during development and in the adult, might affect morphological and functional parameters of other neural systems. To assess the influence of 5-HT deficiency on γ-amino butyric acid (GABA) systems, we carried out measurements of GABA concentrations in limbic brain regions of adult male wildtype (wt), heterozygous (Tph2(+/-)) and Tph2(-/-) mice. In addition, unbiased stereological estimation of GABAergic interneuron numbers and density was performed in subregions of amygdala and hippocampus. Amygdala and prefrontal cortex displayed significantly increased and decreased GABA concentrations, respectively, exclusively in Tph2(+/-) mice while no changes were detected between Tph2(-/-) and wt mice. In contrast, in the hippocampus, increased GABA concentrations were found in Tph2(-/-) mice. While total cell density in the anterior basolateral amygdala did not differ between genotypes, the number and density of the GABAergic interneurons were significantly decreased in Tph2(-/-) mice, with the group of parvalbumin (PV)-immunoreactive (ir) interneurons contributing somewhat less to the decrease than that of non-PV-ir GABAergic interneurons. Major morphological changes were also absent in the dorsal hippocampus, and only a trend toward reduced density of PV-ir cells was observed in the CA3 region of Tph2(-/-) mice. Our findings are the first to document that life-long reduction or complete lack of brain 5-HT transmission causes differential changes of GABA systems in limbic regions which are key players in emotional learning and memory processes. The changes likely reflect a combination of developmental alterations and functional adaptations of emotion circuits to balance the lack of 5-HT, and may underlie altered emotional behavior in 5-HT-deficient mice. Taken together, our findings provide further insight into the mechanisms how life-long 5-HT deficiency impacts the pathogenesis of anxiety- and fear-related disorders.


Assuntos
Neurônios GABAérgicos/metabolismo , Sistema Límbico/citologia , Sistema Límbico/metabolismo , Serotonina/deficiência , Triptofano Hidroxilase/deficiência , Ácido gama-Aminobutírico/metabolismo , Animais , Neurônios GABAérgicos/química , Neurônios GABAérgicos/citologia , Sistema Límbico/química , Masculino , Camundongos , Camundongos Knockout , Ácido gama-Aminobutírico/análise
4.
J Chem Neuroanat ; 48-49: 1-13, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23137816

RESUMO

The amygdaloid nuclei form an important hub of structures associated with diverse aspects of cognition and emotional behavior. Homologous structures have been determined in tetrapods, but homology of amygdala-like regions in bony fishes is presently unclear. Based on connectivity patterns, genoarchitecture, chemical neuroanatomy, and functional studies, we suggest that the dorsomedial portion of the pallium of Actinopterygii is the homolog of the basolateral/lateral amygdala ("frontotemporal amygdaloid system"), while the supracommissural and postcommissural portions of the subpallium are homologous to the extended central amygdala (central amygdaloid nucleus and bed nucleus of the stria terminalis). Nonetheless, the differentiation between these nuclei is not as clear-cut as in mammals, and there is no clear evidence for the existence of an "olfactory" medial amygdala in Actinopterygii, suggesting that the parcellation of one or two amygdaloid nuclei into many subnuclei occurred with the appearance of a true vomeronasal system.


Assuntos
Tonsila do Cerebelo/fisiologia , Sistema Nervoso Autônomo/fisiologia , Peixes/fisiologia , Sistema Límbico/fisiologia , Tonsila do Cerebelo/anatomia & histologia , Tonsila do Cerebelo/química , Animais , Sistema Nervoso Autônomo/anatomia & histologia , Sistema Nervoso Autônomo/química , Comportamento Animal/fisiologia , Evolução Biológica , Peixes/genética , Sistema Límbico/anatomia & histologia , Sistema Límbico/química
5.
Eur J Neurosci ; 36(4): 2547-55, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22789020

