TY - JOUR
T1 - Involvement of metabotropic glutamate receptor 5 signaling in activity-related proliferation of adult hippocampal neural stem cells
AU - Nochi, Rokuya
AU - Kato, Tomomasa
AU - Kaneko, Jun
AU - Itou, Yoshie
AU - Kuribayashi, Hiroshi
AU - Fukuda, Satoshi
AU - Terazono, Yasushi
AU - Matani, Ayumu
AU - Kanatani, Shigeaki
AU - Nakajima, Kazunori
AU - Hisatsune, Tatsuhiro
PY - 2012/8
Y1 - 2012/8
N2 - Adult hippocampal neural stem cells can be activated by hippocampal neural activities. When focal cerebral ischemia, known as middle cerebral artery occlusion (MCAO), occurs, neural stem cells are activated to promote their proliferation. However, the mechanism by which these cells are activated is still unclear. Here, we indicate the involvement of metabotropic glutamate receptor 5 (mGluR5) signaling in neural stem cells in their activity-related proliferation after MCAO. We found mGluR5 molecules on neural stem cells by using calcium imaging. We detected the activation of neural stem cells by adding the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine. On a hippocampal slice, the activation of neural stem cells to promote their proliferation was initiated by theta-burst electrical stimulation at the perforant pathway, and this activation was significantly blocked by an mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP). In addition to this, the injection of the blood-brain barrier-permeable mGluR5 agonist 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide into live mice promoted the proliferation of neural stem cells. Moreover, in vivo theta-burst electrical stimulation induced proliferation of neural stem cells. A chronic field recording study showed that the activity of the hippocampal formation was elevated after MCAO. Finally, we observed that the mGluR5 antagonist MPEP significantly blocked the stimulated proliferation of neural stem cells induced by MCAO, by blocking mGluR5 signaling. Our results suggest that glutamates released by the elevated neural activities after MCAO may trigger mGluR5 signaling in neural stem cells to promote their proliferation. Adult hippocampal neural stem cell can be activated by hippocampal neural activities. When focal cerebral ischemia occurs, known as middle cerebral artery occlusion (MCAO), neural stem cells get activated to promote its proliferation.
AB - Adult hippocampal neural stem cells can be activated by hippocampal neural activities. When focal cerebral ischemia, known as middle cerebral artery occlusion (MCAO), occurs, neural stem cells are activated to promote their proliferation. However, the mechanism by which these cells are activated is still unclear. Here, we indicate the involvement of metabotropic glutamate receptor 5 (mGluR5) signaling in neural stem cells in their activity-related proliferation after MCAO. We found mGluR5 molecules on neural stem cells by using calcium imaging. We detected the activation of neural stem cells by adding the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine. On a hippocampal slice, the activation of neural stem cells to promote their proliferation was initiated by theta-burst electrical stimulation at the perforant pathway, and this activation was significantly blocked by an mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP). In addition to this, the injection of the blood-brain barrier-permeable mGluR5 agonist 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide into live mice promoted the proliferation of neural stem cells. Moreover, in vivo theta-burst electrical stimulation induced proliferation of neural stem cells. A chronic field recording study showed that the activity of the hippocampal formation was elevated after MCAO. Finally, we observed that the mGluR5 antagonist MPEP significantly blocked the stimulated proliferation of neural stem cells induced by MCAO, by blocking mGluR5 signaling. Our results suggest that glutamates released by the elevated neural activities after MCAO may trigger mGluR5 signaling in neural stem cells to promote their proliferation. Adult hippocampal neural stem cell can be activated by hippocampal neural activities. When focal cerebral ischemia occurs, known as middle cerebral artery occlusion (MCAO), neural stem cells get activated to promote its proliferation.
KW - Brain ischemia
KW - Calcium imaging
KW - Cell proliferation
KW - MGluR5
KW - Neural stem cell
UR - http://www.scopus.com/inward/record.url?scp=84864827317&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864827317&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2012.08128.x
DO - 10.1111/j.1460-9568.2012.08128.x
M3 - Article
C2 - 22591399
AN - SCOPUS:84864827317
SN - 0953-816X
VL - 36
SP - 2273
EP - 2283
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 3
ER -