Neurogenesis Research Articles (Page 2)

Objective To evaluate the effects of sevoflurane on hippocampal neurogenesis in dentate gyrus (DG) of mice of different ages. Methods Ninety-six SPF healthy male C57BL/6 mice, aged 2 weeks, 6 weeks, 9 months and 20 months (24 mice for each age, 12 mice for each group), were divided into 2 groups (n=48 each) using a random number table method: control group (group C) and sevoflurane group (group S). Group S inhaled 3.0% sevoflurane for 2 h once a day for 3 consecutive days, while group C inhaled the mixture of air and O2.Six mice of each age were selected, and 5′-bromo-2′-deoxyuridine (BrdU) 50 mg/kg was intraperitoneally injected immediately before and after inhalation once a day for 3 consecutive days in two groups.Mice were sacrificed at 24 h after the last inhalation (T1), brains were removed and hippocampi isolated for determination of the number of nestin and doublecortin (DCX) positive cells in DG by immunohistochemistry.Mice were sacrificed at 4 weeks after the last inhalation (T2), brains were removed and hippocampi isolated for determination of the number of neuronal nuclei antigen (NeuN)/BrdU and glial fibrillary acid protein (GFAP)/BrdU positive cells by immunofluorescence. Results Compared with group C, the number of nestin and DCX positive cells was significantly reduced at T1, and the number of NeuN/BrdU and GFAP/BrdU positive cells was reduced at T2 in mice of 2 weeks and 20 months old (P 0.05). Conclusion Three percent sevoflurane can inhibit hippocampal neurogenesis in DG of immature and old mice and exerts no influence on hippocampal neurogenesis in DG of juvenile and adult mice. Key words: Anesthetic, inhalation; Age; Neurogenesis; Hippocampus

Spinal cord injury (SCI) has remained a challenging area for scientists. In recent years, with the development and research of endogenous neural stem cells in the central nervous system, the use of endogenous neural stem cells (ENSCs) in the treatment of brain diseases has made some progress, but almost no activation of spinal cord ENSCs to repair spinal cord function recovery report. To identify the identity and distribution of ENSCs in the adult spinal cord, to analyze their fate mechanism, to find its active intervention target, has become a new idea for the treatment of spinal cord injury. Recent studies have shown that the ependymal cells of the spinal cord have the potential of neural stem cells, the current research progress is summarized. Key words: Ependymal cell; Spinal cord injury; Endogenous neural stem cell; Niche; Neurogenesis; Wound repair

Objective To investigate the influences of anterior thalamic nucleus (ANT) stimulation on neurogenesis in hippocampus of epileptic rats. Methods Thirty-two male SD rats were randomly allocated to normal-control group(n=8), control-stimulation group(n=8), sham-stimulation group(n=8) and model-stimulation group(n=8). Eqileptic SD rat model was established by using microinjection of kainic acid in hippocampal CA3 area, and administered 48 h continuous ANT stimulation in the chronic stage.Epileptic seizures were monitored and counted.The levels of Ki-67, a neurogenesis protein in hippocampus was determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Results The epilepsy seizure rate was (5.9±2.2) per week in the sham-stimulation group and (2.9±1.1) per week in model-stimulation group.Compared with sham-stimulated rats, ANT stimulation reduced seizures by 50.8% (P<0.05). Western blot analysis revealed that the relative levels of Ki-67 in the hippocampus of model-stimulation group significantly higher than that of the sham-stimulation group((0.44±0.15) vs (0.19±0.73), P<0.05). qRT-PCR analysis showed that relative levels of Ki-67 mRNA in the hippocampus of model-stimulation group were significantly higher than that of the sham-stimulation group((0.45±0.10) vs (0.15±0.06), P<0.05). Conclusion Chronic ANT stimulation can promote neurogenesis in epileptic rats, which may be a principle mechanism of the beneficial effect of ANT stimulation on epilepsy. Key words: Anterior thalamic nucleus; Electrical stimulation; Neurogenesis; Epilepsy

In a recent study of hippocampal neurogenesis across the lifespan, little evidence was found for new progenitor or mature neurons after age 7 in

