Relación entre atrofia cortical difusa y desempeño cognitivo : estudio en población mayor de 60 años en un hospital universitario en la ciudad de Bogotá

El presente trabajo tuvo como objetivo evaluar la existencia de la relación entre la atrofia cortical difusa objetivada por neuroimagenes cerebrales y desempeños cognitivos determinados mediante la aplicación de pruebas neuropsicológicas que evalúan memoria de trabajo, razonamiento simbólico verbal y memoria anterógrada declarativa. Participaron 114 sujetos reclutados en el Hospital Universitario Mayor Méderi de la ciudad de Bogotá mediante muestreo de conveniencia. Los resultados arrojaron diferencias significativas entre los dos grupos (pacientes con diagnóstico de atrofia cortical difusa y pacientes con neuroimagenes interpretadas como dentro de los límites normales) en todas las pruebas neuropsicológicas aplicadas. Respecto a las variables demográficas se pudo observar que el grado de escolaridad contribuye como factor neuroprotector de un posible deterioro cognitivo. Tales hallazgos son importantes para determinar protocoles tempranos de detección de posible instalación de enfermedades neurodegenerativas primarias.

Imagem por ressonância magnética na investigação da cabeça de cães

A imagem por ressonância magnética (IRM) é o método de diagnóstico por imagem não invasivo mais sensível para avaliar as partes moles, particularmente o encéfalo, porém trata-se de uma técnica onerosa. O método fundamenta-se no fenômeno da ressonância magnética nuclear que ocorre quando núcleos atômicos com propriedades magnéticas presentes no corpo são submetidos a um campo magnético intenso, sendo posteriormente excitados por energia de radiofrequência e gerando, por sua vez, um sinal de onda de radiofrequência capaz de ser captado por uma antena receptora, passando por um processo matemático, chamado Transformada de Fourier, para posterior formação da imagem. Esse estudo objetivou realizar 10 exames completos da cabeça em cadáveres de cães normais à IRM e confeccionar um Atlas com as estruturas identificadas. As imagens foram adquiridas em um aparelho de ressonância magnética Gyroscan S15/HP Philips com campo magnético de 1,5Tesla. Os cadáveres foram posicionados com a cabeça no interior de uma bobina de cabeça humana e foram submetidos a cortes iniciais sagitais a partir de onde se planejou os cortes transversais e dorsais nas sequências de pulso spin-eco T1, T2 e DP. Em T1 utilizou-se TR=400ms e TE=30ms, T2 utilizou-se TR=2000ms e TE=80ms e na DP utilizou-se TR=2000ms e TE=30ms. A espessura do corte foi de 4mm, o número de médias foi igual a 2, a matriz foi de 256x256, o fator foi igual a 1,0 e o campo de visão foi de 14cm. A duração do exame completo da cabeça foi de 74,5minutos. As imagens obtidas com as sequências utilizadas e com a bobina de cabeça humana foram de boa qualidade. Em T1 a gordura tornou-se hiperintensa e o líquido hipointenso. Em T2 a gordura ficou menos hiperintensa e o líquido hiperintenso. A cortical óssea e o ar foram hipointensos em todas as sequências utilizadas devido a baixa densidade de prótons. A sequência DP mostrou o melhor contraste entre a substância branca e cinzenta quando comparada a T2 e a T1. T2 evidenciou o líquido cefalorraquidiano tornando possível a distinção dos sulcos e giros cerebrais. Através do exame de IRM foi possível, pelo contraste, identificar as estruturas ósseas componentes da arquitetura da região, músculos, grandes vasos venosos e arteriais e estruturas do sistema nervoso central, além de elementos do sistema digestório, respiratório e estruturas dos olhos entre outras. Nesse estudo as IRM adquiridas nas sequências T1, DP e T2 foram complementares para o estudo dos aspectos anatômicos da cabeça de cães demonstrando-os com riqueza de detalhes. O tempo requerido para o exame completo da cabeça é compátivel para uso em animais vivos desde que devidamente anestesiados e controlados. Os resultados obtidos por esse trabalho abrem caminho em nosso meio, para o estudo de animais vivos e para o início da investigação de doenças, principalmente as de origem neurológica, visto ser esta técnica excelente para a visibilização do encéfalo.

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood and adult-onset schizophrenia, bipolar disorder, attention-deficit/ hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages. (C) 2004 Published by Elsevier Inc.

