In recent decades, scientists in Asian and Western countries have been paying great attention to ginseng research. Today, more than 200 ginsenosides and non-saponin constituents have been isolated and identified. Ginsenosides show biological activities only after being deglycosylated by intestinal bacteria. Aglycone protopanaxadiol and protopanaxatriol show the highest bioactivities. According to literature, the noticeable action of ginseng is that of delaying aging and especially increasing the nootropic effect, and it was found for the first time that Rg1 could increase hippocampal neurogenesis in vitro and in vivo under physiological and pathological circumstances. This is one of primary mechanisms underlying many of its pharmacological actions on the central nervous system. Rg1 was further shown to improve learning and memory in normal rats and mice. The nootropic signaling pathway has also been carried out in normal rats, and the Rg1-induced signaling pathway is similar to the memory formation that occurs in mammals, suggesting that Rg1 may have a potential effect in increasing intellectual capacity in normal people. Comparisons of chemical structures and pharmacologic functions between Panax ginseng and Panax quiquefolium were carried out by many scientists. The conclusion is that each has its own characteristics. There is no superiority or inferiority to the other.
Animals ; Cognition ; drug effects ; Ginsenosides ; pharmacology ; Humans ; Learning ; drug effects ; Memory ; drug effects ; Mice ; Neovascularization, Physiologic ; Neurogenesis ; Neuronal Plasticity ; drug effects ; Panax ; chemistry ; Rats ; Signal Transduction ; drug effects

OBJECTIVETo study the effect of Lycium barbarum polysaccharides (LBP) on neurogenesis and learning & memory of manganese poisoning mice.

METHODSHealthy adult Kunming mice were divided into 5 groups, the control group (A), the manganese poisoning (by manganese chloride peritoneal injection) group (B), the manganese poisoning and treated with gastric perfusion of high, medium, low dosage LBP groups (C, D and E). The spatial learning & memory capacity of mouse was determined by Morris water maze training test. The neurogenetic cells were labelled with bromodeoxyuridine (BrdU) and detected by immunohistochemistry.

RESULTSThe average escape latency was significantly higher and the times of passing through platform lower in group B than those in group A (P<0.05). BrdU positive cells in groups C, D and E were significantly more than those in group B (P<0.05).

CONCLUSIONLBP could enhance the learning & memory capability of the manganese poisoning mice by promoting neurogenesis in hippocampus.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Learning ; drug effects ; Male ; Manganese Poisoning ; Memory ; drug effects ; Mice ; Mice, Inbred Strains ; Neurogenesis ; drug effects

OBJECTIVETo investigate the influence of exposure to different concentrations of ethanol on neural progenitor cells and the differentiation of neurons and glial cells in zebrafish embryos.

METHODSZebrafish embryos were exposed to 1%, 2%, and 2.5% (V/V) ethanol at 5 hpf by adding ethanol to the egg water. In situ hybridization and real-time PCR were used to detect the changes in the mRNA expression profiles of the markers of different cells to examine the effects of alcohol on neural development.

RESULTSThe number of neural precursor cells, neurons and mature glial cells was significantly reduced in the zebrafish embryos following ethanol exposure, and this reduction became more prominent as the ethanol concentration increased. The expression of the early glial marker slc1a3a was down-regulated in the spinal cord but increased in the brain after exposure to increased ethanol concentrations. The expression of the mature glial markers was significantly lowered in response to exposure to increasing ethanol concentrations.

CONCLUSIONSEthanol can reduce neural precursor cells and inhibits neuronal and glial differentiation in zebrafish embryos.

Animals ; Brain ; Cell Differentiation ; drug effects ; Embryo, Nonmammalian ; drug effects ; Ethanol ; adverse effects ; Neural Stem Cells ; drug effects ; Neurogenesis ; drug effects ; Neuroglia ; drug effects ; Neurons ; drug effects ; Spinal Cord ; Zebrafish ; embryology

OBJECTIVETo investigate the effects of polygala on leaning and memory and the expression of Microtubule associated protein on manganese poisoned mice.

METHODS60 female Kunming mice were randomly and equally divided into 5 group. They are normal control group (CG), manganese poisoned group (MG), manganese poisoned with polygala high dose group (MHG), manganese poisoned with polygala middle dose group (MMG), manganese poisoned with polygala low dose group (MLG). The model of manganese poisoned mice was prepared of the way of intraperitoneal injection of manganese chloride (MnCl2 15 mg/kg), the spatial learning and memory ability was tested by Morris water maze, the Doublecortin (DCX) was tested by the way of immunofluorescent staining in the SVZ and SGZ.

