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Activation of TGR5 Ameliorates Streptozotocin-Induced Cognitive Impairment by Modulating Apoptosis, Neurogenesis, and Neuronal Firing.
Mu, Ronghao; Wu, Xian; Yuan, Danhua; Zhao, Jiajia; Tang, Susu; Hong, Hao; Long, Yan.
Afiliación
  • Mu R; Department of Pharmacology, Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing 211198, China.
  • Wu X; Department of Pharmacology, Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing 211198, China.
  • Yuan D; School of Pharmacy, The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei 230032, China.
  • Zhao J; Department of Pharmacology, Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing 211198, China.
  • Tang S; Department of Pharmacology, Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing 211198, China.
  • Hong H; Department of Pharmacology, Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing 211198, China.
  • Long Y; Department of Pharmacology, Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing 211198, China.
Oxid Med Cell Longev ; 2022: 3716609, 2022.
Article en En | MEDLINE | ID: mdl-35464765
Takeda G protein-coupled receptor 5 (TGR5) is the first known G protein-coupled receptor specific for bile acids and is recognized as a new and critical target for type 2 diabetes and metabolic syndrome. It is expressed in many brain regions associated with memory such as the hippocampus and frontal cortex. Here, we hypothesize that activation of TGR5 may ameliorate streptozotocin- (STZ-) induced cognitive impairment. The mouse model of cognitive impairment was established by a single intracerebroventricular (ICV) injection of STZ (3.0 mg/kg), and we found that TGR5 activation by its agonist INT-777 (1.5 or 3.0 µg/mouse, ICV injection) ameliorated spatial memory impairment in the Morris water maze and Y-maze tests. Importantly, INT-777 reversed STZ-induced downregulation of TGR5 and glucose usage deficits. Our results further showed that INT-777 suppressed neuronal apoptosis and improved neurogenesis which were involved in tau phosphorylation and CREB-BDNF signaling. Moreover, INT-777 increased action potential firing of excitatory pyramidal neurons in the hippocampal CA3 and medial prefrontal cortex of ICV-STZ groups. Taken together, these findings reveal that activation of TGR5 has a neuroprotective effect against STZ-induced cognitive impairment by modulating apoptosis, neurogenesis, and neuronal firing in the brain and TGR5 might be a novel and potential target for Alzheimer's disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Enfermedad de Alzheimer / Disfunción Cognitiva Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Oxid Med Cell Longev Asunto de la revista: METABOLISMO Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Enfermedad de Alzheimer / Disfunción Cognitiva Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Oxid Med Cell Longev Asunto de la revista: METABOLISMO Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos