Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.
In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death.
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. abelousov@kumc.edu
Andrei B
AB
Belousov
Yongfu
Y
Wang
Ji-Hoon
JH
Song
Janna V
JV
Denisova
Nancy E
NE
Berman
Joseph D
JD
Fontes
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D017630:Connexins / Q000235:genetics*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D000097004:Gap Junction delta-2 Protein
D017630:Connexins; D018094:Receptors, Metabotropic Glutamate; D000097004:Gap Junction delta-2 Protein