Effects Of ADAM10Deletion On CaMKⅡα Gene Expression, Glial Cell Proliferation And Synaptic Plasticity

Purpose: ADAM10is a member of the ADAM family. ADAM10plays a centralrole in the developing brain. ADAM10knock-out mice die at embryonic day9.5(E9.5) due to major developmental defects.This early lethality has precluded furtherinvestigation of ADAM10function in the brain in vivo[1]. For this reason, wegenerated the adult neuron-specific ADAM10gene knock mice to explore the impactof ADAM10deletion on the CaMKⅡαexpression, glial cell proliferation andsynaptic plasticity.Methods: Mice were identified by PCR genotyping. The levels of CaMKⅡα andGFAP mRNA and protein in the brain were detected by RT-PCR and Western blot,respectively. Nissl staining was used to observe the morphological structure of thebrain and to calculate the neuronal numbers. The proliferation of glial cells wasobserved by immunofluorescence staining. Long-term potentiation(LTP) wasrecorded for the synaptic plasticity.Results: The CaMKⅡα and GFAP mRNA levels were obviously elevated (n=3, P<0.01) and the levels of the CaMKⅡα and GFAP protein were significantly increasedin the ADAM10cKO mice compared with controls (n=5, P<0.01). In addition, theGFAP-positive cells were significantly increased in the ADAM10cKO mice. Nisslstaining showed that there was neuronal loss in the cerebral cortex and hippocampusof the ADAM10cKO mice. LTP test demonstrated that the synaptic plasticity isimpaired in the ADAM10cKO mouse hippocampus.Conclusion: ADAM10deletion leads to elevated levels of the GFAP and CaMKⅡα mRNAand protein in the brain, increase of glial cell numbers in the cortex andhippocampus, inflammation, neuronal loss, impaired synaptic plasticity and abnormalneuronal function.