Sex-dependent modulation of age-related cognitive decline by the L-type calcium channel gene Cacna1c (Cav1.2)

Panos Zanos, Shambhu Bhat, Chantelle E. Terrillion, Robert J. Smith, Leonardo H. Tonelli, Todd D. Gould

Research output: Contribution to journalArticlepeer-review


Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age-related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex-dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age-related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age-related contextual memory declines.

Original languageEnglish (US)
Pages (from-to)2499-2507
Number of pages9
JournalEuropean Journal of Neuroscience
Issue number8
StatePublished - Oct 2015
Externally publishedYes


  • Ageing
  • Cognition
  • Hippocampus
  • Memory
  • Mice

ASJC Scopus subject areas

  • Neuroscience(all)


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