CPG15,A New Factor Upregulated after Ischemic Brain Injury,Contributes to Neuronal Network Re-Establishment after Glutamate-Induced Injury

Candidate plasticity-related gene 15 (cpg15) encodes a protein that regulates dendritic and axonal arbor growth and synaptic maturation. In the present study, we investigated the potential role of CPG15 in regulating the neuronal network re-establishment after ischemic brain injury. In the mouse model with transient global ischemia (TGI), CPG15 transcripts and proteins were determined using RT-PCR and Western blot analyses. Cell proliferation was observed using 5′-bromo-2′-deoxyuridine-5′-monophosphate (BrdU) labeling. Double immunostaining and depletion of soluble CPG15 proteins were performed to examine the cellular distribution of CPG15 and the role of soluble CPG15 in the neurite outgrowth during the neuronal network re-establishment in primarily cultured hippocampal cells after glutamate-induced injury. We demonstrated that CPG15 expression in the hippocampus was upregulated at 1–2 weeks after TGI. In the dentate gyrus, the number of CPG15 and BrdU positive cells increased concurrently after the injury. During the neuronal network re-establishment after the glutamate-induced injury of primarily cultured hippocampal cells, CPG15 was mainly located at the ends and turn-off regions of the growth cones and in the vesicles. Depletion of soluble CPG15 proteins secreted from the hippocampal cells in the culture media significantly reduced the neurite outgrowth and neuron-neuron connection. The results indicate that CPG15 may function as a new factor required in re-establishment of neuronal network after the injury. Our findings will be important in developing a new strategy to enhance endogenous neurogenesis after an ischemic brain injury.