title: Persistent defect in transmitter release and synapsin phosphorylation in cerebral cortex after transient moderate ischemic injury.
abstract: 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.
authors: Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors: Hayrunnisa
authors: H
authors: Bolay
authors: Yasemin
authors: Y
authors: Gürsoy-Ozdemir
authors: Yildirim
authors: Y
authors: Sara
authors: Rüstü
authors: R
authors: Onur
authors: Alp
authors: A
authors: Can
authors: Turgay
authors: T
authors: Dalkara
mesh_terms: 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
chemical_list: 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