RESUMO

Chronic stress induces presynaptic and postsynaptic modifications in the paraventricular nucleus of the hypothalamus that are consistent with enhanced excitatory hypothalamo-pituitary-adrenocortical (HPA) axis drive. The brain regions mediating these molecular modifications are not known. We hypothesized that chronic variable stress (CVS) tonically activates stress-excitatory regions that interact with the paraventricular nucleus of the hypothalamus, culminating in stress facilitation. In order to identify chronically activated brain regions, ΔFosB, a documented marker of tonic neuronal activation, was assessed in known stress regulatory limbic and brainstem sites. Four experimental groups were included: CVS, repeated restraint (RR) (control for HPA habituation), animals weight-matched (WM) to CVS animals (control for changes in circulating metabolic factors due to reduced weight gain), and non-handled controls. CVS, (but not RR or WM) induced adrenal hypertrophy, indicating that sustained HPA axis drive only occurred in the CVS group. CVS (but not RR or WM) selectively increased the number of FosB/ΔFosB nuclei in the nucleus of the solitary tract, posterior hypothalamic nucleus, and both the infralimbic and prelimbic divisions of the medial prefrontal cortex, indicating an involvement of these regions in chronic drive of the HPA axis. Increases in FosB/ΔFosB-immunoreactive cells were observed following both RR and CVS in the other regions (e.g. the dorsomedial hypothalamus), suggesting activation by both habituating and non-habituating stress conditions. The data suggest that unpredictable stress uniquely activates interconnected cortical, hypothalamic, and brainstem nuclei, potentially revealing the existence of a recruited circuitry mediating chronic drive of brain stress effector systems.


Assuntos
Tronco Encefálico/fisiopatologia , Sistema Límbico/fisiopatologia , Estresse Psicológico/fisiopatologia , Animais , Tronco Encefálico/química , Sistema Límbico/química , Masculino , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/fisiologia , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/patologia
6.
Neuropsychopharmacology ; 37(9): 2161-72, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22588352

RESUMO

Brainstem noradrenergic neurons innervate the mesocorticolimbic reward pathway both directly and indirectly, with norepinephrine facilitating dopamine (DA) neurotransmission via α1-adrenergic receptors (α1ARs). Although α1AR signaling in the prefrontal cortex (PFC) promotes mesolimbic transmission and drug-induced behaviors, the potential contribution of α1ARs in other parts of the pathway, such as the ventral tegmental area (VTA) and nucleus accumbens (NAc), has not been investigated before. We found that local blockade of α1ARs in the medial NAc shell, but not the VTA, attenuates cocaine- and morphine-induced locomotion. To determine the neuronal substrates that could mediate these effects, we analyzed the cellular, subcellular, and subsynaptic localization of α1ARs and characterized the chemical phenotypes of α1AR-containing elements within the mesocorticolimbic system using single and double immunocytochemical methods at the electron microscopic (EM) level. We found that α1ARs are found mainly extra-synaptically in axons and axon terminals in the NAc and are enriched in glutamatergic and dopaminergic elements. α1ARs are also abundant in glutamatergic terminals in the PFC, and in GABA-positive terminals in the VTA. In line with these observations, microdialysis experiments revealed that local blockade of α1ARs attenuated the increase in extracellular DA in the medial NAc shell following administration of cocaine. These data indicate that local α1ARs control DA transmission in the medial NAc shell and behavioral responses to drugs of abuse.


Assuntos
Dopamina/fisiologia , Sistema Límbico/fisiologia , Núcleo Accumbens/fisiologia , Terminações Pré-Sinápticas/fisiologia , Receptores Adrenérgicos alfa 1/fisiologia , Transmissão Sináptica/fisiologia , Animais , Cocaína/administração & dosagem , Infusões Intraventriculares , Sistema Límbico/química , Sistema Límbico/efeitos dos fármacos , Masculino , Morfina/administração & dosagem , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Núcleo Accumbens/química , Núcleo Accumbens/efeitos dos fármacos , Terminações Pré-Sinápticas/química , Terminações Pré-Sinápticas/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa 1/análise , Transmissão Sináptica/efeitos dos fármacos
7.
Neurobiol Aging ; 32(12): 2314-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20097445

RESUMO

We have established a novel transgenic rat line carrying human microtubule-associated protein Tau-40 with mutation P301L. hTau-40/P301L transgenic male and female rats were followed up to 2 years of age. The hTau-40/P301L rats expressed human tau mRNA and protein in the limbic cortex and associated white matter, hippocampus and spinal cord. With increasing age, the staining density for phosphorylated tau increased in all these areas. Neither silver stains nor Fluoro-Jade staining indicated the presence of dying neurons, or axonal degeneration, and there was no evidence of increased gliosis or inflammation. However, some neurons did display dendritic abnormalities, and immunoblots revealed the presence of sarcosyl insoluble tau. A large test battery revealed no behavioral abnormalities in these rats, except a mild hyperactivity in the elevated plus maze. In conclusion, this transgenic tau rat may be a useful model for 'pretangle' pathology, although in this study conditions were not sufficient to induce significant neuronal loss or behavioral deficits.


