Long-term increase in protein kinase C-gamma and muscarinic acetylcholine receptor expression in the cerebral cortex of amygdala-kindled rats--a quantitative immunocytochemical study.
Kindling is an animal model for epilepsy in which repeated application of an electrical stimulus to brain pathways results in an epileptic focus. The animal holds a permanent state of hyperexcitability to the stimulus for the rest of its life. Understanding the cellular and molecular processes underlying hyperexcitability could provide insight into epileptogenesis. Furthermore, it could elucidate cellular and molecular bases of synaptic plasticity in the central nervous system. In the present study the long-term effect of a kindled focus in the amygdala on the gamma-isoform of protein kinase C and the muscarinic cholinergic receptor as cellular messengers was evaluated in the cerebral cortex of rats. Following an average of 10 bilaterally generalized seizures kindling stimulation was terminated and rats were left undisturbed for approximately three months. Brains were processed by immunocytochemistry using monoclonal antibodies against protein kinase C-gamma and muscarinic cholinergic receptor protein. Digital image analysis of sections through the entire forebrain revealed an increase in optical density of both protein kinase C-gamma and the muscarinic cholinergic receptor in the piriform and entorhinal cortex of the hemisphere contralateral to the stimulation site in kindled rats. However, on the ipsilateral side no change was observed in comparison with electrode implanted nonkindled control rats. The observed increase in expression of muscarinic cholinergic receptor protein and a component of the phosphoinositide second messenger system (protein kinase C-gamma) located in specific areas of the cerebral cortex in kindled rats could serve as a basis for the permanent state of hyperexcitability in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Beldhuis
H J
HJ
Department of Animal Physiology, University of Groningen, Haren, The Netherlands.
De Ruiter
A J
AJ
Maes
F W
FW
Suzuki
T
T
Bohus
B
B
D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D007091:Image Processing, Computer-Assisted; D007696:Kindling, Neurologic; D008297:Male; D008563:Membrane Lipids / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology; D011493:Protein Kinase C / Q000096:biosynthesis*; D051381:Rats; D011976:Receptors, Muscarinic / Q000096:biosynthesis*; D015290:Second Messenger Systems; D009435:Synaptic Transmission
D008563:Membrane Lipids; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D011493:Protein Kinase C