Reelin changes hippocampal learning in aging and Alzheimer's disease

Austin T. Marckx, Katja E. Fritschle, Laurent Calvier, Joachim Herz

Research output: Contribution to journalArticlepeer-review

Abstract

The hippocampal formation (HF) is a neuroanatomical region essential for learning and memory. As one of the earliest regions to display the histopathological hallmarks of Alzheimer's disease (AD), determining the specific mechanisms of the HF's vulnerability is of capital importance. Reelin, a glycoprotein crucial in cortical lamination during embryonic neurogenesis, has an uncommon expression pattern within the HF and has been implicated in both learning and AD pathogenesis. We hypothesized that Reelin deficiency would expedite behavioral impairments which accompany normal aging. Additionally, we hypothesized that Reelin deficiency in the presence of mutated human microtubule associated protein tau (MAPT) would further impair hippocampal function. To test our hypothesis, we utilized cohorts of aged mice, aged mice with Reelin conditional knockout (RcKO), and adult mice with both RcKO and MAPT in the Barnes maze and Trace fear conditioning. Consistent with prior literature, increased age in wild-type mice was sufficient to reduce spatial searching in the Barnes maze. Increased age both exacerbated spatial impairments and altered context learning in RcKO mice. Lastly, adult mice with both RcKO and the MAPT transgene displayed both the lowest age-of-onset and most severe spatial learning deficits. In conclusion, Reelin deficiency when combined with AD risk-factors produced consistent impairments in spatial memory tasks. Furthermore, our results further implicate Reelin's importance in both HF homeostasis and AD pathogenesis.

Original languageEnglish (US)
Article number113482
JournalBehavioural Brain Research
Volume414
DOIs
StatePublished - Sep 24 2021

Keywords

  • Aging
  • Alzheimer's disease
  • Barnes maze
  • PS19
  • Reelin
  • Trace fear conditioning

ASJC Scopus subject areas

  • Behavioral Neuroscience

Fingerprint

Dive into the research topics of 'Reelin changes hippocampal learning in aging and Alzheimer's disease'. Together they form a unique fingerprint.

Cite this