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21.
Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis 下载免费PDF全文
Shu‐Na Wang Tian‐Ying Xu Wen‐Lin Li Chao‐Yu Miao 《CNS Neuroscience & Therapeutics》2016,22(6):431-439
Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate‐limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT‐mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self‐renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration. 相似文献
22.
Xian-Jun Wang Xiao-Jie Song Pei-Hong Gao Xue-Ying Zhou 《The International journal of neuroscience》2016,126(2):154-162
Aim and Methods: Estradiol (E2) is reported to attenuate β-amyloid (Aβ) accumulation and slow the progression of Alzheimer's disease (AD). This study explored the beneficial effect of E2 in AD using histological examination and electrophysiological recording technique in AD model mice created by intracerebroventricular injection of β-amyloid 25–35 (Aβ25–35). Results: Infusion of Aβ25–35 reduced the number of newborn neurons in the 2nd week after birth, a critical period for neurite growth, and impaired high-frequency stimulation-dependent long-term potentiation (LTP) induction in perforant path-granular synapses of hippocampal dentate gyrus (DG). Administration of E2 from the 2nd to 4th week after cell birth in Aβ25–35-mice ameliorated the impairment of newborn neurons and LTP induction in DG. Acute application of E2 failed to increase the newborn neurons and rescue LTP induction in the DG of Aβ25–35-mice. Conclusions: The effect of E2 in Aβ25–35-impaired LTP induction depends on its neuroprotection improvement. 相似文献
23.
Li Ling Zhangge Ji Huihong Huang Gang Yao Muzhen Wang 《The International journal of neuroscience》2016,126(5):469-477
Previous studies have demonstrated that prostaglandin E1 (PGE1) has a neuroprotective effect on cerebral ischemia. However, it remains unknown whether PGE1 promotes angiogenesis and neurogenesis after ischemic stroke. In this study, adult male Sprague-Dawley rats were subjected to permanently distal middle cerebral artery occlusion (MCAO). Rats were treated with lipo-prostaglandin E1(lipo-PGE1, 10 μg/kg/d) or the same volume of 0.9% saline starting 24 hours after MCAO daily for 6 consecutive days. All rats were injected 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg) intraperitoneally every 12 hours for 3 consecutive days before being sacrificed. At 7 and 14 days after MCAO or sham-operation, rats were sacrificed. Post-stroke neurological outcome, infarction volume, angiogenesis and neurogenesis were evaluated. Treatment with lipo-PGE1 significantly increased the vascular density in the peri-infarct areas at 7 and 14 days after MCAO. The lipo-PGE1 treatment significantly enhanced the proliferation and migration of endogenous neural stem cells in the ipsilateral subventricular zone. The neural stem cells associated with blood vessels closely within a neurovascular niche in lipo-PGE1-treated rats after stroke. The lipo-PGE1 treatment also significantly improved the neurological recovery after MCAO. These results indicate that treatment with lipo-PGE1 promotes post-stroke angiogenesis, neurogenesis and their interaction, which would contribute to neurological recovery after cerebral infarction. Our study provides novel experimental evidences for the neuroprotective roles of PGE1 in ischemic stroke. 相似文献
24.
Integrins are transmembrane receptors that mediate cell‐extracellular matrix and cell–cell interactions. The β1‐integrin subunit is highly expressed by embryonic neural stem cells (NSCs) and is critical for NSC maintenance in the developing nervous system, but its role in the adult hippocampal niche remains unexplored. We show that β1‐integrin expression in the adult mouse dentate gyrus (DG) is localized to radial NSCs and early progenitors, but is lost in more mature progeny. Although NSCs in the hippocampal subgranular zone (SGZ) normally only infrequently differentiate into astrocytes, deletion of β1‐integrin significantly enhanced astrocyte differentiation. Ablation of β1‐integrin also led to reduced neurogenesis as well as depletion of the radial NSC population. Activation of integrin‐linked kinase (ILK) in cultured adult NSCs from β1‐integrin knockout mice reduced astrocyte differentiation, suggesting that at least some of the inhibitory effects of β1‐integrin on astrocytic differentiation are mediated through ILK. In addition, β1‐integrin conditional knockout also resulted in extensive cellular disorganization of the SGZ as well as non‐neurogenic regions of the DG. The effects of β1‐integrin ablation on DG structure and astrogliogenesis show sex‐specific differences, with the effects following a substantially slower time‐course in males. β1‐integrin thus plays a dual role in maintaining the adult hippocampal NSC population by supporting the structural integrity of the NSC niche and by inhibiting astrocytic lineage commitment. GLIA 2016;64:1235–1251 相似文献
25.
