Proliferated Capability Of Neural Stem Cell In The Discrete Brain Region Is Associated With The Insulin/ILPs Signaling During Aging

Plastic ability of brain partly associates the state of neural stem cells origenated from the discrete the brain region throughout life, particularly, involving in repair process after brain injury. Among the veriaty of regulated factors, age is a critical factor in determination of neural stem cells fate. The key factors are the age, changes of metabolic in brain caused by aging is complex and three-dimensional. Although it is still unable to determine which is the most important factor in aging that affects neural stem cell function, some studies show that with aging, the insulin/insulin-like polypeptide signal decreased in brain, while the insulin/insulin-like polypeptide plays a key role in embryonic development. However the relationship between stem cell state and the insulin signal changes in adult brain remains unclear. The present study aims to investigate relationship between the change of proliferation of adult stem cells in the process of aging in subventricular zone (subventricular zone, SVZ) and changes of insulin-like peptide (ILPs) in brain.Methods:C57B/L mice were bred to2months,12months,18months before executed, the Morris water maze was used to investigate the spatial memory ability before death, detecting the difference of serum biochemical in young and old group. All animals were sacrificed before intraperitoneal injection of BrdU (60mg/kg,3days before the execution of the start of injection, continuous injection3days,1time/day). Part of the animal were executed, prefrontal cortex was isolated and stored in ice and frozen in-80℃, other animals were perfused for fixation, coronal frozen sections alternate. We evaluated of prefrontal cortex pyramidal cells density by CV staining combined with three-dimensional count. Cells in SVZ were observed by using Fluoro Jada C technology, and expression level of BrdU and Ki67in SVZ was detected by immunohistochemistry. Expression level of β-Catenin and p-GSK3βin the prefrontal cortex of mice were tested by Western blot technology and the the level of transcription of insulin,1GF-1, IGF1receptor in hippocampal by PCR assay.Results:The spatial memory capacity in18months mice were lower than in2months group. But the level of serum insulin in18months mice were higher than in2months group. The density of vertebral cell decreased with aging the number of BrdU and Ki67positive cells in SVZ of18months group obviously decreased than2months group(P<0.05). The results of Western blot showed that the expression level of β-Catenin in forehead cortex were most in the2months group, whereas in12and18months group were decreased gradually; p-GSK3beta expression were most in12months group while in18months group was gradually reduced The results of PCR showed that the transcription level of insulin and IGF1receptor in hippocampal were most in2months group, while in12months and18months group were significantly decreased; the transcription level of IGF1were in12months group, whereas in18months was significantly decreased.Conclusion:The results showed that the proliferation ability of the SVZ cells decreased gradually with aging was possibly due to the decline of central insulin-like peptide signals.