Neurogénesis en cerebro adulto

Background Results of in vivo and in vitro animal studies have raised a significant concern that commonly used general anesthetics may induce neurotoxicity in the developing brain. Objective To make a review of the recent advances in pre-clinical studies that focused on the potential neurotoxicity of general anesthetics. Content Effects of anesthetics on apoptotic neuronal death, synapse formation and function, dendrite elaboration and axon guidance, and neurogenesis were identified as possible mechanisms of anesthetic-induced toxicity in the immature brain, which may cause long-term neurobehavioral deficits. Trend Making further improvement on understanding of general anesthetic induced neurotoxicity may provide potential therapeutic targets for the long-term cognitive deficits. Key words: Anesthetics, general; Immature brain; Neurotoxicity

The brain is an important organ that controls all sensory and motor actions, memory, and emotions. Each anatomical and physiological modulation in various brain centers, results in psychological, behavioral, and sensory-motor changes. Alcohol and addictive drugs such as opioids and amphetamines have been shown to exert a great impact on brain, specifically on the hippocampus. Emerging evidence has indicated that altered hippocampal neurogenesis is associated with the pathophysiology of neuropsychological disorders including addiction. The addictive drugs impair neurogenesis and undermine the function of neural stem/progenitor cells in hippocampus. This feature was claimed to be one of the underlying mechanisms of behavioral changes in patients with addiction. As the impairment of stem cells’ function has been proven to be the underlying cause of pathologic neuroadaptations in the brain, the administration of stem cell populations has shown promising results for re-modulating of neuronal status in the brain and especially in the hippocampus. Among the different types of stem cells, bone marrow derived mesenchymal stem cells are the most proper candidates for stem cell therapies. In this review article, the recent studies on the effects of addictive drugs on brain neurogenesis, and also the promising potential effects of stem cells in curing addiction related hippocampal damages are discussed.

Inhibition of Proliferation and Neurogenesis of Mouse Subventricular Zone Neural Stem Cells by a Mitochondrial Inhibitor Rotenone

Alzheimer's disease (AD) is a common cause of dementia. Alzheimer's disease (AD) is characterized by progressive loss of memory in addition to cortical atrophy. Despite decades of research and therapeutic trials in AD, an effective treatment is yet to be developed. Mesenchymal stem cells (MSCs) have emerged as promising tools for the treatment of AD, and clinical trials have been completed or are in progress. MSCs secrete various cytotropic factors that may exert beneficial effects in AD. The route of administration is an important factor to enhance MSC based treatment effects for AD. Among various routes, the intracerebroventricular route may possess several advantages such as the activation of neurogenesis, compared to other routes for AD treatments. In this review, we will focus on recent pre-clinical and clinical advances in MSC-based treatment of AD, specifically in relation to enhancement of endogenous neurogenesis.

Neural development is a complex process.Its development is affected by a variety of molecular signals such as signals from intestinal microorganisms.Recent animal research showed that microorganisms play an important role in neurogenesis, myelination, microglial cell maturation and formation of blood-brain barrier, and the regulation of animal behavior from many aspects.This article reviewed the impact of prenatal and postnatal gut microbes on the development and function of the nervous system, and the relationship between gut microbes and autism spectrum disorder as well. Key words: Intestinal microflora; Autism spectrum disorder; Neurogenesis

Natural and forced neurogenesis: similar and yet different?

Neuronal differentiation and cell-cycle exit are tightly coordinated, even in pathological situations. When pathological neurons re-enter the cell cycle and progress through the S phase, they undergo cell death instead of division. However, the mechanisms underlying mitotic resistance are mostly unknown. Here, we have found that acute inactivation of retinoblastoma (Rb) family proteins (Rb, p107 and p130) in mouse postmitotic neurons leads to cell death after S-phase progression. Checkpoint kinase 1 (Chk1) pathway activation during the S phase prevented the cell death, and allowed the division of cortical neurons that had undergone acute Rb family inactivation, oxygen-glucose deprivation (OGD) or in vivo hypoxia-ischemia. During neurogenesis, cortical neurons became protected from S-phase Chk1 pathway activation by the DNA methyltransferase Dnmt1, and underwent cell death after S-phase progression. Our results indicate that Chk1 pathway activation overrides mitotic safeguards and uncouples neuronal differentiation from mitotic resistance.