Involvement of the midbrain tectum in the unconditioned fear promoted by morphine withdrawal

The midbrain rectum structures, dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), are involved in the organization of fear and anxiety states during the exposure to dangerous stimuli. Since opiate withdrawal is associated with increased anxiety in both humans and animals, this study aimed to investigate the possible sensitization of the neural substrates of fear in the midbrain tectum and its influence on the morphine withdrawal-induced anxiety. For the production of drug withdrawal, rats received morphine injections (10 mg/kg; s.c.) twice daily during 10 days. Forty-eight hours after the interruption of the chronic treatment, independent groups were probed in the elevated plus-maze and open-field tests. Additional groups of animals were implanted with a bipolar electrode into the dPAG OF the IC and submitted to the electrical stimulation of these structures for the determination of the freezing and escape thresholds after 48 h of withdrawal. Our results showed that the morphine withdrawal promoted clear-cut levels of anxiety without the somatic signs of opiate withdrawal. Moreover, morphine-withdrawn rats had an increase in the reactivity to the electrical stimulation of the dPAG and the IC. These findings suggest that the increased anxiety induced by morphine withdrawal is associated with the sensitization of the neural substrates of fear in the dPAG and the IC. So, the present results give support to the hypothesis that withdrawal from chronic treatment with morphine leads to fear states possibly engendered by activation of the dPAG and IC, regardless of the production of somatic symptoms. (C) 2008 Elsevier B.V. All rights reserved.

Glial cell line-derived neurotrophic factor added to a sciatic nerve fragment grafted in a spinal cord gap ameliorates motor impairments in rats and increases local axonal growth

Purpose: The aversive nature of regenerative milieu is the main problem related to the failure of neuronal restoration in the injured spinal cord which however might be addressed with an adequate repair intervention. We evaluated whether glial cell line-derived neurotrophic factor (GDNF) may increase the ability of sciatic nerve graft, placed in a gap promoted by complete transections of the spinal cord, to enhance motor recovery and local fiber growth. Methods: Rats received a 4 mm-long gap at low thoracic level and were repaired with a fragment of the sciatic nerve. GDNF was added (NERVE+GDNF) or not to the grafts (NERVE-GDNF). Motor behavior score (BBB) and sensorimotor tests-linked to the combined behavior score (CBS), which indicate the degree of the motor improvement and the percentage of functional deficit, respectively, and also the spontaneous motor behavior in an open field by means of an infrared motion sensor activity monitor were analyzed. At the end of the third month post surgery, the tissue composed by the graft and the adjacent regions of the spinal cord was removed and submitted to the immunohistochemistry of the neurofilament-200 (NF-200), growth associated protein-43 (GAP-43), microtubule associated protein-2 (MAP-2), 5-hidroxytryptamine (serotonin, 5-HT) and calcitonin gene related peptide (CGRP). The immunoreactive fibers were quantified at the epicenter of the graft by means of stereological procedures. Results: Higher BBB and lower CBS levels (p < 0.001) were found in NERVE+GDNF rats. GDNF added to the graft increased the levels of individual sensorimotor tests mainly at the third month. Analysis of the spontaneous motor behavior showed decreases in the time and number of small movement events by the third month without changes in time and number of large movement events in the NERVE+GDNF rats. Immunoreactive fibers were encountered inside the grafts and higher amounts of NF-200, GAP-43 and MAP-2 fibers were found in the epicenter of the graft when GDNF was added. A small amount of descending 5-HT fibers was seen reentering in the adjacent caudal levels of the spinal cords which were grafted in the presence of GDNF, event that has not occurred without the neurotrophic factor. GDNF in the graft also led to a large amount of MAP-2 perikarya and fibers in the caudal levels of the cord gray matter, as determined by the microdensitometric image analysis. Conclusions: GDNF added to the nerve graft favored the motor recovery, local neuronal fiber growth and neuroplasticity in the adjacent spinal cord.