Assuntos
Química Encefálica/genética , Modelos Animais , Mutação/genética , Proteínas tau/química , Proteínas tau/genética , Animais , Feminino , Hipocampo/química , Hipocampo/metabolismo , Humanos , Sistema Límbico/química , Sistema Límbico/metabolismo , Masculino , Ratos , Ratos Transgênicos , Medula Espinal/química , Medula Espinal/metabolismo
8.
J Neurochem ; 115(6): 1595-607, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20969569

RESUMO

Noradrenaline exerts inhibitory effects on seizure susceptibility. Subtype selective agonists and antagonists were used to identify the anticonvulsant hippocampal adrenoreceptors. Intrahippocampal dialysis was used for administration of all compounds, including pilocarpine for limbic seizure induction, and as the neurotransmitter sampling tool. The noradrenaline reuptake inhibitor maprotiline mediated anticonvulsant effects, associated with dose-dependent increases in extracellular hippocampal noradrenaline, dopamine and GABA levels. At high concentrations, maprotiline produced proconvulsant effects associated with high levels of noradrenaline, dopamine and glutamate. Maprotiline's anticonvulsant effect was blocked by administration of either a selective α(2) - and ß(2) -antagonist. α(2) -Antagonist administration with maprotiline was associated with a further increase in noradrenaline and dopamine from maprotiline alone; whereas ß(2) -antagonist administered with maprotiline inhibited the dopamine increases produced by maprotiline. α(1A) -Antagonism blocked the GABA-ergic but not the anticonvulsive effect of maprotiline. These results were confirmed as combined but not separate α(2) - and ß(2) -adrenoreceptor stimulation, using selective agonists, inhibited limbic seizures. Interestingly, α(1A) -receptor stimulation and α(1D) -antagonism alone also inhibited seizures associated with respectively significant hippocampal GABA increases and glutamate decreases. The main findings of this study are that (i) increased hippocampal noradrenergic neurotransmission inhibits limbic seizures via combined α(2) - and ß(2) -receptor activation and (ii) α(1A) - and α(1D) -adrenoreceptors mediate opposite effects on hippocampal excitability.


Assuntos
Agonistas Adrenérgicos/farmacologia , Antagonistas Adrenérgicos/farmacologia , Hipocampo/metabolismo , Sistema Límbico/metabolismo , Receptores Adrenérgicos/metabolismo , Convulsões/metabolismo , Agonistas Adrenérgicos/uso terapêutico , Antagonistas Adrenérgicos/uso terapêutico , Animais , Hipocampo/química , Hipocampo/efeitos dos fármacos , Sistema Límbico/química , Sistema Límbico/efeitos dos fármacos , Masculino , Subunidades Proteicas/agonistas , Subunidades Proteicas/antagonistas & inibidores , Subunidades Proteicas/metabolismo , Ratos , Ratos Wistar , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Convulsões/tratamento farmacológico
9.
Hypertens Res ; 33(1): 67-75, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19876064

RESUMO

Hypertension is associated with cognitive decline in elderly persons. We studied asymptomatic hypertensive subjects using brain magnetic resonance (MR) spectroscopy to evaluate metabolite impairments before the appearance of symptoms in patients with different treatment outcomes. In all, 14 healthy controls and 37 asymptomatic hypertensive patients (17 controlled and 20 resistant) underwent brain structural MR and MR spectroscopy of the posterior paralimbic (PPL) area and left frontal white matter. Ischemic burden (IB), global cortical atrophy and microbleeds were analyzed with visual scales. Metabolite ratios involving N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (mI) were computed. Ultrasound measurements, including intima-media thickness, plaques and hemodynamic ratios, were obtained. Intergroup differences in IB, atrophy and metabolite ratios, and the atrophy and IB relationship were assessed with parametric and nonparametric statistical tests. In addition, the impacts of demographic, analytic and clinical factors, ischemia and atrophy, and ultrasound measurements on metabolite ratios were assessed. The significance level was set at P

