Heat shock protein 27 delivered via a herpes simplex virus vector can protect neurons of the hippocampus against kainic-acid-induced cell loss.
Heat shock proteins are expressed in response to cellular stress and can protect cells from further stress and facilitate recovery. Heat shock protein 27 is of particular interest because it has been implicated in a range of protective roles including protein chaperoning, stabilising elements of the cytoskeleton and as an active inhibitor of apoptosis. In the present study, we have examined the potential of administration of exogenous HSP27 to confer protection against KA-induced neuronal cell death in vivo. We aimed to exploit the neurotropic specificity of herpes simplex virus-1 based virus vectors, which have been rendered replication-incompetent, to infect neurons of the hippocampus. The systemic administration of kainic acid, an analogue of glutamate, causes seizures resulting in neuronal damage and is an established animal model of epilepsy. Neuron loss is particularly prominent in the hippocampus and the mode of death is at least partly apoptotic in nature. We show that the overexpression of HSP27 in these neurons can significantly augment their survival following kainic acid administration. In contrast, injection of a control virus expressing beta-galactosidase does not confer protection. This is the first time that protection by exogenously expressed HSP27 has been demonstrated in an in vivo model of neuronal cell death.
Kalwy
Stephan A
SA
Institute of Child Health, University College London, 30 Guilford St., London WC1 1EH, UK.
Akbar
Mohammed T
MT
Coffin
Robert S
RS
de Belleroche
Jacqueline
J
Latchman
David S
DS
D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors / Q000494:pharmacology* / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D013312:Stress, Physiological / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D007608:Kainic Acid