| First Author | Maurin H | Year | 2013 |
| Journal | Mol Brain | Volume | 6 |
| Pages | 27 | PubMed ID | 23705847 |
| Mgi Jnum | J:205083 | Mgi Id | MGI:5543991 |
| Doi | 10.1186/1756-6606-6-27 | Citation | Maurin H, et al. (2013) Neurological characterization of mice deficient in GSK3alpha highlight pleiotropic physiological functions in cognition and pathological activity as Tau kinase. Mol Brain 6:27 |
| abstractText | BACKGROUND: GSK3beta 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 GSK3alpha isozyme remained largely ignored with respect to both aspects. RESULTS: We generated and characterized two mouse strains with neuron-specific or with total GSK3alpha deficiency. Behavioral and electrophysiological analysis demonstrated the physiological importance of neuronal GSK3alpha, with GSK3beta 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, GSK3alpha 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: GSK3alpha proved to be regulated independently from GSK3beta, and to exert non-redundant physiological neurological functions in general behavior and in cognition. Moreover, GSK3alpha contributes to the pathological phosphorylation of protein Tau. |