Psychosocial stress, and within the neuroendocrine reaction to stress specifically the glucocorticoid hormones, are well-characterized inhibitors of neural stem/progenitor cell proliferation in the adult hippocampus, resulting in a marked reduction in the production of new neurons in this brain area relevant for learning and memory. However, the mechanisms by which stress, and particularly glucocorticoids, inhibit neural stem/progenitor cell proliferation remain unclear and under debate.Here we review the literature on the topic and discuss the evidence for direct and indirect effects of glucocorticoids on neural stem/progenitor cell proliferation and adult neurogenesis. Further, we discuss the hypothesis that glucocorticoid rhythmicity and oscillations originating from the activity of the hypothalamus-pituitary-adrenal axis, may be crucial for the regulation of neural stem/progenitor cells in the hippocampus, as well as the implications of this hypothesis for pathophysiological conditions in which glucocorticoid oscillations are affected. 相似文献
26.
肢体远隔缺血期适应联合后适应促进大鼠缺血性脑卒中模型神经发生的作用及机制 《首都医科大学学报》2023,44(1):54-61
目的 探讨肢体远隔缺血期适应(per-conditioning,PerC)联合后适应(post-conditioning,PostC)对缺血性脑卒中后神经再生的作用,并明确PerC联合PostC对脂肪酸β-氧化(fatty acid β-oxidation,FAO)限速酶——肉毒碱棕榈酰转移酶(carnitine palmitoyl transferase 1A,CPT1A)的影响。方法 对成年雄性SD大鼠进行大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)造模,MCAO模型后30 min进行肢体远隔缺血期适应治疗(PerC),再灌注24 h后重复进行肢体远隔缺血适应(PostC),1次/d,直到取材。再灌注14 d后对大鼠进行神经功能评分,通过免疫组织化学染色检测室管膜下区(subependymal ventricular zone, SVZ)神经再生情况,通过酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测CPT1A的表达。结果 与MCAO组及PerC/PostC组比较,PerC+PostC组大鼠,身体不对称运动行为评分降低,神经干细胞的数量以及向梗死区迁移的细胞数量增加。Pearson相关性分析显示,神经干细胞的数量与神经功能呈负相关(r=-0.917 9, P<0.0001)。然而,迁移到基底节区的神经干细胞的凋亡数量在各组之间差异无统计学意义。机制研究显示,PerC+PostC组CPT1A的蛋白水平显著增加。结论 PerC联合PostC治疗能够通过增加神经干细胞的数量改善神经功能,神经干细胞的脂肪酸氧化可能是其促进神经干细胞迁移的机制之一。 相似文献
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28.
Sashrika Pillay Adhil Bhagwandin Mads F. Bertelsen Nina Patzke Gerhard Engler Andreas K. Engel Paul R. Manger 《The Journal of comparative neurology》2021,529(1):8-27
Employing cyto‐, myelo‐, and chemoarchitectural staining techniques, we analyzed the structure of the hippocampal formation in the banded mongoose and domestic ferret, species belonging to the two carnivoran superfamilies, which have had independent evolutionary trajectories for the past 55 million years. Our observations indicate that, despite the time since sharing a last common ancestor, these species show extensive similarities. The four major portions of the hippocampal formation (cornu Ammonis, dentate gyrus, subicular complex, and entorhinal cortex) were readily observed, contained the same internal subdivisions, and maintained the topological relationships of these subdivisions that could be considered typically mammalian. In addition, adult hippocampal neurogenesis was observed in both species, occurring at a rate similar to that observed in other mammals. Despite the overall similarities, several differences to each other, and to other mammalian species, were observed. We could not find evidence for the presence of the CA2 and CA4 fields of the cornu Ammonis region. In the banded mongoose the dentate gyrus appears to be comprised of up to seven lamina, through the sublamination of the molecular and granule cell layers, which is not observed in the domestic ferret. In addition, numerous subtle variations in chemoarchitecture between the two species were observed. These differences may contribute to an overall variation in the functionality of the hippocampal formation between the species, and in comparison to other mammalian species. These similarities and variations are important to understanding to what extent phylogenetic affinities and constraints affect potential adaptive evolutionary plasticity of the hippocampal formation. 相似文献
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30.
生长激素的生理作用主要是促进物质代谢与生长发育。研究表明,生长激素对机体各器官和各组织均有影响,在神经系统疾病的神经再生和神经保护过程中,生长激素也起到了一定的作用。本文总结生长激素治疗常见神经系统疾时所起的作用以及可能的机制。 相似文献