CD44 Deficiency Is Associated with Increased Susceptibility to Stress-Induced Anxiety-like Behavior in Mice

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

CD44 is a cell surface adhesion molecule and its principal ligand is hyaluronic acid (HA), a key component of the brain’s extracellular matrix. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in genome wide association study as a possible risk gene in suicidal behavior. In order to define the pathobiological mechanisms by which CD44 may affect behavior, we investigated the role of CD44 using male CD44 knockout (CD44KO) and wild-type mice that underwent chronic mild stress (CMS). Behavior was characterized using the sucrose preference and forced swim tests, open field, novel object recognition, social preference, and the elevated plus maze tests. Gene expression in hippocampus was evaluated using quantitative real-time PCR. Brain monoamines and their metabolites were assessed by high-performance liquid chromatography and serum HA and IL-1β levels were measured using ELISA and electrochemiluminescence assays. CD44KO mice were more susceptible to stress-induced anxiety-like behavior and displayed increased anhedonia and despair than the wild-type controls. The behavioral phenotype of stressed CD44KO mice was associated with reduced cortical serotonergic and striatal dopaminergic turnover. The hippocampal expression of the receptor for HA-mediated motility (RHAMM) was reduced in the non- stressed CD44KO mice compared with WT mice, in a value similar to that observed in WT mice following exposure to stress. Taken together, our experiments suggest that CD44 plays a key role in stress response in mice.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Hebrew University of Jerusalem
  • Michigan State University
  • Tel-Aviv University
  • Van Andel Research Institute
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper

Nyckelord

Originalspråkengelska
Sidor (från-till)548-558
TidskriftJournal of Molecular Neuroscience : MN
Volym60
Utgivningsnummer4
Tidigt onlinedatum2016 sep 13
StatusPublished - 2016 dec
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Filip Ventorp, 2017, Lund: Lund University, Faculty of Medicine. 111 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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