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GLP-1 modulated the firing activity of nigral dopaminergic neurons in both normal and parkinsonian mice.
Liu, Cui; Liu, Wen-Hong; Yang, Wu; Chen, Lei; Xue, Yan; Chen, Xin-Yi.
Afiliación
  • Liu C; Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China; Department of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
  • Liu WH; Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China.
  • Yang W; Department of International Medicine, Affiliated Hospital of Qingdao University, Qingdao, China.
  • Chen L; Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China.
  • Xue Y; Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China.
  • Chen XY; Department of International Medicine, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: caroline_cross@163.com.
Neuropharmacology ; 252: 109946, 2024 Jul 01.
Article en En | MEDLINE | ID: mdl-38599494
ABSTRACT
The spontaneous firing activity of nigral dopaminergic neurons is associated with some important roles including modulation of dopamine release, expression of tyrosine hydroxylase (TH), as well as neuronal survival. The decreased neuroactivity of nigral dopaminergic neurons has been revealed in Parkinson's disease. Central glucagon-like peptide-1 (GLP-1) functions as a neurotransmitter or neuromodulator to exert multiple brain functions. Although morphological studies revealed the expression of GLP-1 receptors (GLP-1Rs) in the substantia nigra pars compacta, the possible modulation of GLP-1 on spontaneous firing activity of nigral dopaminergic neurons is unknown. The present extracellular in vivo single unit recordings revealed that GLP-1R agonist exendin-4 significantly increased the spontaneous firing rate and decreased the firing regularity of partial nigral dopaminergic neurons of adult male C57BL/6 mice. Blockade of GLP-1Rs by exendin (9-39) decreased the firing rate of nigral dopaminergic neurons suggesting the involvement of endogenous GLP-1 in the modulation of firing activity. Furthermore, the PKA and the transient receptor potential canonical (TRPC) 4/5 channels are involved in activation of GLP-1Rs-induced excitatory effects of nigral dopaminergic neurons. Under parkinsonian state, both the exogenous and endogenous GLP-1 could still induce excitatory effects on the surviving nigral dopaminergic neurons. As the mild excitatory stimuli exert neuroprotective effects on nigral dopaminergic neurons, the present GLP-1-induced excitatory effects may partially contribute to its antiparkinsonian effects.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Potenciales de Acción / Sustancia Negra / Péptido 1 Similar al Glucagón / Neuronas Dopaminérgicas / Receptor del Péptido 1 Similar al Glucagón / Exenatida / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Potenciales de Acción / Sustancia Negra / Péptido 1 Similar al Glucagón / Neuronas Dopaminérgicas / Receptor del Péptido 1 Similar al Glucagón / Exenatida / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido