RESUMO
Reports from recent years provide compelling evidence about the structure and the existence of functional topography in the cerebellum. However, most of them focused on the motor functions of the cerebellum. Recent studies suggest the involvement of the posterior lobe of the cerebellum in the context of neurodegenerative and cognitive disorders. The pathophysiology of these diseases is not sufficiently understood, and recent studies indicate that it could also affect additional subregions of the cerebellum. Anatomical and clinical studies, combined with neuroimaging, provide new ways of thinking about the organization and functioning of the cerebellum. This review summarizes knowledge about the topography and functions of the cerebellum, and focuses on its anatomical and functional contributions to the development of neurological diseases.
RESUMO
In humans, pyruvate dehydrogenase complex (PDC) deficiency impairs brain energy metabolism by reducing the availability of the functional acetylCoA pool. This "hypometabolic defect" results in congenital lactic acidosis and abnormalities of brain morphology and function, ranging from mild ataxia to profound psychomotor retardation. Our previous study showed reduction in total cell number and dendritic arbors in the cerebellar Purkinje cells in systemic PDCdeficient mice. Phenylbutyrate has been shown to increase PDC activity in cultured fibroblasts from PDCdeficient patients. Hence, we investigated the effects of postnatal (days 235) phenylbutyrate administration on the cerebellar Purkinje cell population in PDCdeficient female mice. Histological analyses of different regions of cerebellar cortex from the brainspecific PDCdeficient salineinjected mice revealed statistically significant reduction in the Purkinje cell density and increased cell size of the individual Purkinje cell soma compared to control PDCnormal, salineinjected group. Administration of phenylbutyrate to control mice did not cause significant changes in the Purkinje cell density and cell size in the studied regions. In contrast, administration of phenylbutyrate variably lessened the ill effects of PDC deficiency on Purkinje cell populations in different areas of the cerebellum. Our results lend further support for the possible use of phenylbutyrate as a potential treatment for PDC deficiency.
Assuntos
Encéfalo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fenilbutiratos/farmacologia , Células de Purkinje/efeitos dos fármacos , Animais , Córtex Cerebelar/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos Transgênicos , Fenilbutiratos/metabolismo , Células de Purkinje/citologiaRESUMO
The way hippocampal neurons function during stress in old age (critical times of life) is dependent on brain derived neurotrophin factor (BDNF). This study examined the influence of acute and chronic forced swim (FS) or high-light open field (HLOF) stimulation on the density of BDNF immunoreactive (ir) neurons in the hippocampal pyramidal layers of CA1, CA2, CA3 regions and the granular layer of dentate gyrus (DG) in old (postnatal day 720; P720) Wistar Han rats. Our data showed that in comparison with non-stressed rats, acute FS caused a significant increase in the density of BDNF-ir neurons in CA2 and CA3, while acute HL-OF led to an increase in this factor in all hippocampal subfields with the exception of DG. However, the density of BDNF-ir cells remained unchanged after exposure to chronic FS or HLOF in the hippocampal regions in relation to the control rats. These results indicate that acute FS or HL-OF proved to be a stressor that induces an increase in the density of BDNF-ir pyramidal neurons, which was probably connected with up-regulation of HPA axis activity and shorttime memory processing of the stressful situation. Moreover, as far as the influence on BDNF-ir cells in hippocampus is concerned, chronic FS or HL-OF was not an aggravating factor for rats in the ontogenetic periods studied.