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1.
Cells ; 12(4)2023 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-36831327

RESUMO

The vitamin D receptor (VDR) belongs to the nuclear receptor superfamily of transcription factors. The VDR is expressed in diverse brain regions and has been implicated in the neuroprotective, antiaging, prosurvival, and anti-inflammatory action of vitamin D. Accordingly, a relationship between vitamin D insufficiency and susceptibility to neurodegenerative diseases has been suggested. However, due to the multitargeted mechanisms of vitamin D and its often overlapping genomic and nongenomic effects, the role of the VDR in brain pathologies remains obscure. In this narrative review, we present progress in deciphering the molecular mechanism of nuclear VDR-mediated vitamin D effects on prosurvival and anti-inflammatory signaling pathway activity within the central nervous system. In line with the concept of the neurovascular unit in pathomechanisms of neurodegenerative diseases, a discussion of the role of the VDR in regulating the immune and vascular brain systems is also included. Next, we discuss the results of preclinical and clinical studies evaluating the significance of vitamin D status and the efficacy of vitamin D supplementation in the treatment of Parkinson's and Alzheimer's diseases, emphasizing the possible role of the VDR in these phenomena. Finally, the associations of some VDR polymorphisms with higher risks and severity of these neurodegenerative disorders are briefly summarized.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Receptores de Calcitriol/metabolismo , Doença de Parkinson/genética , Vitamina D/metabolismo , Vitaminas
2.
Pharmacol Rep ; 71(2): 338-346, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30831439

RESUMO

BACKGROUND: In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex - brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions. METHODS: Adult male PS rats were subjected to acute stress and/or received orally glucose. Levels of hormones and their receptors were assayed with ELISA method. In vitro studies were performed on mHypoA-2/12 hypothalamic cell line, stably transfected with CRH promoter coupled with luciferase. RESULTS: PS has reduced GLP-1 and GLP-1R levels, attenuated glucose-induced increase in insulin concentration and increased the amount of phosphorylated IR in the hypothalamus of animals subjected to additional stress stimuli, and also decreased the GLP-1R level in the hippocampus. In vitro studies demonstrated that insulin is capable of increasing CRH promoter activity in the condition of stimulation of the cAMP/PKA pathway in the applied cellular model. CONCLUSION: Prenatal stress may act as a preconditioning factor, affecting the concentrations of hormones such as insulin and GLP-1 in the hypothalamus in response to adverse stimuli. The decreased GLP-1R level in the hippocampus could be linked with the disturbances in neuronal plasticity.


Assuntos
Depressão/fisiopatologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipotálamo/metabolismo , Insulina/metabolismo , Animais , Linhagem Celular , Hormônio Liberador da Corticotropina/genética , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Exenatida/metabolismo , Feminino , Glucose/metabolismo , Masculino , Camundongos , Plasticidade Neuronal/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Regiões Promotoras Genéticas/genética , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/fisiopatologia
3.
Psychoneuroendocrinology ; 60: 151-62, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26143539

RESUMO

Currently, much attention is focused on the influence of mitochondrial disturbances at the onset of depression. The goal of this study was to investigate the impact of prenatal stress (an animal model of depression) on the mitochondrial biogenesis proteins and mitoproteome profile in the frontal cortex and hippocampus of adult 3-month-old male rats following a prenatal stress procedure. Our results show that rats that were exposed to prenatal stress stimuli displayed depression-like behaviors based on the sucrose preference and elevated plus maze tests. It has been found that the level of the PGC-1α protein was reduced in the frontal cortex and hippocampus of the adult offspring after the prenatal stress procedure. Moreover, in the frontal cortex, the level of the pro-apoptotic protein Bax was up-regulated. Two-dimensional electrophoresis coupled with mass spectrometry showed the statistically significant down-regulation of the mitochondrial ribosomal protein L12 (Mrpl12) and mitochondrial NADH dehydrogenase [ubiquinone] flavoprotein 2 (NDUFV2) as well as the up-regulation of the Tubulin Polymerization Promoting Proteins (Tppp/p25) in the frontal cortex. In contrast, in the hippocampus, the mitochondrial pyruvate dehydrogenase E1 component subunit beta, the voltage-dependent anion-selective channel protein 2 (VDAC2), and the GTP-binding nuclear protein RAN (RAN) were down-regulated and the expression of phosphatidylethanolamine-binding protein 1 (PEBP-1) was enhanced. These findings provide new evidence that stress during pregnancy may lead not only to behavioral deficits, but also to disturbances in the brain mitoproteome profile in adult rat offspring.


Assuntos
Lobo Frontal/metabolismo , Hipocampo/metabolismo , Proteínas Mitocondriais/biossíntese , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estresse Psicológico/psicologia , Animais , Ansiedade/psicologia , Depressão/psicologia , Feminino , Preferências Alimentares , Masculino , Mitocôndrias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Gravidez , Proteômica , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo , Proteína X Associada a bcl-2/metabolismo
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