title: mGluR5-PLCbeta4-PKCbeta2/PKCgamma pathways in hippocampal CA1 pyramidal neurons in pilocarpine model of status epilepticus in mGluR5+/+ mice.
abstract: While it is generally accepted that phospholipase C (PLC) and protein kinase C (PKC) are down-stream proteins involved in metabotropic glutamate receptor 5 (mGluR5)-related signal transduction, we still do not know which subtype of PLC or PKC is specifically regulated after mGluR5 activation. In the present study in mGluR5 wild-type (mGluR5+/+) mice, we showed induced PKCbeta2 or PKCgamma expression at the border between the stratum oriens and alveus (O/A border) at 2h during pilocarpine induced status epilepticus (SE), and in the stratum pyramidale in CA1 area at 1 day after pilocarpine induced SE; at 1 day, induced expression of PLCbeta4 in the stratum pyramidale of CA1 area was observed. Furthermore, double labeling revealed the co-localization of induced PKCbeta2 or PKCgamma with mGluR5 or with induced PLCbeta4 in the stratum pyramidale of CA1 area. These induced expression, however, were not found in mGluR5 mutant (mGluR5-/-) mice. It suggests that induced PLCbeta4-PKCbeta2/PKCgamma at 1 day after pilocarpine induced SE in pyramidal neurons or PKCbeta2 or PKCgamma in interneurons at O/A border at 2h during pilocarpine induced SE may be specifically linked to the activation of mGluR5. When compared to mGluR5+/+ mice, significant shorter latency (from pilocarpine injection to the occurrence of status epilepticus) and maintenance period (from beginning to the end of status epilepticus) for status epilepticus in mGluR5-/- mice were also demonstrated. It is possible that mGluR5 may play a negative role in initiation of status epilepticus by interacting with muscarinic acetylcholine receptor in mGluR5+/+ mice.
authors.affiliation: Epilepsy Research Laboratory, National Neuroscience Institute, Singapore, Singapore.
authors.forename: Jian Xin
authors.initials: JX
authors.lastname: Liu
authors.forename: Yong Cheng
authors.initials: YC
authors.lastname: Tang
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Feng Ru
authors.initials: FR
authors.lastname: Tang
mesh_terms: D000818:Animals; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000633:toxicity; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D054799:Phospholipase C beta / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D010862:Pilocarpine / Q000008:administration & dosage / Q000633:toxicity; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D064546:Protein Kinase C beta; D017966:Pyramidal Cells / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors; D000099221:Protein Kinase C zeta
chemical_list: D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins; D054799:Phospholipase C beta; D010862:Pilocarpine; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D000099221:Protein Kinase C zeta; C578936:Grm5 protein, mouse; C087857:protein kinase C gamma; C518043:Plcb4 protein, mouse