Assuntos
Lobo Frontal/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Sistema Límbico/metabolismo , Idoso , Anti-Hipertensivos/uso terapêutico , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Atrofia , Encéfalo/patologia , Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/epidemiologia , Creatina/metabolismo , Interpretação Estatística de Dados , Feminino , Lobo Frontal/química , Humanos , Hipertensão/diagnóstico por imagem , Sistema Límbico/química , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Resultado do Tratamento , Ultrassonografia
10.
Prog Neuropsychopharmacol Biol Psychiatry ; 33(2): 251-61, 2009 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-19100810

RESUMO

Stress-related psychopathology is particularly prevalent in women, although the neurobiological reason(s) for this are unclear. Dopamine (DA) and serotonin (5-HT) systems however, are known to play important adaptive roles in stress and emotion regulation. The aims of the present study included examination of sex differences in stress-related behaviour and neuroendocrine function as well as post mortem neurochemistry, with the main hypothesis that corticolimbic DA and 5-HT systems would show greater functional activity in males than females. Long-Evans rats of both sexes were employed. Additional factors incorporated included differential postnatal experience (handled vs. nonhandled) and adult mild stress experience (acute vs. repeated (5) restraint). Regional neurochemistry measures were conducted separately for left and right hemispheres. Behaviourally, females showed more exploratory behaviour than males in the elevated plus maze and an openfield/holeboard apparatus. Females also exhibited significantly higher levels of adrenocorticotrophic hormone and corticosterone at all time points in response to restraint stress than males across treatment conditions, although both sexes showed similar habituation in stress-induced ACTH activation with repeated mild stress. Neurochemically, females had significantly higher levels of DA (in ventromedial prefrontal cortex (vmPFC), insular cortex and n. accumbens) and 5-HT (in vmPFC, amygdala, dorsal hippocampus and insula) than males. In contrast, males had higher levels of the DA metabolite DOPAC or DOPAC/DA ratios than females in all five regions and higher levels of the 5-HT metabolite 5-HIAA or 5-HIAA/5-HT ratios in vmPFC, amygdala and insula, suggesting greater neurotransmitter utilization in males. Moreover, handling treatment induced a significant male-specific upregulation of 5-HT metabolism in all regions except n. accumbens. Given the adaptive role of 5-HT and DAergic neurotransmission in stress and emotion regulation, the intrinsic sex differences we report in the functional status of these systems across conditions, may be highly relevant to the differential vulnerability to disorders of stress and emotion regulation.


Assuntos
Córtex Cerebral/fisiologia , Dopamina/fisiologia , Manobra Psicológica , Sistema Límbico/fisiologia , Serotonina/fisiologia , Hormônio Adrenocorticotrópico/metabolismo , Animais , Animais Recém-Nascidos , Ansiedade/psicologia , Córtex Cerebral/química , Córtex Cerebral/metabolismo , Cromatografia Líquida de Alta Pressão , Dopamina/metabolismo , Feminino , Hidrocortisona/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Sistema Hipotálamo-Hipofisário/química , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Límbico/química , Sistema Límbico/metabolismo , Masculino , Gravidez , Ratos , Ratos Long-Evans , Restrição Física , Serotonina/metabolismo , Caracteres Sexuais , Estresse Psicológico/metabolismo
11.
Neuron ; 57(5): 760-73, 2008 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-18341995

RESUMO

The mesocorticolimbic dopamine system is essential for cognitive and emotive brain functions and is thus an important target in major brain diseases like schizophrenia, drug addiction, and attention deficit hyperactivity disorder. However, the cellular basis for the diversity in behavioral functions and associated dopamine-release pattern within the mesocorticolimbic system has remained unclear. Here, we report the identification of a type of dopaminergic neuron within the mesocorticolimbic dopamine system with unconventional fast-firing properties and small DAT/TH mRNA expression ratios that selectively projects to prefrontal cortex and nucleus accumbens core and medial shell as well as to basolateral amygdala. In contrast, well-described conventional slow-firing dopamine midbrain neurons only project to the lateral shell of the nucleus accumbens and the dorsolateral striatum. Among this dual dopamine midbrain system defined in this study by converging anatomical, electrophysiological, and molecular properties, mesoprefrontal dopaminergic neurons are unique, as only they do not possess functional somatodendritic Girk2-coupled dopamine D2 autoreceptors.