Lower N-Acetyl-Aspartate Levels in Prefrontal Cortices in Pediatric Bipolar Disorder: A (1)H Magnetic Resonance Spectroscopy Study

Objective: The few studies applying single-voxel(1)H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low N-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol / phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study was to evaluate NAA, glycerophosphocholine plus phosphocholine (GPC+PC) and PCr+Cr in various frontal cortical areas in children and adolescents with BD. We hypothesized that NAA levels within the prefrontal cortex are lower in BD patients than in healthy controls, indicating neurodevelopmental alterations in the former. Method: We studied 43 pediatric patients with DSM-IV BD (19 female, mean age 13.2 +/- 2.9 years) and 38 healthy controls (79 female, mean age 13.9 +/- 2.7 years). We conducted multivoxel in vivo (1)H spectroscopy measurements at 1.5 Tesla using a long echo time of 272 ms to obtain bilateral metabolite levels from the medial prefrontal cortex (MPFC), DLPFC (white and gray matter), cingulate (anterior and posterior), and occipital lobes. We used the nonparametric Mann-Whitney U test to compare neurochemical levels between groups. Results: In pediatric BD patients, NAA and GPC+PC levels in the bilateral MPFC, and PCr+Cr levels in the left MPFC were lower than those seen in the controls. In the left DLPFC white matter, levels of NAA and PCr+Cr were also lower in BD patients than in controls. Conclusions: Lower NAA and PCr+Cr levels in the PFC of children and adolescents with BD may be indicative of abnormal dendritic arborization and neuropil, suggesting neurodevelopmental abnormalities. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(1):85-94.

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder ( BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray ( GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P = 0.01, right P = 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P = 0.01) and healthy groups (left P = 0.03, right P = 0.03). The Val/Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (P<0.01). There was a significant main effect of diagnosis on memory function (P = 0.04), but no interaction between diagnosis and genotype was found (P = 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD. Neuropsychopharmacology (2009) 34, 1904-1913; doi: 10.1038/npp.2009.23; published online 18 March 2009

Serotonergic neurotransmission in the dorsal raphe nucleus recruits in situ 5-HT2A/2C receptors to modulate the post-ictal antinociception

The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and humans. The aim of this study was to assess the involvement of the dorsal raphe nucleus (DRN) in the post-ictal antinociception. The second aim was to study the role of serotonergic intrinsic mechanisms of the DRN in this hypo-algesic phenomenon. Pentylenetetrazole (PTZ), an ionophore GABA-mediated Cl- influx antagonist, was peripherally used to induce tonic-clonic seizures in Wistar rats. The nociceptive threshold was measured by the tail-flick test. Neurochemical lesions of the DRN, performed with microinjection of ibotenic acid (1.0 mu g/0.2 mu L), caused a significant decrease of tonic-clonic seizure-induced antinociception, suggesting the involvement of this nucleus in this antinociceptive Process. Microinjections of methysergide (1.0 and 5.0 mu g/0.2 mu L), a non-selective serotonergic receptor antagonist, into DRN caused a significant decrease in the post-ictal antinociception in seizing animals, compared to controls, in all post-ictal periods Presently studied. These findings were corroborated by microinjections of ketanserin (at 1.0 and 5.0 mu g/0.2 mu L) into DRN. Ketanserin is an antagonist with large affinity for 5-HT2A/2C serotonergic receptors, which, in this Case, Caused a significant decrease in the tail-flick latencies in seizing animals, compared to controls after the first 20 min following tonic-clonic convulsive reactions. These results indicate that serotonergic neurotransmission of the DRN neuronal clusters is involved in the organization of the post-ictal hypo-algesia. The 5-HT2A/2C receptors of DRN neurons seem to be critically involved in the increase of nociceptive thresholds following tonic-clonic seizures. (c) 2008 Elsevier Inc, All rights reserved.

Role of homocysteic acid in the guinea pig (Cavia porcellus) anterior cingulate cortex in tonic immobility and the influence of NMDA receptors on the dorsal PAG

Tonic immobility (TI) is an innate defensive behaviour elicited by physical restriction and Postural inversion, and is characterised by a profound and temporary state of akinesis. Our previous studies demonstrated that glutamatergic stimulation of the dorsomedial/dorsolateral Portion of periaqueductal gray matter (dPAG) decreases the duration of TI in guinea pigs (Cavia porcellus). Furthermore, evidence suggests that the anterior cingulate cortex (ACC) constitutes an important Source of glutamate for the dPAG. Hence, in the current study, we investigated the effects of microinjection of the excitatory amino acid (EAA) agonist DL-homocysteic acid (DLH) and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 into the ACC on the duration of TI in guinea pigs. We also assessed the effect of the NMDA receptor antagonist (MK-801) into the dorsal periaqueductal gray matter (dPAG) prior to DLH microinjection into the ACC on the TI duration in the guinea pig. Our results demonstrated that DLH microinjections into the ACC decreased the duration of TI. This effect was blocked by previous MK-801 microinjections into the ACC or into the dPAG. The MK-801 microinjections alone did not influence TI duration. These results provide the new insight that EAAs in the ACC can decrease the duration of TI. The mechanism seems to be dependent on the NMDA receptors present in the ACC and in the dPAG. (C) 2009 Elsevier B.V. All rights reserved.

