AUTHOR=Takashima Akihiko 

TITLE=GSK-3β and memory formation

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 5 - 2012

YEAR=2012

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2012.00047

DOI=10.3389/fnmol.2012.00047

ISSN=1662-5099

ABSTRACT=In Alzheimer’s disease (AD), tau hyperphosphorylation and neurofibrillary tangle (NFT) formation are strongly associated with dementia.  Memory impairment is a characteristic,   early symptom of AD.   Glycogen synthase kinase 3 β (GSK-3β), which is activated in response to amyloid β (Aβ) formation, and the normal process of aging, hyperphosphorylates tau present in the NFTs.  Furthermore, activation of GSK-3β inhibits synaptic long-term potentiation (LTP) through tau.  It is therefore likely, that activation of GSK-3β is responsible for the memory problems seen in both advanced age, and AD.  Indeed, inhibition of GSK-3 by lithium halts the progression of symptoms in patients with mild cognitive impairment (MCI).  However, long-term treatment of lithium increases the risk of dementia in old age, in bipolar patients.  To understand the role of GSK-3β in brain function, we analyzed memory formation in GSK-3β heterozygote, knockout mice.  Results indicate that these mice show impaired memory reconsolidation.  It would seem that activation of GSK-3β is required for memory maintenance, with a higher requirement as animals age, and the volume of memory increases. This in turn causes exaggerated activation of GSK-3β, leading to memory problems, and the formation of NFTs.