RESUMO
Schizophrenia (SCZ) is a severe and chronic neurodevelopmental disorder with onset occurring during adolescence or early adulthood; notwithstanding, the brain dysfunction occurs before the disease and is not clinically evident. Recently, memantine (MEM) had been postulated as an effective preventive treatment in rats. In this study, was performed the Early Maternal Deprivation (EMD) protocol in Sprague-Dawley rats, establishing four groups (control, EMD, EMD treated with MEM, and MEM treatment). Behavioral parameters such as active linking (AL) and T maze were evaluated as well as quantitative brain histological changes at 3, 7, and 10 weeks of age, to understand the longitudinal demeanor of the disease. Prefrontal evoked potentials (PFEPs) were recorded to study functional synaptic connectivity and neuronal synchronicity changes. The results showed that EMD induces a decrease of AL and poor performance of T maze, in addition to volumetric changes of cortical and subcortical brain structures and abnormalities in PFEPs. The majority of this changes were absent by neonatal MEM administration. Taking into account that all these abnormalities are associated to SCZ, we propose to MEM as a potential preventive treatment.
Assuntos
Córtex Auditivo , Comportamento Animal , Disfunção Cognitiva/prevenção & controle , Corpo Estriado , Potenciais Evocados/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo , Privação Materna , Memantina/farmacologia , Córtex Pré-Frontal , Esquizofrenia/prevenção & controle , Animais , Animais Recém-Nascidos , Córtex Auditivo/efeitos dos fármacos , Córtex Auditivo/patologia , Córtex Auditivo/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Disfunção Cognitiva/etiologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Corpo Estriado/fisiopatologia , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memantina/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Gravidez , Ratos , Ratos Sprague-Dawley , Esquizofrenia/patologia , Esquizofrenia/fisiopatologiaRESUMO
Schizophrenia is considered a neurodevelopmental disorder; however, all the available treatment options are used when the disease becomes clinically significant in adolescence or early adulthood. Using a developmental rat model of schizophrenia, we examined whether neonatal treatment with memantine, an NMDA receptor modulator, can improve schizophrenic-like symptoms in adulthood. Early maternal deprivation in rats produces deficits in social interaction behaviors in adulthood. In contrast, memantine administrated in neonatal rats subjected to early maternal deprivation significantly reduces deficits in social interaction behaviors in adulthood. These results raise the possibility that pharmacological treatment with memantine at the early developmental stage helps people with a risk to develop schizophrenic-like symptoms.
RESUMO
OBJECTIVE: Research of electroencephalograph (EEG) power spectrum and mean frequency has shown inconsistent results in patients with schizophrenic, schizoaffective and bipolar disorders during medication when compared to normal subjects thus; the characterization of these parameters is an important task. METHODS: We applied quantitative EEG (qEEG) to investigate 38 control, 15 schizophrenic, 7 schizoaffective and 11 bipolar disorder subjects which remaine under the administration of psychotropic drugs (except control group). Absolute spectral power (ASP), mean frequency and hemispheric electrical asymmetry were measured by 19 derivation qEEG. Group mean values were compared with non parametrical Mann-Whitney test and spectral EEG maps with z-score method at p < 0.05. RESULTS: Most frequent drug treatments for schizophrenic patients were neuroleptic+antiepileptic (40% of cases) or 2 neuroleptics (33.3%). Schizoaffective patients received neuroleptic+benzodiazepine (71.4%) and for bipolar disorder patients neuroleptic+antiepileptic (81.8%). Schizophrenic (at all derivations except for Fp1, Fp2, F8 and T6) and schizoaffective (only at C3) show higher values of ASP (+57.7% and +86.1% respectively) compared to control group. ASP of bipolar disorder patients did not show differences against control group. The mean frequency was higher at Fp1 (+14.2%) and Fp2 (+17.4%) in bipolar disorder patients than control group, but no differences were found in frequencies between schizophrenic or schizoaffective patients against the control group. Majority of spectral differences were found at the left hemisphere in schizophrenic and schizoaffective but not in bipolar disorder subjects. CONCLUSION: The present report contributes to characterize quantitatively the qEEG in drug treated schizophrenic, schizoaffective or bipolar disorder patients.
RESUMO
The objective of this study was to determine the effect of memantine on schizophrenia-like symptoms in a ketamine-induced social withdrawal model in rats. We examined therapeutic effects of memantine, an NMDA antagonist, and haloperidol, a classic antipsychotic drug, on this behavioral model. Administration of memantine (10 or 15 mg·kg(-1)) significantly reduced ketamine-induced social withdrawal, and this effect was more effective than that of haloperidol (0.25 mg·kg(-1)) by restoring the social interaction between rats with no modification in general motor activity. These results suggest that memantine could have a therapeutic potential for schizophrenia.
RESUMO
Bipolar disorder, like the majority of psychiatric disorders, is considered a neurodevelopment disease of neurodevelopment. There is an increased rate of neuronal birth and death during this development period. In the particular case of the processes that determine neuronal death, it is known that those neurons that establish connections have to be removed from the central nervous system. There is a deficit of GABAergic interneurons in the cerebral cortex in bipolar disorder, accompanied by overexpression of proapoptic genes. There is also an alteration in the expression of molecules that mediate in the migration of these neurons and their inclusion in functional synapsis during the foetal stage. The role of these molecules in the neuronal death pathways by apoptosis will be reviewed here in an attempt to establish biological hypotheses of the genesis of bipolar disorder.