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Memory formation in old age requires GSK-3β

Riki Koike1, Yuta Takaichi2, Yoshiyuki Soeda1

  • 1Laboratory for Alzheimer's Disease, Department of Life Science, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan.

Aging Brain
|March 13, 2023
PubMed

Insights

Glycogen synthase kinase 3β (GSK-3β) is crucial for memory in aging mice. Reduced GSK-3β impairs both short-term and long-term memory, suggesting a role in maintaining brain function during aging.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Aging Research

Background:

  • Glycogen synthase kinase 3β (GSK-3β) is implicated in neurodegenerative diseases like Alzheimer's disease (AD).
  • GSK-3β is linked to tau hyperphosphorylation and amyloid-beta (Aβ) production, key pathological hallmarks of AD.
  • Clinical trials inhibiting GSK-3β in AD patients showed limited cognitive benefits.

Purpose of the Study:

  • To investigate the physiological role of GSK-3β in memory formation during old age.
  • To understand why GSK-3β inhibition failed to improve cognitive function in AD patients.

Main Methods:

  • Utilized a contextual fear-conditioning paradigm in old mice.
  • Performed biochemical and immunohistochemical analyses on gsk-3β+/- and wild-type (wt) littermate mice.

Main Results:

  • Old gsk-3β+/- mice exhibited deficits in both short-term and long-term memory formation.
  • Synapse numbers were comparable between gsk-3β+/- and wt mice, indicating GSK-3β's role is not dependent on synapse count.

Conclusions:

  • GSK-3β is essential for memory formation in aged mice.
  • GSK-3β may play a vital role in maintaining brain function throughout the aging process.
  • These findings may explain the limited efficacy of GSK-3β inhibitors in AD patients.
Keywords:
AgingAlzheimer's diseaseConsolidationGSK-3βMemory

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