Objective To investigate the effects of sphingosine-1- phosphate receptor 1 (S1PR1) changes on the proliferation of endogenous neural stem cells (NSCs) in hippocampus after traumatic brain injury (TBI). Methods Rat TBI models were constructed by the means of controlled cortical injury. A total of 72 rats were included and randomly divided into four groups: sham, TBI, TBI+ SEW (TBI+ S1PR1 agonist SEW2871 intervention) and TBI+ VPC group (TBI+ S1PR1 antagonist VPC23019 intervention), with 18 rats per group. The TBI model was induced by a control cortical injury device. The injured rats in TBI+ SEW group and TBI+ VPC group were respectively administrated with S1PR1 agonist SEW2871 and antagonist VPC23019 at scheduled time points after TBI. Hippocampal S1PR1 expression was detected by Western-blotting and the proliferation of NSCs was assessed by double-labeled immunofluorescence staining at days 7, 14 and 21 after injury. Results At days 7, 14 and 21 after TBI, the hippocampal S1PR1 levels and NSCs proliferation amounts in sham, TBI, TBI+ SEW and TBI+ VPC groups were evidently different (P<0.05). In particular, the outstanding changes among the four groups above occurred at 7 d after injury were as following: S1PR1 expression in TBI group significantly increased by 1.56 times compared with that in sham group, and it was respectively up-regulated by 66.67% in TBI+ SEW group and down-regulated by 20.29% in TBI+ VPC group (P<0.05). The number of NSCs proliferation in TBI group was 2.08 times more than that in sham group, and it increased by 36.75% in TBI+ SEW group and reduced by 18.77% in TBI+ VPC group(P<0.05). Conclusion The expression of S1PR1 is closely associated with the proliferation of NSCs in hippocampus after TBI, indicating that S1PR1 activation may be an effective strategy to improve the post-traumatic neurogenesis. Key words: Brain injuries; Neural stem cells; Nerve regeneration; Sphingosine-1-phosphate receptor 1

Cell proliferation is coupled with nutrient availability. If nutrients become limited, proliferation ceases, because growth factor and/or PI3-kinase activity levels become attenuated. Here, we report an exception to this generality within a subpopulation of Drosophila neural stem cells (neuroblasts). We find that most neuroblasts enter and exit cell cycle in a nutrient-dependent manner that is reversible and regulated by PI3-kinase. However, a small subset, the mushroom body neuroblasts, which generate neurons important for memory and learning, divide independent of dietary nutrient conditions and PI3-kinase activity. This nutrient-independent proliferation is regulated by Eyeless, a Pax-6 orthologue, expressed in mushroom body neuroblasts. When Eyeless is knocked down, mushroom body neuroblasts exit cell cycle when nutrients are withdrawn. Conversely, when Eyeless is ectopically expressed, some non-mushroom body neuroblasts divide independent of dietary nutrient conditions. Therefore, Eyeless uncouples MB neuroblast proliferation from nutrient availability, allowing preferential neurogenesis in brain subregions during nutrient poor conditions.

Centriole Mediated Neurogenesis of OSN in Fish

Development of Neurogenesis in the Adult Mammalian

Background The early growth response gene-1(Egr-1) is considered to be a triggering mechanism that maintains long term potentiation and activates neurogenesis. The expression of Egr-1 protein is closely associated with the consolidation, reconsolidation and extinction of long term memory. Objective Providing potential research targets for studying the mechanism and treatment of postoperative cognitive dysfunction. Content We review the structure, expression pattern of Egr-1 protein and its roles in learning and memory. Trend Egr-1 plays different roles in different phases of memory, but the specific signaling pathways and their relationship with postoperative cognitive dysfunction deserve further clarification. Key words: The early growth response gene-1; Signal pathway; Learning and memory

With the development of modern radiotherapy techniques, radiotherapy has been widely used in the multimodality therapy for various malignant tumors, including head and neck cancers such as nasopharyngeal cancer and laryngeal cancer. A combination of surgery and radiochemotherapy significantly improves patients’ cure rate and survival time; however, with the increase in survival time, some patients receiving radiotherapy develop marked cognitive impairment. Ionizing radiation-induced cognitive impairment mainly manifests as hippocampus-dependent cognitive impairment, which is associated with inhibited hippocampal neurogenesis due to ionizing radiation. Therefore, it is necessary to investigate the mechanisms of the inhibition of hippocampal neurogenesis by ionizing radiation. This article reviews the molecular mechanism of neurogenesis disorders induced by ionizing radiation. Key words: Radiation; Neurogenesis; Neural stem/progenitor cell; Brain microenviorment; Inflammation

Objective To investigate the effect of Hes1 upregulation by using an adonoviral vector containing mouse Hes1 gene in adult hippocampal neurogenesis following traumatic brain injury (TBI), a Morris water maze (MWM) test was employed to investigate the spatial learning and memory capacity of adult mice following injury. Methods One hundred and sixty mice were randomly allocated into four groups: sham-PBS group, sham-PBS-TBI group, Ad5-enhanced green fluorescent protein (EGFP)-TBI group, Ad5-Hes1-TBI group. The TBI model mouse was subjected to lateral fluid percussion injury of (202±2) kPa using a pre-calibrated fluid percussion injury device. Then, Ad5-mRNA and PBS were stereotaetic injected into the hippocampus of the adult C57BL/6 mice and their expressions in the hippocampus were detected. Western blotting and real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) methods were employed to detect the expression level of Hes1 on day 3 following TBI. We performed BrdU or DCX immunofluorescence staining on day 3 or 7 post TBI, to investigate the effect of Hes1 upregulation in adult hippocampal neurogenesis following TBI. Results FQ-PCR and Western blotting analysis suggested that Hes1 was up-regulated in overexpression group at mRNA (1.87±0.13 vs. 0.97±0.13, P=0.025) on day 3 post TBI and protein level; Immunofluorescence staining showed that a significant decrease in the total number of BrdU (+ ) and DCX (+ ) cells from the animals with Ad5-mHes1 treated on day 3 or 7 post injury. Morris water maze (MWM) test confirmed that Hes1 overexpression did not lead to a statistically significant change in EL and the target quadrant (P=0.062). Conclusion These results strongly suggested that increased expression of Hes1 may inhibit adult neurogenesis in DG of hippocampus after TBI and did not lead to a statistically significant change in the spatial learning and memory capacity of adult mice following injury. Key words: Hes1; Adult neurogenesis; Traumatic brain injury; Morris water maze

Objective To observe the effect of maternal separation(MS)on the expression of glucocorticoid receptor(GR)and doublecortin(DCX)in hippocampus and prefrontal cortex of young mice. Methods Fifteen pregnant mice were randomly divided into 5 groups: the experimental group(3 d, 7 d, 14 d, 21 d)and the control group, n=3 in each group. Neonatal mice in experimental group were separated from mother for 3 h once a day, and the mice in control group were caged with mother without any processing after birth. All mice were weaned in postanal day 23. Separating female and male mice, and the male mice were killed and the brains were taken in postanal day 42. The expression and distribution of GR and DCX in hippocampus and prefrontal cortex were determined by immunohistochemical staining and Image J image analysis technique. Results The average optical density values of GR positive cells in hippocampus and prefrontal cortex, the average optical density values of DCX positive cells in hippocampal dentate gyrus subgranular zone in 3 d, 7 d, 14 d and 21 d group were(GR in hippocampus: 3 d((0.332±0.054)OD/μm2, 7 d(0.258±0.045)OD/μm2, 14 d(0.197±0.043)OD/μm2, 21 d(0.164±0.053)OD/μm2), (GR in prefrontal cortex: 3 d(0.356±0.043)OD/μm2, 7 d(0.278±0.041)OD/μm2, 14 d(0.220±0.039)OD/μm2, 21 d(0.157±0.034)OD/μm2)and(DCX in hippocampus: 3 d(0.193±0.020)OD/μm2, 7 d(0.146±0.033)OD/μm2, 14 d(0.110±0.032)OD/μm2, 21 d(0.060±0.017)OD/μm2)were lower than those in control group, which showed a decreasing trend with the increase of seperation time, and the average optical density values in 7 d, 14 d and 21 d group were obviously lower than those in control group(P<0.05). The average optical density values had statistical significance among the experimental groups(P <0.05). Conclusion MS can cause the decrease of GR in hippocampus and prefrontal cortex and reduce neurogenesis in the hippocampal dentate gyrus subgranular zone in young mice. It shows that the longer the seperation time, the greater the effect on hypothalamic-pituitary-adrenal(HPA) axis and neurogenesis. Key words: Maternal separation; Hippocampus; Prefrontal cortex; Glucocorticoid receptor; Doublecortin