Neurological characterization of mice deficient in GSK3α highlight pleiotropic physiological functions in cognition and pathological activity as Tau kinase

Maurin, Hervé and Lechat, Benoit and Dewachter, Ilse and Ris, Laurence and Louis, Justin V and Borghgraef, Peter and Devijver, Herman and Jaworski, Tomasz and Van Leuven, Fred (2013) Neurological characterization of mice deficient in GSK3α highlight pleiotropic physiological functions in cognition and pathological activity as Tau kinase. Molecular Brain, 6 (1). p. 27. ISSN 1756-6606

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Official URL: http://dx.doi.org/10.1186/1756-6606-6-27

Abstract

Background: GSK3β is involved in a wide range of physiological functions, and is presumed to act in the pathogenesis of neurological diseases, from bipolar disorder to Alzheimer’s disease (AD). In contrast, the GSK3α isozyme remained largely ignored with respect to both aspects. Results: We generated and characterized two mouse strains with neuron-specific or with total GSK3α deficiency. Behavioral and electrophysiological analysis demonstrated the physiological importance of neuronal GSK3α, with GSK3β not compensating for impaired cognition and reduced LTP. Interestingly, the passive inhibitory avoidance task proved to modulate the phosphorylation status of both GSK3 isozymes in wild-type mice, further implying both to function in cognition. Moreover, GSK3α contributed to the neuronal architecture of the hippocampal CA1 sub-region that is most vulnerable in AD. Consequently, practically all parameters and characteristics indicated that both GSK3 isoforms were regulated independently, but that they acted on the same physiological functions in learning and memory, in mobility and in behavior. Conclusions: GSK3α proved to be regulated independently from GSK3β, and to exert non-redundant physiological neurological functions in general behavior and in cognition. Moreover, GSK3α contributes to the pathological phosphorylation of protein Tau.

Item Type: Article
Subjects: Pharmaceutical Sciences
Divisions: College of Pharmacy > Pharmaceutical Sciences
Depositing User: Dr Justin Louis
Date Deposited: 03 May 2017 08:07
Last Modified: 03 May 2017 08:07
URI: http://eprints.kku.edu.sa/id/eprint/757

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