Assuntos
Dopamina/fisiologia , Sistema Límbico/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Dopamina/análise , Sistema Límbico/química , Sistema Límbico/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/química , Neurônios/citologia , Fenótipo , Córtex Pré-Frontal/química , Córtex Pré-Frontal/citologia
12.
Brain Struct Funct ; 212(5): 387-401, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18183420

RESUMO

Cytoarchitectonic characterization of borders is necessary for stereological studies (e.g., total cell number estimation), in which particular cortical areas have to be defined. In this study, cytoarchitectonic characteristics are described and illustrated for the rat ventral or orbital frontal cortical areas, i.e., the lateral-, ventrolateral-, ventral- and medial-orbital areas; and for the lateral frontal cortical areas, i.e., the agranular insular and the dorsolateral orbital cortical area. Each cytoarchitectonic-defined boundary is corroborated by one or more of the immunocytochemical stainings for dopaminergic fibers, SMI-32 positive neurons, calbindin and parvalbumin positive neurons. Each immunocytochemical staining, however, shows a characteristic subset of the cytoarchitectonical borders. The dorsal agranular insular area (AId) and the dorsolateral orbital area (DLO) have been subdivided into a dorsal and a ventral part based upon differences between these parts in the Nissl and immunocytochemical stainings. The posterior part of VLO has a different structure and is, therefore, indicated as VLOp (VLO, posterior part).


Assuntos
Química Encefálica , Sistema Límbico/química , Sistema Límbico/citologia , Neurônios/química , Córtex Pré-Frontal/química , Córtex Pré-Frontal/citologia , Animais , Calbindinas , Dopamina/análise , Imuno-Histoquímica , Masculino , Proteínas de Neurofilamentos/análise , Corpos de Nissl/química , Parvalbuminas/análise , Ratos , Ratos Wistar , Proteína G de Ligação ao Cálcio S100/análise
13.
Fertil Steril ; 89(3): 685-92, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17543959

RESUMO

OBJECTIVE: To measure brain serotonin-1A (5HT1A) receptor binding potential (BP) in healthy and depressed postpartum women. DESIGN: 5HT1A receptor BP was measured with positron emission tomography by using [(11)C]WAY100635 a single time. Multivariate analysis of variance was used to determine depression effects on 5HT1A receptor BP in relevant brain regions. SETTING: An academic research environment. PATIENT(S): Seven postpartum healthy controls and nine postpartum depressed (PD) subjects with perinatal (antepartum or postpartum) depression onset. Of the nine PD subjects, five had unipolar depression, and four had bipolar disorder. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 5HT1A receptor BP. RESULT(S): Age, time since delivery, and reproductive hormones did not differ between groups. Postsynaptic 5HT1A receptor binding in postpartum depression was reduced 20%-28% relative to controls, with most significant reductions in anterior cingulate and mesiotemporal cortices. CONCLUSION(S): Postsynaptic 5HT1A receptor binding is reduced in PD women by a similar magnitude as has been shown in other depression samples. The postpartum hormonal milieu and the large proportion of bipolar spectrum subjects in the PD group may have accentuated this finding in this small sample. Recognition of this neurobiological deficit in postpartum depression may be useful in the development of treatments and prevention strategies for this disabling disorder.


Assuntos
Química Encefálica , Depressão Pós-Parto/diagnóstico por imagem , Sistema Límbico/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Receptor 5-HT1A de Serotonina/análise , Adulto , Aleitamento Materno , Radioisótopos de Carbono , Estudos de Casos e Controles , Depressão Pós-Parto/metabolismo , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Sistema Límbico/química , Hormônio Luteinizante/sangue , Piperazinas/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Progesterona/sangue , Prolactina/sangue , Ligação Proteica , Escalas de Graduação Psiquiátrica , Piridinas/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Antagonistas da Serotonina/metabolismo , Fatores de Tempo
14.
Neurology ; 69(4): 356-9, 2007 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-17646627

RESUMO

We used an autopsy series to determine whether the newest dementia with Lewy bodies (DLB) consensus pathologic classification correlates with premortem diagnosis of DLB. Neocortical sections from a total of 95 cases with Lewy bodies were stained with alpha-synuclein antibodies. We assigned cases according to the DLB consensus' categories and found a significant association with the premortem clinical diagnosis of DLB. Clinical diagnosis of DLB, however, depended on the presence of low Alzheimer disease pathology (by Braak staging) rather than on Lewy body distribution.


