CRMP2 improves memory deficits by enhancing the maturation of neuronal dendritic spines after traumatic brain injury

• Published in: Experimental neurology 2020-06, Vol.328, p.113253-113253, Article 113253
• Main Authors: Sun, Yi-Yu, Zhu, Liang, Sun, Zhao-Liang, Feng, Dong-Fu
• Format: Article
• Language: English
• Subjects: Animals; Brain Injuries, Traumatic - complications; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - pathology; CRMP2; Dendritic spine; Dendritic Spines - metabolism; Hippocampus - metabolism; Hippocampus - pathology; Intercellular Signaling Peptides and Proteins - metabolism; Learn and memory function; Memory Disorders - etiology; Memory Disorders - metabolism; Mice; Nerve Tissue Proteins - metabolism; Recovery of Function - physiology; Traumatic brain injury
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2020.113253

Our recent study investigated the role of collapsin response mediator protein-2 (CRMP2) on dendritic spine morphology and memory function after traumatic brain injury (TBI). First, we examined the density and morphology of dendritic spines in Thy1-GFP mice on the 1 st day (P1D) and 7th day (P7D) after controlled cortical impact injury (CCI). The dendritic spine density in the hippocampus was decreased on P1D, in which mainly mushroom-type and thin-type spines were lost. The density of dendritic spines was increased on P7D, most of which were of the thin type. Next, we explored the expression of CRMP2 on P1D and P7D. CRMP2 expression was decreased on P1D, but the levels of the CRMP2 breakdown product were increased. On P7D, the expression pattern was the opposite. Then, we constructed CRMP2 overexpression and knockdown plasmids and transfected them into cultured neurons in vitro. CRMP2 increased the dendritic spine density of cultured neurons and the proportion of mushroom-type spines, while CRMP2-shRNA reduced the dendritic spine density and the proportion of mushroom-type spines. To determine the role of CRMP2 in dendritic spines after TBI, we stereotactically injected the CRMP2 overexpression and knockdown viruses into the hippocampus and found that CRMP2 increased the dendritic spine density and the proportion of mushroom-type spines after TBI. Meanwhile, as suggested by the morphological changes, fear conditioning behavioral experiments confirmed that CRMP2 improved memory deficits after TBI. •Reveal the changing relationship between CRMP2 expression and the morphology of spines.•CRMP2 increases spine density and promotes recovery of mushroom type spines after TBI.•CRMP2 improved memory deficit after TBI.