RESUMO
The intracerebroventicular administration (i.c.v.) of glucagon-like peptide-2 (GLP-2) had antidepressant-like effects on saline-treated mice in the forced-swim test. The GLP-2 treatment (3 µg, i.c.v.) for 6 days, but not that of imipramine had antidepressant-like effects on adrenocorticotropic hormone (ACTH)-treated mice. The immunohistochemical detection of the c-fos protein (Fos) revealed that the administration of GLP-2 induced Fos-immunoreactivity (Fos-IR) in the dorsomedial hypothalamic nucleus in saline-treated and ACTH-treated mice, and also in the hippocampal dentate gyrus in ACTH-treated mice, but not in saline-treated mice. In contrast, Fos-IR in the paraventricular nucleus of the hypothalamus decreased after the administration of GLP-2 to ACTH-treated mice. In ACTH-treated mice, the chronic administration of GLP-2 affected hippocampal neurogenesis, in addition to Fos-IR in hypothalamic GABAergic neurons and corticotrophin-releasing factor-containing neurons. These results suggest that GLP-2 acts on specific brain regions to regulate stress conditions, and induces antidepressant-like effects under imipramine-resistant conditions, which may be associated with the modulation of the hypothalamic-pituitary-adrenal-axis.
Assuntos
Antidepressivos/farmacologia , Peptídeo 2 Semelhante ao Glucagon/metabolismo , Hipotálamo/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Animais , Hormônio Liberador da Corticotropina/metabolismo , Imuno-Histoquímica/métodos , Masculino , Camundongos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismoRESUMO
Children with type 1 diabetes mellitus (DM) are at risk of developing cognitive difficulties. Although a diabetes onset of patient influences cognitive difficulties, synaptic properties related to the age of diabetes onset remain unknown. Here we showed that synaptic plasticity including long-term potentiation (LTP) or long-term depression (LTD), and excitatory synaptic transmission at Schaffer collateral-CA1 (SC-CA1) synapses in hippocampal slices were affected by age of onset in rats with streptozotocin-induced diabetes (STZ-rats), compared with age-matched control rats. LTP was impaired and the ratio of AMPA receptor-mediated EPSCs relative to N-methyl-d-aspartate (NMDA) receptor-mediated EPSCs (the AMPA/NMDA ratio) decreased in young adult-onset STZ-rats, whereas LTD was impaired and both AMPA receptor-mediated and NMDA receptor-mediated EPSCs increased in juvenile-onset STZ-rats. Furthermore, impaired LTD of juvenile-onset STZ-rats was restored with an NMDA receptor antagonist. These results suggest that the pathophysiology of diabetes-induced cognitive difficulties varies with the age of diabetes onset.
Assuntos
Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Hipocampo/citologia , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/fisiologia , Estreptozocina/toxicidade , Sinapses/efeitos dos fármacos , Fatores Etários , Idade de Início , Análise de Variância , Animais , Animais Recém-Nascidos , Biofísica , Modelos Animais de Doenças , Estimulação Elétrica , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Antagonistas GABAérgicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Vias Neurais/fisiopatologia , Plasticidade Neuronal/fisiologia , Técnicas de Patch-Clamp , Picrotoxina/farmacologia , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Receptores de Glutamato/metabolismo , Sinapses/fisiologia , Valina/análogos & derivados , Valina/farmacologiaRESUMO
Proglucagon-derived glucagon-like peptide-2 (GLP-2) is released from enteroendocrine cells and neurons. GLP-2 regulates energy absorption and epithelial integrity in the gastrointestinal tract, but its effect on blood-pressure regulation remains unknown. In the present study, we found that GLP-2 administered both peripherally and centrally dose-dependently reduced mean arterial blood pressure (MAP) in male Wistar rats anesthetized with urethane and α-chloralose. Immunohistochemical detection of the c-fos protein (Fos) revealed that the peripherally and centrally administered GLP-2 induced Fos-immunoreactivity (Fos-IR) in the nucleus of the solitary tract (NTS) and the caudal ventrolateral medulla (CVLM). In contrast, Fos-IR in brainstem catecholamine neurons decreased after the administration of GLP-2. These results suggest that GLP-2 acts on specific brain nuclei to inhibit sympathetic nerve activity and this leads to hypotension.