Assuntos
Encéfalo/patologia , Corpos de Lewy/patologia , Doença por Corpos de Lewy/classificação , Doença por Corpos de Lewy/patologia , Neurônios/patologia , Doença de Alzheimer/patologia , Tronco Encefálico/química , Tronco Encefálico/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Corpos de Lewy/química , Sistema Límbico/química , Sistema Límbico/patologia , Neocórtex/química , Neocórtex/patologia , Neurônios/química , Fenótipo , Valor Preditivo dos Testes , alfa-Sinucleína/análise
15.
Artigo em Russo | MEDLINE | ID: mdl-17025198

RESUMO

Relationship between the blood level of calcium and the level of catecholamines in the brain limbic structures was studied in passive avoidance conditioning and extinction in rats with hypoparathyreosis. After parathyroidectomy, conditioning processes were shown to be impaired as a result of a disorder of calcium supply. In hypoparathyreosis, not only the basic dopamine and noradrenalin levels change, but catecholamine dynamics in learning and forced extinction of a passive avoidance reaction shifts. The results point to the deranged functioning of dopamine and noradrenaline brain systems as a result of disorders in calcium homeostasis. These shifts result in disorders of conditioning and development of an adaptive behavioral strategy.


Assuntos
Cálcio/sangue , Catecolaminas/análise , Condicionamento Psicológico , Hipoparatireoidismo/fisiopatologia , Memória/fisiologia , Animais , Encéfalo/metabolismo , Dopamina/fisiologia , Sistema Límbico/química , Sistema Límbico/metabolismo , Norepinefrina/fisiologia , Ratos , Ratos Wistar
16.
Alcohol Clin Exp Res ; 30(4): 606-20, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16573578

RESUMO

BACKGROUND: To extend the known phenotype of strains commonly used in the development of mutant mice, ethanol, saccharin, and caffeine preferences were examined in C57Bl/6J, CD-1, and hybrid C57Bl/6J x CD-1 mice. As dopaminergic mechanisms are inherently involved in the neuronal processing of many drugs of abuse (including ethanol), and an important role for adenosine-dopamine interactions has also been reported, the dopaminergic and purinergic neurochemical profiles of mice were compared against the consummatory phenotype observed. METHODS: Ethanol (5% v/v), saccharin (0.1% w/v), and caffeine (0.1% w/v) consumption and preference were examined using a 2-bottle free-choice paradigm. Dopamine and adenosine receptor and transporter mRNA and protein density were quantified using in situ hybridization histochemistry and in vitro autoradiography, respectively. RESULTS: C57Bl/6J and hybrid C57Bl/6J x CD-1 mice demonstrated a clear ethanol preference, voluntarily consuming large quantities of ethanol when given the choice between drinking vessels containing either ethanol or water. Conversely, CD-1 mice were characterized as ethanol-avoiding under the present paradigm. Differences in D(1) receptor mRNA between the strains were consistent with the observed behavioral differences in ethanol preference. The high ethanol-preferring phenotype of C57Bl/6J mice could not be directly linked to alterations in dopamine transporter neurochemistry and/or enkephalin levels as proposed by earlier researchers. Ethanol-seeking behavior appeared to correlate with D2 receptor expression, however, with evidence that ethanol-preferring mice also exhibit an increased density of D2 receptors within limbic dopaminergic projection nuclei. Interestingly, strain differences in the expression of the ethanol-sensitive nucleoside transporter paralleled differences in ethanol consumption, a novel finding consonant with purinergic involvement in dopamine-related behaviors. CONCLUSIONS: This study has highlighted the relevance of alterations in dopamine receptor expression and purinergic modulation within the mesolimbic pathway and predisposition toward the development of ethanol-seeking behavior.


Assuntos
Adenosina/análise , Dopamina/análise , Etanol/administração & dosagem , Sistema Límbico/química , Animais , Núcleo Caudado/química , Feminino , Preferências Alimentares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Condutos Olfatórios/química , Putamen/química , RNA Mensageiro/análise , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Sacarina/administração & dosagem , Caracteres Sexuais , Especificidade da Espécie
17.
J Neurosci ; 25(8): 2102-7, 2005 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-15728850

