RESUMO
Retinoic acid induced 1 (RAI1) is a protein of uncertain mechanism of action which nevertheless has been the focus of attention because it is a major contributing factor in several human developmental disorders including Smith-Magenis and Potocki-Lupski syndromes. Further, RAI1 may be linked to adult neural disorders with developmental origins such as schizophrenia and autism. The protein has been extensively examined in the rodent but very little is known about its distribution in the human central nervous system. This study demonstrated the presence of RAI1 transcript in multiple regions of the human brain. The cellular expression of RAI1 protein in the human brain was found to be similar to that described in the mouse, with high levels in neurons, but not glia, of the dentate gyrus and cornus ammonis of the hippocampus. In the cerebellum, a second region of high expression, RAI1 was present in Purkinje cells, but not granule cells. RAI1 was also found in neurons of the occipital cortex. The expression of this retinoic acid-induced protein matched well in the hippocampus with expression of the retinoic acid receptors. The subcellular distribution of human neuronal RAI1 indicated its presence in both cytoplasm and nucleus. Overall, human RAI1 protein was found to be a highly expressed neuronal protein whose distribution matches well with its role in cognitive and motor skills.
Assuntos
Cerebelo/química , Hipocampo/química , Doenças do Sistema Nervoso/metabolismo , Neurônios/química , Lobo Occipital/química , Fatores de Transcrição/análise , Cerebelo/patologia , Cognição , Regulação da Expressão Gênica , Hipocampo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Destreza Motora , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/psicologia , Lobo Occipital/fisiopatologia , Células de Purkinje/química , RNA Mensageiro/análise , Transdução de Sinais , Transativadores , Fatores de Transcrição/genéticaAssuntos
Declaração de Nascimento , Clima , Esclerose Múltipla/epidemiologia , Feminino , Humanos , MasculinoRESUMO
Retinoic acid, the active form of the nutrient vitamin A, regulates several facets of neuronal plasticity in the hippocampus, including neurogenesis and synaptic strength, acting via specific retinoic acid receptors (RARs). Essential for conversion of vitamin A to retinoic acid is the enzyme retinaldehyde dehydrogenase (RALDH) and in the rodent hippocampus this is only present in the adjacent meninges where it must act as a locally released paracrine hormone. Little is known though about the expression of RALDHs and RARs in the human hippocampus. This study confirms that RALDH levels are very low in mouse neurons but, surprisingly, strong expression of RALDH protein is detected by immunohistochemistry in hippocampal neurons. The receptors RARα, ß and γ were also detected, each receptor exhibiting differing subcellular locations implying their potential regulation of both transcription and non-genomic actions. These results imply an essential function of retinoic acid in the human hippocampus likely to include regulation of neuronal plasticity.