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Novel calcium-related targets of insulin in hippocampal neurons
- Source :
- Neuroscience. 364
- Publication Year :
- 2017
-
Abstract
- Both insulin signaling disruption and Ca 2+ dysregulation are closely related to memory loss during aging and increase the vulnerability to Alzheimer’s disease (AD). In hippocampal neurons, aging-related changes in calcium regulatory pathways have been shown to lead to higher intracellular calcium levels and an increase in the Ca 2+ -dependent afterhyperpolarization (AHP), which is associated with cognitive decline. Recent studies suggest that insulin reduces the Ca 2+ -dependent AHP. Given the sensitivity of neurons to insulin and evidence that brain insulin signaling is reduced with age, insulin-mediated alterations in calcium homeostasis may underlie the beneficial actions of insulin in the brain. Indeed, increasing insulin signaling in the brain via intranasal delivery has yielded promising results such as improving memory in both clinical and animal studies. However, while several mechanisms have been proposed, few have focused on regulation on intracellular Ca 2+ . In the present study, we further examined the effects of acute insulin on calcium pathways in primary hippocampal neurons in culture. Using the whole-cell patch-clamp technique, we found that acute insulin delivery reduced voltage-gated calcium currents. Fura-2 imaging was used to also address acute insulin effects on spontaneous and depolarization-mediated Ca 2+ transients. Results indicate that insulin reduced Ca 2+ transients, which appears to have involved a reduction in ryanodine receptor function. Together, these results suggest insulin regulates pathways that control intracellular Ca 2+ which may reduce the AHP and improve memory. This may be one mechanism contributing to improved memory recall in response to intranasal insulin therapy in the clinic.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Aging
SERCA
Patch-Clamp Techniques
medicine.medical_treatment
chemistry.chemical_element
Calcium
Hippocampus
Calcium in biology
Article
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Internal medicine
Medicine
Animals
Insulin
Cells, Cultured
Calcium metabolism
Neurons
biology
business.industry
Ryanodine receptor
General Neuroscience
Afterhyperpolarization
Rats
Insulin receptor
030104 developmental biology
Endocrinology
chemistry
biology.protein
business
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 18737544
- Volume :
- 364
- Database :
- OpenAIRE
- Journal :
- Neuroscience
- Accession number :
- edsair.doi.dedup.....ade5d36867500b2af80453a5db009570