RESUMO

Dyskinesia represents a debilitating complication of L-3,4-dihydroxyphenylalanine (L-dopa) therapy for Parkinson's disease. Such motor manifestations are attributed to pathological activity in the motor parts of basal ganglia. However, because consistent funneling of information takes place between the sensorimotor, limbic, and associative basal ganglia domains, we hypothesized that nonmotor domains play a role in these manifestations. Here we report the changes in 2-deoxyglucose (2-DG) accumulation in the sensorimotor, limbic, and associative domains of basal ganglia and thalamic nuclei of four groups of nonhuman primates: normal, parkinsonian, parkinsonian chronically treated with L-dopa without exhibiting dyskinesia, and parkinsonian chronically treated with L-dopa and exhibiting overt dyskinesia. Although nondyskinetic animals display a rather normalized metabolic activity, dyskinetic animals are distinguished by significant changes in 2-DG accumulation in limbic- and associative-related structures and not simply in sensorimotor-related ones, suggesting that dyskinesia is linked to a pathological processing of limbic and cognitive information. We propose that these metabolic changes reflect the underlying neural mechanisms of not simply motor dyskinesias but also affective, motivational, and cognitive disorders associated with long-term exposure to L-dopa.


Assuntos
Gânglios da Base/fisiopatologia , Discinesia Induzida por Medicamentos/fisiopatologia , Levodopa/toxicidade , Sistema Límbico/fisiopatologia , Animais , Gânglios da Base/química , Desoxiglucose/farmacocinética , Discinesia Induzida por Medicamentos/metabolismo , Feminino , Globo Pálido/química , Globo Pálido/fisiopatologia , Levodopa/uso terapêutico , Sistema Límbico/química , Macaca fascicularis , Córtex Motor/química , Córtex Motor/fisiopatologia , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/fisiopatologia , Núcleos Septais/química , Núcleos Septais/fisiopatologia , Córtex Somatossensorial/química , Córtex Somatossensorial/fisiopatologia , Substância Negra/química , Substância Negra/fisiopatologia , Núcleo Subtalâmico/química , Núcleo Subtalâmico/fisiopatologia
18.
Neuroendocrinology ; 82(5-6): 306-19, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16721035

RESUMO

Glucocorticoids and corticotropin-releasing hormone (CRH) are key regulators of stress responses. Different types of stress activate the CRH system; in hypothalamus, CRH expression and release are increased by physical or psychological stressors while in amygdala, preferentially by psychological stress. Learning and memory processes are modulated by glucocorticoids and stress at different levels. To characterize the kind of stress provoked by a hippocampal-dependent task such as spatial learning, we compared the expression profile of glucocorticoid receptor (GR), pro-CRH and CRH-R1 mRNAs (analyzed by RT-PCR), in amygdala, hippocampus and hypothalamus and quantified serum corticosterone levels by radioimmunoassay at different stages of training. mRNA levels of brain-derived neurotrophic factor (BDNF) were also quantified due to its prominent role in learning and memory processes. Male Wistar rats trained for 1, 3 or 5 days in the Morris water-maze (10 trials/day) were sacrificed 5-60 min the after last trial. A strong stress response occurred at day one in both yoked and trained animals (increased corticosterone and hypothalamic pro-CRH and CRH-R1 mRNA levels); changes gradually diminished as the test progressed. In amygdala, pro-CRH mRNA levels decreased while those of BDNF augmented when stress was highest, in yoked and trained animals. Hippocampi, of both yoked and trained groups, had decreased levels of GR mRNA on days 1 and 3, normalizing by day 5, while those of pro-CRH and CRH-R1 increased after the 3rd day. Increased gene expression, specifically due to spatial learning, occurred only for hippocampal BDNF since day 3. These results show that the Morris water-maze paradigm induces a strong stress response that is gradually attenuated. Inhibition of CRH expression in amygdala suggests that the stress inflicted is of physical but not of psychological nature and could lead to reduced fear or anxiety.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Hormônio Liberador da Corticotropina/genética , Sistema Límbico/química , Aprendizagem em Labirinto/fisiologia , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Glucocorticoides/genética , Estresse Fisiológico/fisiopatologia , Tonsila do Cerebelo/química , Tonsila do Cerebelo/fisiologia , Animais , Ansiedade/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/análise , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Corticosterona/sangue , Hormônio Liberador da Corticotropina/análise , Hormônio Liberador da Corticotropina/fisiologia , Regulação da Expressão Gênica/fisiologia , Hipocampo/química , Hipocampo/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Hipotálamo/química , Hipotálamo/fisiologia , Hibridização In Situ , Sistema Límbico/fisiologia , Masculino , Sistema Hipófise-Suprarrenal/fisiologia , RNA Mensageiro/análise , RNA Mensageiro/genética , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/análise , Receptores de Hormônio Liberador da Corticotropina/fisiologia , Receptores de Glucocorticoides/análise , Receptores de Glucocorticoides/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Comportamento Espacial/fisiologia , Estresse Fisiológico/etiologia , Fatores de Tempo , Água
19.
Ann N Y Acad Sci ; 1021: 33-50, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15251872

