Effect of Vitamin B12 combined with mouse nerve growth factor on intelligence improvement in rats with cerebral palsy and the related mechanism

Abstract

Objective To investigate the effect of vitamin B12 (VB12) combined with mouse nerve growth factor (MNGF) on the intelligence improvement in rats with cerebral palsy rats and the related mechanism. Methods Sixty 14-day-old Wistar rats were randomly divided into 5 groups: control group, model group, VB12 group, MNGF group and VB12+MNGF group (n=12 each) . Cerebral palsy was modeled in all rats except for the control group. The VB12 group was given intraperitoneal injection of 10 ml/kg VB12 (added with sterile normal saline to a final concentration of 70 mg/100 ml) once daily; the MNGF group was given intraperitoneal injection of 0.2 ml MNGF once daily; the VB12+MNGF group received combined intervention as in the VB12 group and the MNGF group; the control group and the model group were given the equivalent amount of sterile normal saline. All the young rats were intervened for 21 days, and were then compared for the general conditions, results of Y-maze test, cerebral cortex apoptosis index (AI) , and the mRNA and protein expression of aspartate-specific cysteine protease-3 (Caspase-3) , B cell lymphoma/leukemia-2 (Bcl-2) , Bcl-2 related X protein (Bax) in the prefrontal cortex brain tissues. Results The control group were normal in dieting, rotation behaviors, walking, daily activities, sleep, urination and defecation. The body weight showed a tendency of natural growth in all groups, which was most eminent in the control group, followed by VB12+MNGF group, MNGF group, VB12 group, and the model group. The number of correct response and the time spent running to the safety zone with light on in the Y maze test, cerebral cortex AI, and the mRNA and protein expression of Caspase-3, Bcl-2 and Bax in the prefrontal cortex brain tissues statistically significant among groups (P<0.05) and between groups (P<0.05) . The control group showed the highest number of correct response, followed by the VB12+MNGF group, MNGF group, VB12 group and model group. The model group had the longest time to escape to the safety zone with light on, followed by the VB12 group, MNGF group, VB12+MNGF group, and the control group. The levels of cerebral cortex AI, and the mRNA and protein expression of Caspase-3 and Bax in the prefrontal cortex brain tissues were the highest in the model group, followed by VB12 group, MNGF group, VB12+MNGF group and the control group. The levels of Bcl-2 mRNA and protein expression were the highest in the control group, followed by VB12+MNGF group, MNGF group, VB12 group and model group. Conclusion VB12 combined with MNGF may significantly improve the general condition and intelligence, and reduce neuronal apoptosis in the cerebral cortex of young rats with cerebral palsy, probably via down-regulating the mRNA and protein expression of Caspase-3 and Bax mRNA and protein, and up-regulating the mRNA and protein expression of Bcl-2. Key words: Vitamin B12; Mouse nerve growth factor; Cerebral palsy; Young rats; Intelligence; Mechanism