Role of dorsal raphe nucleus 5-HT(1A) and 5-HT(2) receptors in tonic immobility modulation in guinea pigs

Tonic immobility (TI) is an innate defensive behavior characterized by a state of physical inactivity and diminished responsiveness to environmental stimuli. Behavioral adaptations to changes in the external and internal milieu involve complex neuronal network activity and a large number of chemical neurotransmitters. The TI response is thought to be influenced by serotonin (5-HT) activity in the central nervous system (CNS) of vertebrates, but the neuronal groups involved in the mechanisms underlying this behavior are poorly understood. Owing to its extensive afferents and efferents, the dorsal raphe nucleus (DRN) has been implicated in a great variety of physiological and behavioral functions. in the current study, we investigated the influence of serotonergic 5-HT(1A) and 5-HT(2) receptor activity within the DRN on the modulation of TI behavior in the guinea pig. Microinjection of a 5-HT(1A) receptor agonist (8-OH-DPAT, 0.01 and 0.1 mu g) decreased TI behavior, an effect blocked by pretreatment with WAY-100635 (0.033 mu g), a 5-HT(1A) antagonist. In contrast, activation of 5-HT(2) receptors within the DRN (alpha-methyl-5-HT, 0.5 mu g) increased the TI duration, and this effect could be reversed by pretreatment with an ineffective dose (0.01 mu g) of ketanserine. Since the 5-HT(1A) and 5-HT(2) agonists decreased and increased, respectively, the duration of TI, different serotonin receptor subtypes may play distinct roles in the modulation of TI in the guinea pig. (C) 2009 Elsevier B.V. All rights reserved.

Modulation of tonic immobility in guinea pig PAG by homocysteic acid, a glutamate agonist

Tonic immobility (TI) is an innate defensive behavior elicited by physical restriction and postural inversion, and is characterized by a profound and temporary state of motor inhibition. The participation of the periaqueductal gray matter (PAG) in TI modulation has previously been described. In addition, the excitatory amino acids (EAA) are important mediators involved in the adjustment of several defensive responses produced by PAG. In the present study, we investigated the effect of microinjection of the EAA agonist DL-homocysteic acid (DLH) and the N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801) into the ventrolateral and dorsal PAG over the duration of TI in guinea pigs. Microinjection of 15 nmol/0.2 mu l of DLH into the ventrolateral PAG (vlPAG) and 30 nmol/0.2 mu l of DLH into the dorsal PAG (dPAG) promoted an increase and decrease in TI duration, respectively. These responses were blocked by prior microinjection of the NMDA receptor antagonist, MK-801 (3.6 nmol/0.2 mu l) at the same site. Microinjection of MK-801 alone into the APAG and dPAG did not alter the duration of TI episodes. These results suggest that NMDA receptors are involved in the modulation of TI in both the vlPAG and dPAG. In addition, PAC excitatory amino acids modulate the TI response via columnar organization of the PAC. In this manner, the vlPAG facilitates TI modulation whereas dPAG has an inhibitory role in TI. (C) 2008 Elsevier Inc. All rights reserved.

Development and reorganization of corticospinal projections in EphA4 deficient mice

The Eph family of receptor tyrosine kinases and their ligands, the ephrins, are important regulators of axon guidance and cell migration in the developing nervous system. Inactivation of the EphA4 gene results in axon guidance defects of the corticospinal tract, a major descending motor pathway that originates in the cortex and terminates at all levels of the spinal cord. In this investigation, we report that although the initial development of the corticospinal projection is normal through the cortex, internal capsule, cerebral peduncle, and medulla in the brain of EphA4 deficient animals, corticospinal axons exhibit gross abnormalities when they enter the gray matter of the spinal cord. Notably, many corticospinal axons fail to remain confined to one side of the spinal cord during development and instead, aberrantly project across the midline, terminating ipsilateral to their cells of origin. Given the possible repulsive interactions between EphA4 and one of its ligands, ephrinB3, this defect could be consistent with a loss of responsiveness by corticospinal axons to ephrinB3 that is expressed at the spinal cord midline. Furthermore, we show that EphA4 deficient animals exhibit ventral displacement of the mature corticospinal termination pattern, suggesting that developing corticospinal axons, which may also express ephrinB3, fail to be repelled from areas of high EphA4 expression in the intermediate zone of the normal spinal cord. Taken together, these results suggest that the dual expression of EphA4 on corticospinal axons and also within the surrounding gray matter is very important for the correct development and termination of the corticospinal projection within the spinal cord. J. Comp. Neurol. 436: 248-262, 2001. (C) 2001 Wiley-Liss, Inc.