RESUMO

Impulsive choice, one aspect of impulsivity, is characterized by an abnormally high preference for small, immediate rewards over larger delayed rewards, and can be a feature of adolescence, but also attention-deficit/hyperactivity disorder (ADHD), addiction, and other neuropsychiatric disorders. Both the serotonin and dopamine neuromodulator systems are implicated in impulsivity; manipulations of these systems affect animal models of impulsive choice, though these effects may depend on the receptor subtype and whether or not the reward is signaled. These systems project to limbic cortical and striatal structures shown to be abnormal in animal models of ADHD. Damage to the nucleus accumbens core (AcbC) causes rats to exhibit impulsive choice. These rats are also hyperactive, but are unimpaired in tests of visuospatial attention; they may therefore represent an animal model of the hyperactive-impulsive subtype of ADHD. Lesions to the anterior cingulate or medial prefrontal cortex, two afferents to the AcbC, do not induce impulsive choice, but lesions of the basolateral amygdala do, while lesions to the orbitofrontal cortex have had opposite effects in different tasks measuring impulsive choice. In theory, impulsive choice may emerge as a result of abnormal processing of the magnitude of rewards, or as a result of a deficit in the effects of delayed reinforcement. Recent evidence suggests that AcbC-lesioned rats perceive reward magnitude normally, but exhibit a selective deficit in learning instrumental responses using delayed reinforcement, suggesting that the AcbC is a reinforcement learning system that mediates the effects of delayed rewards.


Assuntos
Sistema Límbico/fisiologia , Reforço Psicológico , Adolescente , Animais , Comportamento Animal , Química Encefálica/fisiologia , Comportamento de Escolha/fisiologia , Dopamina/metabolismo , Humanos , Comportamento Impulsivo/fisiopatologia , Sistema Límbico/anatomia & histologia , Sistema Límbico/química , Modelos Psicológicos , Neuroanatomia/métodos , Neuroquímica/métodos , Serotonina/metabolismo
20.
Rev Neurol ; 38(3): 284-91, 2004.
Artigo em Espanhol | MEDLINE | ID: mdl-14963860

RESUMO

The assessment of memory functions related to medial temporal lobe has become one of the most important issues on current neuropsychology. On this communication, we review the results which our research group has achieved using two functional magnetic resonance Image procedures to assess memory function: Hometown walking task and an encoding/retrieval task using complex images. Nine patients with tumoural temporal lesions performed the hometown walking task. The results of these patients showed either a bilateral or contralesional representation of memory function. These results confirm those obtained by Jokeit, Okujava y Woermann (2001), and they seem to prove that this protocol is useful to determine the preservation of memory function in the non damaged hemisphere. On the other hand, the images encoding/retrieval task has been run by two groups of four patients diagnosed as Alzheimer disease and mild cognitive impairment, and another group of five patients who participated as a control group. According to our hypothesis, the results have shown a lower activation at the left parahippocampal gyrus in mild cognitive impairment and Alzheimer disease patients than controls, just as a lower bilateral activation in the same structure for the Alzheimer group than the control group. As a whole, our results show how important may become functional magnetic resonance image for neuropsychological assessment of memory, and as a diagnostic tool for CNS diseases.


Assuntos
Doença de Alzheimer/patologia , Lobectomia Temporal Anterior , Epilepsia do Lobo Temporal/cirurgia , Sistema Límbico/patologia , Imageamento por Ressonância Magnética , Transtornos da Memória/patologia , Cuidados Pré-Operatórios , Lobo Temporal/patologia , Adulto , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Química Encefálica , Mapeamento Encefálico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/patologia , Feminino , Humanos , Transtornos da Linguagem/prevenção & controle , Sistema Límbico/química , Sistema Límbico/fisiopatologia , Espectroscopia de Ressonância Magnética , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/prevenção & controle , Pessoa de Meia-Idade , Testes Neuropsicológicos , Complicações Pós-Operatórias/prevenção & controle , Lobo Temporal/química , Lobo Temporal/fisiopatologia
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