Changes of PLCγ1/IP3R/CaMKⅡ protein expression and dendritic spine density in hippocampus of VPA-induced autistic young mice

Abstract

Objective To investigate expression changes of phospholipase C-γ1 (PLCγ1)/inositol triphosphate receptor (IP3R)/calmodulin-dependent kinase Ⅱ (CaMKⅡ) and density of dendritic spine in the hippocampus of autism model mice induced by sodium valproate (VPA). Methods Pregnant C57 mouse was given intraperitoneal injection of 300 mg/kg VPA or same volume of normal saline at the 10th and 12th days of gestation. The offspring exposed to VPA or saline during gestation were identified as autism spectrum disorder mice (VPA group) or normal control mice (CON group). Western blotting was used to detect the expression levels of PLCγ1, IP3R, CaMKⅡ and post-synaptic dense-95 (PSD95) in the hippocampus of the 2 groups. Golgi staining was employed to observe the changes in dendritic spines in the hippocampus of the offspring mice. Results Western blotting showed that the expression levels of PLCγ1, IP3R, CaMKⅡ and PSD95 were decreased in the VPA group than the normal control group (P < 0.01). Golgi staining indicated that compared with the normal control group, the density of dendritic spines in the hippocampus of VPA mice was reduced (P < 0.01). Conclusion In the hippocampus of VPA induced autism mice, the expression of PLCγ1/IP3R/CaMKⅡ and PSD95 and the dendritic spine density of pyramidal neurons in hippocampal CA1 are all decreased compared with the normal control mice.

Keywords

• autism spectrum disorder
• sodium valproate
• hippocampus
• phospholipase c-gamma1
• 1
• 4
• 5-trisphosphate receptor
• calmodulin-dependent protein kinase ⅱ
• dendritic spines
• postsynaptic density-95