The distribution and morphological characteristics of serotonergic cells in the brain of monotremes

The distribution and cellular morphology of serotonergic neurons in the brain of two species of monotremes are described. Three clusters of serotonergic neurons were found: a hypothalamic cluster, a cluster in the rostral brainstem and a cluster in the caudal brainstem. Those in the hypothalamus consisted of two groups, the periventricular hypothalamic organ and the infundibular recess, that were intimately associated with the ependymal wall of the third ventricle. Within the rostral brainstem cluster, three distinct divisions were found: the dorsal raphe nucleus (with four subdivisions), the median raphe nucleus and the cells of the supralemniscal region. The dorsal raphe was within and adjacent to the periaqueductal gray matter, the median raphe was associated with the midline ventral to the dorsal raphe, and the cells of the supralemniscal region were in the tegmentum lateral to the median raphe and ventral to the dorsal raphe. The caudal cluster consisted of three divisions: the raphe obscurus nucleus, the raphe pallidus nucleus and the raphe magnus nucleus. The raphe obscurus nucleus was associated with the dorsal midline at the caudal-most part of the medulla oblongata. The raphe pallidus nucleus was found at the ventral midline of the medulla around the inferior olive. Raphe magnus was associated with the midline of the medulla and was found rostral to both the raphe obscurus and raphe pallidus. The results of our study are compared in an evolutionary context with those reported for other mammals and reptiles. Copyright (C) 2002 S. Karger AG, Basel.

Efeitos do isolamento social neonatal, da fluoxetina e do lactato desódio sobre o pânico experimental induzido por cianeto de potássio ou estimulação da matéria cinzenta periaquedutal em ratos

Os ataques de pânico (AP) podem ser precipitados pela inalação de dióxido de carbono (CO2 5%) ou pela infusão de lactato de sódio 0,5 mol/L (LAC) em pacientes predispostos, mas não nos indivíduos sadios ou pacientes com outros transtornos psiquiátricos. Estas e outras observações sugeriram que os AP sejam "alarmes falsos de sufocamento". O TP também caracteriza-se pela alta comorbidade com ansiedade de separação da infância (ASI). De fato, a ASI tem sido considerada como um fator predisponente tanto do pânico como da resistência aos panicolíticos. Estudos pré-clínicos do nosso laboratório mostraram, por outro lado, que a fluoxetina (FLX) atenua o pânico experimental à estimulação elétrica da matéria cinzenta periaquedutal dorsal (MCPAd) e à injeção de cianeto de potássio (KCN) em doses e regimes similares aos empregados na clínica. Adicionalmente, estes estudos mostraram que o isolamento social neonatal (ISN), um modelo de ASI, abole os efeitos panicolíticos da fluoxetina (1-2 mg.kg-1.dia-1, 21 dias) no modelo de pânico por estimulação da MCPAd. Portanto, o presente trabalho avaliou os efeitos da administração de 4 mg/kg de FLX (Estudo-1) e da infusão de uma solução 0,5 mol/L de LAC (Estudo-2) sobre as respostas de pânico à estimulação da MCPAd ou à injeção de KCN, respectivamente, em ratos submetidos ao isolamento social neonatal tanto efetivo (ISN) quanto fictício (ISF). No Estudo-1, ratos Wistar machos adultos submetidos ao ISN (3 h diárias) ou ao ISF (somente manipulação), ao longo da lactação, foram implantados com eletrodos na MCPAd e tratados com salina (0,9%, SAL) ou FLX (4 mg.kg-1.dia-1) ao longo de 21 dias. Nos ratos tratados com SAL, enquanto os limiares das respostas de pânico mantiveram-se praticamente inalterados no grupo ISF, eles foram progressivamente aumentados no grupo ISN. Os ratos tratados com FLX4 apresentaram limiares mais elevados que aqueles dos ratos tratados com SAL. A comparação aos limiares basais mostrou que a FLX4 teve efeitos diferenciados nos grupos ISF e ISN, aumentando ou reduzindo seus limiares, respectivamente. Embora não tenhamos observado diferenças dos efeitos da FLX4 sobre os limiares de pânico dos grupos ISN e ISF, as variações percentuais em relação à sessão de triagem indicam que a FLX4 teve efeitos até mesmo facilitadores. Estes resultados estendem observações anteriores da ausência de efeitos de doses menores de FLX nos ratos submetidos ao ISN. Por sua vez, o Estudo-2 mostrou que a infusão endovenosa de uma concentração clinicamente eficaz de LAC (0,5 mol/L) não tem efeito algum sobre o pânico induzido pelo KCN em ratos tanto virgens quanto submetidos ao ISF ou ISN. Embora os últimos resultados sugiram que os AP ao KCN (em ratos) e LAC (em humanos) envolvam mecanismos distintos, a conclusão definitiva requer experimentos adicionais com concentrações maiores de LAC.

