1. Postischemic PKC activation rescues retrograde and anterograde long-term memory
- Author
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Miao-Kun Sun, Daniel L. Alkon, and Jarin Hongpaisan
- Subjects
Male ,Dendritic spine ,Time Factors ,Dendritic Spines ,Ischemia ,Synaptogenesis ,Enzyme Activators ,Apoptosis ,Motor Activity ,Hippocampus ,Brain Ischemia ,Brain ischemia ,Memory ,medicine ,In Situ Nick-End Labeling ,Animals ,Rats, Wistar ,Hypoxia ,Maze Learning ,Protein kinase C ,Protein Kinase C ,Multidisciplinary ,biology ,Long-term memory ,Hypoxia (medical) ,Biological Sciences ,medicine.disease ,Bryostatins ,Rats ,Enzyme Activation ,Microscopy, Electron ,biology.protein ,Synaptic Vesicles ,medicine.symptom ,Neuroscience ,Neurotrophin - Abstract
Therapeutics for cerebral ischemia/hypoxia, which often results in ischemic stroke in humans, are a global unmet medical need. Here, we report that bryostatin-1, a highly potent protein kinase C (PKC) activator, interrupts pathophysiological molecular cascades and apoptosis triggered by cerebral ischemia/hypoxia, enhances neurotrophic activity, and induces synaptogenesis in rats. This postischemic therapeutic approach is further shown to preserve learning and memory capacity even 4 months later as well as long-term memory induced before the ischemic event. Our results of electromicroscopic and immunohistochemical analyses of neuronal and synaptic ultra-structure are consistent with a PKC-mediated synaptic remodeling and repair process that confers long-lasting preservation of spatial learning and memory before and after the cerebral ischemic/hypoxic event, suggesting a previously undescribed therapeutic modality for cerebral ischemia/hypoxia and ischemic stroke.
- Published
- 2009