Sensitivity of the S1 neuronal calcium network to insulin and Bay-K 8644 in vivo: Relationship to gait, motivation, and aging processes.

Autor: Lin RL; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA., Frazier HN; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA., Anderson KL; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA., Case SL; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA., Ghoweri AO; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA., Thibault O; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2022 Jul; Vol. 21 (7), pp. e13661. Date of Electronic Publication: 2022 Jun 19.
DOI: 10.1111/acel.13661
Abstrakt: Neuronal hippocampal Ca 2+ dysregulation is a critical component of cognitive decline in brain aging and Alzheimer's disease and is suggested to impact communication and excitability through the activation of a larger after hyperpolarization. However, few studies have tested for the presence of Ca 2+ dysregulation in vivo, how it manifests, and whether it impacts network function across hundreds of neurons. Here, we tested for neuronal Ca 2+ network dysregulation in vivo in the primary somatosensory cortex (S1) of anesthetized young and aged male Fisher 344 rats using single-cell resolution techniques. Because S1 is involved in sensory discrimination and proprioception, we tested for alterations in ambulatory performance in the aged animal and investigated two potential pathways underlying these central aging- and Ca 2+ -dependent changes. Compared to young, aged animals displayed increased overall activity and connectivity of the network as well as decreased ambulatory speed. In aged animals, intranasal insulin (INI) increased network synchronicity and ambulatory speed. Importantly, in young animals, delivery of the L-type voltage-gated Ca 2+ channel modifier Bay-K 8644 altered network properties, replicating some of the changes seen in the older animal. These results suggest that hippocampal Ca 2+ dysregulation may be generalizable to other areas, such as S1, and might engage modalities that are associated with locomotor stability and motivation to ambulate. Further, given the safety profile of INI in the clinic and the evidence presented here showing that this central dysregulation is sensitive to insulin, we suggest that these processes can be targeted to potentially increase motivation and coordination while also reducing fall frequency with age.
(© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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