Shuyuan Yang

The Wnt /β-catenin signaling pathway in the adult neurogenesis

The Wnt/β‐catenin signaling pathway plays an important role in neural development, β‐catenin is a central component of the Wnt/β‐catenin signaling pathway, which not only performs the function of transmitting information in the cytoplasm, but also translocates to the nucleus‐activating target gene transcription. The target genes in neural tissues have not been fully revealed, but the effects of the Wnt/β‐catenin signaling pathway in adult neurogenesis have been demonstrated by ongoing research, which are significative to the basic research and treatment of neuronal degeneration diseases. Here, we review key findings to show the characteristics of β‐catenin and its pivotal nature in the Wnt/β‐catenin signaling pathway in a number of molecular studies. We also review current literature on the role of β‐catenin in adult neurogenesis, which consists of an active process encompassing the proliferation, migration, differentiation and final synaptogenesis.

Hes1, a Notch signaling downstream target, regulates adult hippocampal neurogenesis following traumatic brain injury.

Hairy and enhancer of split 1 (Hes1), a downstream target of Notch signaling, has long been recognized as crucial in inhibiting neuronal differentiation. However, the role of Hes1 following traumatic brain injury (TBI) in adult neurogenesis in the mouse dentate gyrus (DG) remains partially understood. Here, we investigate the role of Hes1 in regulating neurogenesis in the DG of the adult hippocampus after TBI by up- or downregulating Hes1 expression. First, adenovirus-mediated gene transfection was employed to upregulate Hes1 in vivo. The mice were then subjected to TBI, and the hippocampal tissue was collected for Western blot analysis at designated times, pre- and post-injury. Moreover, the brain slices were stained for BrdU and doublecortin (DCX). We show that enhancing Hes1 inhibits the proliferation and differentiation of neural precursor cells (NPCs) in the DG of the hippocampus soon after TBI. Second, downregulation of Hes1 via RNA interference (RNAi) results in a significant increase in neuronal production and promotes the differentiation of NPCs into mature neurons in the DG, as assessed by BrdU and NeuN double staining. Furthermore, a Morris water maze (MWM) test clearly confirmed that the knockdown of Hes1 improves the spatial learning and memory capacity of adult mice following injury. Taken together, these observations suggest that Hes1 represents a negative regulator of adult neurogenesis post-TBI and that the precise space-time regulation of Hes1 expression in the DG may promote the recovery of neural function following TBI.

Survivin, a key component of the Wnt/β‑catenin signaling pathway, contributes to traumatic brain injury-induced adult neurogenesis in the mouse dentate gyrus

The enhancement of endogenous neurogenesis has been suggested in the treatment of traumatic brain injury (TBI); however, the factors that trigger the process of adult neurogenesis following TBI remain elusive. In the adult mammalian central nervous system, there are 2 neurogenic regions: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles, both of which maintain relatively quiescent states in a stable microenvironment. However, once stimulated by intrinsic and extrinsic events, relevant signals are activated in these 2 regions. In this study, in order to explore the mechanisms behind endogenous neurogenesis following TBI, we investigated potential factors regulating this process. We observed that the expression of survivin, an anti-apoptotic protein, increased in a time-dependent manner in the hippocampus in a mouse model of TBI. In addition, the number of survivin (+) cells, as well as that of BrdU (+) cells increased in the SGZ of the dentate gyrus (DG) in the hippocampus following TBI, as shown by immunofluorescence double staining; the co-localization of survivin and BrdU was shown in the merged images. The expression of survivin was also significantly increased in the doublecortin (DCX) (+) immature neurons in the DG of the hippocampus soon after the induction of TBI. Taken together, these data confirm the connection between the expression of survivin and adult neurogenesis following TBI; our data also suggest the therapeutic potential of upregulating survivin expression as a novel strategy for the effective treatment of TBI.

A new finding concerning adenoviral-mediated gene transfer: a high-level, cell-specific transgene expression in the neural stem cells of adult mice.

Adenoviruses are highly efficient vectors for gene transfer into brain cells. Restricting transgene expression to specific cell types and maintaining long-term expression are major goals for adenoviral-mediated gene transfer in the central nervous system. Human adenovirus type 5 (Ad5) mediated transgene expression is described under the control of the murine cytomegalovirus (mCMV) immediate-early promoter. It was found that the neural stem cells in the dentate subgranular zone were transduced preferentially, minimal neurons were transduced in the granule cell layer of the dentate gyrus, no EGFP was detected in the pyramidal cell layers of CAl to CA3 area and EGFP activity can be detected for 2 months after infection. Therefore, the mCMV-adenoviral vectors can be used both for studying the function of various genes in the differentiation of neural stem cells and, ultimately, for gene therapy or to modulate specific gene expression.

CTA Characteristics of the Circle of Willis and Intracranial Aneurysm in a Chinese Crowd with Family History of Stroke

Background and Purpose. The vascular morphology in crowd with family history of stroke remains unclear. The present study clarified the characteristics of the intracranial vascular CoW and prevalence of intracranial aneurysms in subjects with family history of stroke. Methods. A stratified cluster, random sampling method was used for subjects with family history of stroke among rural residents in Jixian, Tianjin, China. All the subjects underwent a physical examination, head computed tomography (CT) scan, and cephalic and cervical computed tomography angiography (CTA) scan. Anatomic variations in the Circle of Willis and cerebrovascular disease in this population were analyzed. Results. In the crowd with similar living environment, stable genetic background, and family history of stroke and without obvious nerve function impairment (1) hypoplasia or absence of A1 segment was significantly different in gender (male versus female: 9.8% versus 18.8%, p = 0.031), especially the right-side A1 (male versus female: 5.9% versus 16.4%, p = 0.004). (2) Hypoplasia or absence of bilateral posterior communicating arteries was more common in men than women (58.2% versus 45.3%, p = 0.032). Unilateral fetal posterior cerebral artery was observed more often in women than men (17.2% versus 8.5%, p = 0.028). (3) The percentage of subjects with incomplete CoW did not increase significantly with age. Compared to healthy Chinese people, the crowd had a higher percentage of incomplete CoW (p < 0.001). (4) No obvious correlation between risk factors and CoW was found. (5) The prevalence of aneurysm was 10.3% in the special crowd. Conclusions. The certain variations of CoW showed significant relation to gender, but not to age in people with family history of stroke. The incomplete circle may be a dangerous factor that is independent of common risk factors for stroke and tend to lead to cerebral ischemia in the crowd with family history of stroke. The prevalence of intracranial aneurysm is comparatively high in the present subjects compared to other people.