Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats
- PMID: 10574963
- DOI: 10.1074/jbc.274.49.34893
Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats
Abstract
Evidence accumulated from clinical and basic research has indirectly implicated the insulin receptor (IR) in brain cognitive functions, including learning and memory (Wickelgren, I. (1998) Science 280, 517-519). The present study investigates correlative changes in IR expression, phosphorylation, and associated signaling molecules in the rat hippocampus following water maze training. Although the distribution of IR protein matched that of IR mRNA in most forebrain regions, a dissociation of the IR mRNA and protein expression patterns was found in the cerebellar cortex. After training, IR mRNA in the CA1 and dentate gyrus of the hippocampus was up-regulated, and there was increased accumulation of IR protein in the hippocampal crude synaptic membrane fraction. In the CA1 pyramidal neurons, changes in the distribution pattern of IR in particular cellular compartments, such as the nucleus and dendritic regions, was observed only in trained animals. Although IR showed a low level of in vivo tyrosine phosphorylation, an insulin-stimulated increase of in vitro Tyr phosphorylation of IR was detected in trained animals, suggesting that learning may induce IR functional changes, such as enhanced receptor sensitivity. Furthermore, a training-induced co-immunoprecipitation of IR with Shc-66 was detected, along with changes in in vivo Tyr phosphorylation of Shc and mitogen-activated protein kinase, as well as accumulation of Shc-66, Shc-52, and Grb-2 in hippocampal synaptic membrane fractions following training. These findings suggest that IR may participate in memory processing through activation of its receptor Tyr kinase activity, and they suggest possible engagement of Shc/Grb-2/Ras/mitogen-activated protein kinase cascades.
Similar articles
-
Inputs and outputs of insulin receptor.Protein Cell. 2014 Mar;5(3):203-13. doi: 10.1007/s13238-014-0030-7. Epub 2014 Mar 16. Protein Cell. 2014. PMID: 24633815 Free PMC article. Review.
-
Regulation of insulin receptor function.Cell Mol Life Sci. 2007 Apr;64(7-8):873-91. doi: 10.1007/s00018-007-6359-9. Cell Mol Life Sci. 2007. PMID: 17347799 Free PMC article. Review.
-
Insulin receptor signaling in long-term memory consolidation following spatial learning.Learn Mem. 2005 Nov-Dec;12(6):646-55. doi: 10.1101/lm.88005. Epub 2005 Nov 14. Learn Mem. 2005. PMID: 16287721 Free PMC article.
-
Functional importance of Shc tyrosine 317 on insulin signaling in Rat1 fibroblasts expressing insulin receptors.J Biol Chem. 1997 Apr 4;272(14):9581-6. doi: 10.1074/jbc.272.14.9581. J Biol Chem. 1997. PMID: 9083103
-
Insulin-induced egr-1 and c-fos expression in 32D cells requires insulin receptor, Shc, and mitogen-activated protein kinase, but not insulin receptor substrate-1 and phosphatidylinositol 3-kinase activation.J Biol Chem. 1996 Nov 22;271(47):30222-6. doi: 10.1074/jbc.271.47.30222. J Biol Chem. 1996. PMID: 8939974
Cited by
-
The complex relationship between obesity and neurodegenerative diseases: an updated review.Front Cell Neurosci. 2023 Nov 9;17:1294420. doi: 10.3389/fncel.2023.1294420. eCollection 2023. Front Cell Neurosci. 2023. PMID: 38026693 Free PMC article. Review.
-
Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer's Disease.Neurol Int. 2023 Oct 10;15(4):1253-1272. doi: 10.3390/neurolint15040079. Neurol Int. 2023. PMID: 37873836 Free PMC article. Review.
-
Altered pattern separation in Goto-Kakizaki rats.Curr Res Neurobiol. 2023 Mar 17;4:100082. doi: 10.1016/j.crneur.2023.100082. eCollection 2023. Curr Res Neurobiol. 2023. PMID: 37397815 Free PMC article.
-
Dementia in Diabetes: The Role of Hypoglycemia.Int J Mol Sci. 2023 Jun 7;24(12):9846. doi: 10.3390/ijms24129846. Int J Mol Sci. 2023. PMID: 37372995 Free PMC article. Review.
-
Cardiometabolic health, menopausal estrogen therapy and the brain: How effects of estrogens diverge in healthy and unhealthy preclinical models of aging.Front Neuroendocrinol. 2023 Jul;70:101068. doi: 10.1016/j.yfrne.2023.101068. Epub 2023 Apr 13. Front Neuroendocrinol. 2023. PMID: 37061205 Free PMC article. Review.
MeSH terms
Substances
Associated data
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous