期刊
NEUROSCIENCE
卷 374, 期 -, 页码 104-118出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2018.01.041
关键词
Alzheimer's disease; beta-amyloid; hippocampus; IGF-I; protein kinase A; somatostatin
资金
- Fondos de Investigacion Sanitaria
- Fondos FEDER [PI16/00485]
- Ministerio de Ciencia e Innovacion [BFU 2014-51836-C2-2-R]
- Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CIBEROBN)
- Fundacion Endocrinologia y Nutricion
- CIBEROBN
Somatostatin (SRIF), a neuropeptide highly distributed in the hippocampus and involved in learning and memory, is markedly reduced in the brain of Alzheimer's disease patients. The effects of insulin-like growth factor-I (IGF-I) against beta amyloid (A beta)-induced neuronal death and associated cognitive disorders have been extensively reported in experimental models of this disease. Here, we examined the effect of IGF-I on the hippocampal somatostatinergic system in A beta-treated rats and the molecular mechanisms associated with changes in this peptidergic system. Intracerebroventricular A beta 25-35 administration during 14 days (300 pmol/day) to male rats increased A beta 25-35 levels and cell death and markedly reduced SRIF and SRIF receptor 2 levels in the hippocampus. These deleterious effects were associated with reduced Akt and cAMP response element-binding protein (CREB) phosphorylation and activation of c-Jun N-terminal kinase (JNK). Subcutaneous IGF-I co-administration (50 mg/kg/day) reduced hippocampal A beta 25-35 levels, cell death and JNK activation. In addition, IGF-I prevented the reduction in the components of the somatostatinergic system affected by A beta infusion. Its co-administration also augmented protein kinase A (PKA) activity, as well as Akt and CREB phosphorylation. These results suggest that IGF-I co-administration may have protective effects on the hippocampal somatostatinergic system against A beta insult through up-regulation of PKA activity and Akt and CREB phosphorylation. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
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