Persistent defect in transmitter release and synapsin phosphorylation in cerebral cortex after transient moderate ischemic injury.
OBJECTIVE
Synaptic transmission is highly vulnerable to metabolic perturbations. However, the long-term consequences of transient metabolic perturbations on synapses are not clear. We studied the long-lasting changes in synaptic transmission and phosphorylation of presynaptic proteins in penumbral cortical neurons after transient moderate ischemia.


METHODS
Rats were subjected to 1 hour of middle cerebral artery occlusion. After reperfusion, electric activity of neurons in the peri-infarct region was recorded intracellularly and extracellularly in situ. Phosphorylation of synapsin-I and tyrosine residues was studied by immunohistochemistry.


RESULTS
Neurons in the penumbra displayed no postsynaptic potentials 1 to 3 hours after recirculation. However, these cells were able to generate action potentials and were responsive to glutamate, suggesting that postsynaptic excitability was preserved but the synaptic transmission was blocked because of a presynaptic defect. The synaptic transmission was still depressed 24 hours after recirculation in neurons in the peri-infarct area that survived ischemia. The amount of immunoreactive synapsin-I, synaptophysin, and synaptotagmin was not appreciably changed for 72 hours after reperfusion. However, phosphorylation of synapsin-l was significantly decreased, whereas phosphotyrosine immunoreactivity was increased, suggesting a selective defect in synapsin-I phosphorylation.


CONCLUSIONS
These data demonstrate that synaptic transmission may be permanently impaired after transient moderate brain injury. Since postsynaptic excitability is preserved, the transmission failure is likely to be caused by presynaptic mechanisms, one of which may be impaired phosphorylation of presynaptic proteins.
Bolay
Hayrunnisa
H
Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Gürsoy-Ozdemir
Yasemin
Y
Sara
Yildirim
Y
Onur
Rüstü
R
Can
Alp
A
Dalkara
Turgay
T
D000818:Animals; D002135:Calcium-Binding Proteins; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018450:Disease Progression; D018698:Glutamic Acid / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016704:Synapsins / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D050857:Synaptotagmins; D013995:Time
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D016704:Synapsins; D016708:Synaptophysin; D050857:Synaptotagmins; D019000:Phosphotyrosine; D018698:Glutamic Acid