ERIC Number: EJ1067960
Record Type: Journal
Publication Date: 2015-Jul
Abstractor: As Provided
Inhibition of Glycogen Synthase Kinase-3ß Enhances Cognitive Recovery after Stroke: The Role of TAK1
Venna, Venugopal Reddy; Benashski, Sharon E.; Chauhan, Anjali; McCullough, Louise D.
Learning & Memory, v22 n7 p336-343 Jul 2015
Memory deficits are common among stroke survivors. Identifying neuroprotective agents that can prevent memory impairment or improve memory recovery is a vital area of research. Glycogen synthase kinase-3ß (GSK-3ß) is involved in several essential intracellular signaling pathways. Unlike many other kinases, GSK-3ß is active only when dephosphorylated and activation promotes inflammation and apoptosis. In contrast, increased phosphorylation leads to reduced GSK-3ß (pGSK-3ß) activity. GSK-3ß inhibition has beneficial effects on memory in other disease models. GSK-3ß regulates both the 5'AMP-activated kinase (AMPK) and transforming growth factor-ß-activated kinase (TAK1) pathways. In this work, we examined the effect of GSK-3ß inhibition, both independently, in conjunction with a TAK inhibitor, and in AMPK-a2 deficient mice, after stroke to investigate mechanistic interactions between these pathways. GSK-3ß inhibition was neuroprotective and ameliorated stroke-induced cognitive impairments. This was independent of AMPK signaling as the protective effects of GSK-3ß inhibition were seen in AMPK deficient mice. However, GSK-3ß inhibition provided no additive protection in mice treated with a TAK inhibitor suggesting that TAK1 is an upstream regulator of GSK-3ß. Targeting GSK-3ß could be a novel therapeutic strategy for post-stroke cognitive deficits.
Descriptors: Memory, Neurological Impairments, Brain, Neurological Organization, Inhibition, Animals, Executive Function, Research, Cognitive Ability, Rehabilitation
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Publication Type: Journal Articles; Reports - Research
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