Effects of cerebral ischemia in mice deficient in Persephin
AUTOR(ES)
Tomac, Andreas C.
FONTE
The National Academy of Sciences
RESUMO
Persephin (Pspn), a recently cloned member of the transforming growth factor-β superfamily (TGF-β) and glial cell line-derived neurotrophic factor (GDNF) subfamily, is distributed throughout the nervous system at extremely low levels and is thought to function as a survival factor for midbrain dopaminergic and spinal motor neurons in vivo. Here, we report that mice lacking Pspn by homologous recombination show normal development and behavior, but are hypersensitive to cerebral ischemia. A 300% increase in infarction volume was observed after middle cerebral artery occlusion. We find that glutamate-induced Ca2+ influx, thought to be a major component of ischemic neuronal cell death, can be regulated directly by the Persephin protein (PSP) and that PSP can reduce hypoxia/reperfusion cell death in vitro. Neuronal cell death can be prevented or markedly attenuated by administration of recombinant human PSP in vivo before ischemia in both mouse and rat models. Taken together, these data indicate that PSP is a potent modulator of excitotoxicity in the central nervous system with pronounced neuroprotective activity. Our findings support the view that PSP signaling can exert an important control function in the context of stroke and glutamate-mediated neurotoxicity, and also suggest that future therapeutic approaches may involve this novel trophic protein.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=123173Documentos Relacionados
- Anxiolytic-like and proneurogenic effects of Trichilia catigua ethyl-acetate fraction in mice with cerebral ischemia
- Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation
- Cerebral Edema and Cerebral Hemorrhages in Interleukin-10-Deficient Mice Infected with Plasmodium chabaudi
- Effects of physical exercise on skeletal muscles of rats with cerebral ischemia
- Loss of Neurons in the Hippocampus and Cerebral Cortex of AMSH-Deficient Mice