Polysialylation of NCAM is upregulated by hyperthermia and participates in heat shock preconditioning-induced neuroprotection.
"Brain tolerance"--a phenomenon in which a subtoxic challenge confers resistance to subsequent brain injuries--provides an ideal opportunity for investigating endogenous neuroprotective mechanisms. We investigated the potential role of the polysialylated (PSA) form of neural cell adhesion molecule (NCAM), which is thought to play a key role in plasticity. In a model where prior exposure to heat shock protects against kainate-induced cell damage in the hippocampus, we show that hyperthermia upregulates PSA-NCAM expression for at least 1 week, without affecting neurogenesis. Pharmacological manipulation of heat shock protein (HSP) expression demonstrates a tight positive link between HSP70 and PSA-NCAM. Finally, the presence of PSA was functionally linked to brain tolerance, as protection against kainate-induced cell death by heat shock pre-exposure was abolished in the absence of NCAM polysialylation. The upregulation of PSA-NCAM by hyperthermia may have a significant impact on hippocampal plasticity, permitting induction of the complex molecular cascade responsible for neuroprotection.
Duveau
V
V
Université Bordeaux 2, CNRS UMR 5227-Mouvement, Adaptation, Cognition, 146, rue Léo Saignat, 33076 Bordeaux Cedex, France.
Arthaud
S
S
Rougier
A
A
Le Gal La Salle
G
G
D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001925:Brain Damage, Chronic / Q000378:metabolism* / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000502:physiology*; D005334:Fever / Q000378:metabolism* / Q000503:physiopathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D018840:HSP70 Heat-Shock Proteins; D039842:Neural Cell Adhesion Molecule L1; D009498:Neurotoxins; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule