Dopaminergic neurons are one of the major neuronal components in the brain. Mesencephalon dopamine (DA) neurogenesis takes place in the ventricular zone of the floor plate, when DA progenitors divide to generate postmitotic cells. These cells migrate through the intermediate zone while they differentiate and become DA neurons on reaching the mantle zone. However, neurogenesis and neuronal migration on dopaminergic neurons remain largely unexplored in the mesencephalon development. This study presents neurogenesis and neuronal migration patterns of dopaminergic neurons during mesencephalic development of the mouse. Neurons from embryonic day (E) 10–14 were labelled by a single injection of 5-bromodeoxyuridine and immunohistochemistry was performed. The neurogenesis occurred mainly at the E10 and E11, which was uniformly distributed in the mesencephalic region, but neurons after E13 were observed only in the dorsal mesencephalon. At the postnatal day 0 (P0), E10 generated neurons were spread out uniformly in the whole mesencephalon whereas E11-originated neurons were clearly depleted in the red nucleus region. DA neurons mainly originated in the ventromedial mesencephalon at the early embryonic stage especially E10 to E11. DA neurons after E12 were only observed in the ventral mesencephalon. At E17, E10 labelled neurons were only observed in the substantia nigra (SN) region. Our study demonstrated that major neurogenesis occurred at E10 and E11. However, neuronal migration continued until neonatal period during mesencephalic development.

Traditionally, Centella asiatica leaf extracts are used to treat neurodegenerative diseases in India. Centella asiatica is reportedly used to enhance memory and treat dementia, but its promoting effect on neural stem cell differentiation has not been studied yet. In the present study, we investigated whether or not Centella asiatica leaf extracts act on neuronal precursor cells and neuronal cell lines to induce neuronal differentiation, neurite outgrowth, and neuroprotection. The neurogenesis-promoting potential of Centella asiatica leaf extracts was determined by differentiation assay on neural stem cells isolated from mouse embryos and PC12 cell lines. To understand the contribution of specific neural cell types towards increase after Centella asiatica treatment, neural stem cells were differentiated into various neural subtypes and checked by Western blotting using neural cell lineage-specific antibody markers. Neuroprotective activity of Centella asiatica was analyzed in PC12 cells exposed to 100 μM of H2O2. Cell growth was analyzed by MTT assay while cell death was analyzed by Western blotting detection of apoptosis-related proteins. Cells treated with Centella asiatica had significantly longer primary and secondary neurites as well as a higher number of neurites per cell compared to control cells. Expression levels of TUBBIII, TH, NF, and BDNF increased upon Centella asiatica treatment, suggesting that Centella asiatica has a neurogenesis-promoting effect. Centella asiatica also inhibited oxidative stress-induced neural cell damage through regulation of apoptosis- and cell cycle-related proteins. Thus, leaf extracts of Centella asiatica might promote neurogenesis, neuroregeneration, and neuroprotection in the context of neurodegenerative diseases.

Mammalian Emx2. a homeobox tra nscripti on factor‘ is continuoll s ly expressecl in aclll lt neural s tem cell s of the b.ippo campal c1enclate gyrus (HDG) a f'ter blrth 1'0 c1ate‘ roles 01' Emx2 a ncl its llnderlying rnecha ni s rn in r eg비 atin g acl lllt neuro - genesis from neural stem cell aft er bi rth is still obscure. 1'he present experiment is aimed to elucidate role 01' Emx2 in regulating adll lt neurogenesis from neural s tem cell of HDG using nestin-Emx2 transgenic mouse (N-E2 1'G) and heterozygous Emx2 KO mouse (1-l-E2 KO) . HDG g ranlllar cell layer where new born neurons proclllced from adult neural stem cell migrate. is thin with low cell c1ens ity in N-E2 1'G but tbick with high cell density in H-E2 KO, compared to wild type mice (\\끼') . Number of DCX , a new born nellron marker. -positive cells is less in N-E2 1'G but more in l-l-E2 KO. comparecl to W1'. Ki67 (whole cell cycle marker) 01' BrclU (S-phase marker) 一positive cells is less in N-E2 1'G bllt morc in l-l-E2 KO and BrdU-positive cells/ Ki 67ratio is higher in N-E2 1'G but lower in H-E2 KO. NeuN (a mature n e llro삐 marker) a ncl BrdU-dollble positive cells is lUore in N- E2 TG bllt GFAP (a glial cell marker) ancl BrdU- dollble positive cells is more in ]-]- E2 KO. compa recl to WT 4wks after BrclU is aclmin istratecl one ti me per c1ay for 5days‘ Migrating c1egree of BrdU-positive cells is lower in N-E2 TG but higher in ]-]-E2 KO 4wks after BrclU is administratecl one t ime per day for 5days. Active casepase 3-positive cells is more in ]-]DG 01' the N-E2 TG but no changes in ]-]-E2 KO. 4 wks after CAG- GFP- PRE vector was inj ected in hippocampus. GFP-positive new born n e urons from aclult neural stem cell have less c1endritic branches in N-E2 1'G but more c1endritic branches in H-E2 KO‘ comparecl to the WT From these results. Emx2 transcription factor inhibits adult neurogenesis f'rom nellral stem cell of HDG throllgh reducing neural stem cell proliferation. new born cell survival. ce ll migration. ancl matllrat ion

The present study was aimed at investigating the effect of swimming training on brain function after focal cerebral ischemia in rats. Therefore, this study was examined on neurogenesis in dentate gyrus of hippocampus using 5-bromo-2'-deoxyuridine (BrdU) to label proliferating cells and assessed the neurological response following focal cerebral ischemia in rats using neurological motor behavioral test. In an observer-blinded fashion, twenty male Sprague-Dawley (280~310 g, 7 weeks old) rats were divided into four groups: MCAO plus swimming group (ME, =5), MCAO plus control group (MC, =5), SHAM plus swimming group (SE, =5), SHAM plus control group (SC, =5). The results of this study were as follows: 1) The limb placing time before and after swimming in the ME group were significantly longer than the MC group (p<.05), the SE group were significantly longer than the SC group (p<.01). 2) The balance beam scores before and after swimming in the ME group was higher than the SE group, the MC group was higher than the SC group but was not significantly different (p>.001). 3) The foot fault index before and after swimming training in ME group was significantly lower (i.e., improved) than the MC group (p<.001) and the SE group (p<.001), the SE group was significantly lower (i.e., improved) than the SC group (p<.001). 4) The mean number of BrdU-positive cells in the dentate gyrus in the ME group was significantly higher than the MC group (p<.001) and the SE group (p<.01). The MC group and the SE group was significantly higher than the SC group (p<.001). 5) There was significantly correlation between limb placing time and number of BrdU-positive cells on swimming training, there was positive correlation (r=.807, p<.0001) and between foot fault index and BrdU-positive cells number, there was negative correlation (r=-.503, p<.05). However, between balance beam scores and BrdU-positive cells number, there was no correlation. In conclusion, the present study demonstrates that the role of swimming training improves behavioral motor function probably by enhancing cell proliferation in that hippocampus. This study provides a model for investigating the stroke rehabilitation that underlies neurogenesis and functional ability.

Endocytosis of the Notch ligand, DeltaD, by mind bomb1 is indispensable for activation of Notch in cell fate determination, proliferation, and differentiation during zebrafish neurogenesis. Loss of mind bomb1 activity as an E3 Ubiquitin ligase causes the accumulation of deltaD at the plasma membrane and results in the ectopic neurogenic phenotype by activation of Notch in early zebrafish embryogenesis. However, the regulatory mechanism of deltaD during neurogenesis is not identified yet. This study aims to analyze the pathway of mib1 and deltaD after endocytosis in vivo during zebrafish embryogenesis. Mind bomb1 and deltaD are co-localized into autophagosome and mutant form of mind bomb1 fails to cargo deltaD into autophagosomes. These findings suggest that mind bomb I mediates deltaD regulation by autophagy in an ubiquitin-dependent manner during zebrafish embryogenesis.