Efeito da privação de sono paradoxal e do bloqueio da síntese da corticosterona sobre os limiares da reação de defesa induzida pela estimulação elétrica da matéria cinzenta periaquedutal e colículo superior

O Transtorno do pânico (TP) é um transtorno mental comum que afeta até 5% da população em algum momento da vida, sendo caracterizada pela presença de ataques de pânico (AP) recorrentes. Constitui uma psicopatologia que pode ser afetada pela privação do sono (PS), relação que ainda é pouco compreendida. Neste contexto, modelos experimentais de AP e de PS são ferramentas úteis na investigação dessa possível correlação, especialmente motivado pela crescente condição de privação de sono, que tem se tornado cada vez mais frequente na sociedade moderna. Assim, este estudo avaliou os efeitos da privação de sono paradoxal (PSP) sobre os limiares dos comportamentos defensivos induzidos por estimulação intracraniana (EI) da MCPD e CS de ratos num modelo experimental de AP, assim como verificou a influência da corticosterona sobre esses limiares. Foram utilizados 160 ratos Wistar machos (300g), organizados em 4 grupos com 40 animais cada, como se segue: Grupo Controle (CTR) submetido à EI, porém sem PSP; Grupo Privação (PRV), submetido à EI e privado por 96 horas; Grupo Privação + Bloqueio da corticosterona (PRB), submetido ao tratamento com metirapona, EI, e privado por 96 horas, e Grupo Controle + Bloqueio da corticosterona (CTB), submetido ao tratamento com metirapona e EI, porém sem privação de sono. Após 10 dias do implante cirúrgico intracraniano de eletrodo na MCPD e CS, os animais passaram por 5 sessões de estimulação, como se segue: 1ª (TRI) considerada triagem - imediatamente antes da privação, 2ª (P48) após 48h de privação, 3ª (P96) após 96h de privação, 4ª (R48) após 48h de retirada da privação e 5ª (R96) após 96h de retirada da privação. As curvas de limiares das respostas individuais de defesa obtidas nas várias sessões de estimulação da MCPD e CS (TRI, P48, P96, R48 e R96) dos ratos foram comparadas entre si, bem como as curvas de limiares de uma dada resposta nos diferentes grupos (CTR, PRV, CTB e PRB). Além disso, os níveis de corticosterona (CORT) foram dosados nas diferentes sessões de EI, e comparadas num mesmo grupo, bem como nos diferentes grupos. No grupo CTR, todos os comportamentos foram iguais em todas as sessões quando comparados à TRI, entretanto, nos animais privados (PRV), o limiar do galope (GLP) reduziu significativamente em R48 e R96, não ocorrendo xix alterações nos demais comportamentos. Em contraste, no grupo PRB, o Trote (TRT) aumentou a partir de P48, enquanto o GLP não foi alterado em nenhuma sessão de EI. Na comparação entre os grupos, em Salto (SLT), Micção (MIC), Exoftalmia (EXO), Imobilidade (IMO), Defecação (DEF), TRT e GLP, não sofreram alterações decorrentes da CORT produzida decorrente da PSP, sugerindo que a corticosterona não altera os comportamentos defensivos característicos do Ataque de Pânico. Em adição, tais resultados sugerem que os efeitos tardios da PSP sobre os limiares de GLP possivelmente se devam a mecanismos neuroquímicos tempo-dependente.