RESULTIn the navigation test, compared with MG, the escape latency of MHG, MMG and MLG were significantly decreased (P < 0.05), in space exploration experiments, MHG, MMG, MLG compared with MG, the number increased significantly across platforms (P < 0.05). compared with MG, the DCX expression of MHG, MMG and MLG were significantly increased (P < 0.05).

CONCLUTIONThe leaning and memory ability of manganese poisoned mice can be improved by the polygala, and the mechanism may be related to promote the expression of DCX and neurogenesis in the brain.

Animals ; Female ; Manganese Poisoning ; drug therapy ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Microtubule-Associated Proteins ; drug effects ; Neurogenesis ; drug effects ; Neuropeptides ; drug effects ; Plant Extracts ; pharmacology ; Polygala ; chemistry

Inducible cyclooxygenase-2 (COX-2) has received much attention because of its role in neuro-inflammation and synaptic plasticity. Even though COX-2 levels are high in healthy animals, the function of this factor in adult neurogenesis has not been clearly demonstrated. Therefore, we performed the present study to compare the effects of pharmacological and genetic inhibition of COX-2 on adult hippocampal neurogenesis. Physiological saline or the same volume containing celecoxib was administered perorally every day for 5 weeks using a feeding needle. Compared to the control, pharmacological and genetic inhibition of COX-2 reduced the appearance of nestin-immunoreactive neural stem cells, Ki67-positive nuclei, and doublecortin-immunoreactive neuroblasts in the dentate gyrus. In addition, a decrease in phosphorylated cAMP response element binding protein (pCREB) at Ser133 was observed. Compared to pharmacological inhibition, genetic inhibition of COX-2 resulted in significant reduction of neural stem cells, cell proliferation, and neuroblast differentiation as well as pCREB levels. These results suggest that COX-2 is part of the molecular machinery that regulates neural stem cells, cell proliferation, and neuroblast differentiation during adult hippocampal neurogenesis via pCREB. Additionally, genetic inhibition of COX-2 strongly reduced neural stem cell populations, cell proliferation, and neuroblast differentiation in the dentate gyrus compared to pharmacological inhibition.
Animals ; Celecoxib/*pharmacology ; Cell Differentiation/drug effects/physiology ; Cell Proliferation/drug effects/physiology ; Cyclooxygenase 2/*genetics/metabolism ; Cyclooxygenase 2 Inhibitors/*pharmacology ; Dentate Gyrus/drug effects/*physiology ; Male ; Mice ; Mice, Knockout ; Neural Stem Cells/drug effects/physiology ; Neurogenesis/drug effects

In this study, we investigated the effects of chronic aluminum (Al) exposure for 10 weeks on cell proliferation and neuroblast differentiation in the hippocampus of type 2 diabetic rats. Six-week-old Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were selected and randomly divided into Al- and non-Al-groups. Al was administered via drinking water for 10 weeks, after which the animals were sacrificed at 16 weeks of age. ZDF rats in both Al- and non-Al-groups showed increases in body weight and blood glucose levels compared to ZLC rats. Al exposure did not significantly affect body weight, blood glucose levels or pancreatic β-cells and morphology of the pancreas in either ZLC or ZDF rats. However, exposure to Al reduced cell proliferation and neuroblast differentiation in both ZLC and ZDF rats. Exposure to Al resulted in poor development of the dendritic processes of neuroblasts in both ZLC and ZDF rats. Furthermore, onset and continuation of diabetes reduced cell proliferation and neuroblast differentiation, and Al exposure amplified reduction of these parameters. These results suggest that Al exposure via drinking water aggravates the impairment in hippocampal neurogenesis that is typically observed in type 2 diabetic animals.
Aluminum/*toxicity ; Animals ; Blood Glucose/analysis ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Type 2/*pathology ; Disease Models, Animal ; Hippocampus/*drug effects ; Neurogenesis/*drug effects ; Random Allocation ; Rats, Zucker

This paper was aimed to investigate the effect of gastrodin( GAS) on hippocampal neurogenesis after cerebral was chemic and to explore its mechanism of action related to NO. The cerebral ischemia model of C57 BL/6 mice was established by bilateral common carotid artery occlusion. The pathological changes in hippocampal CA1 region and the cognitive function of mice were assessed by HE staining and Morris water maze test,respectively. The count of Brd U/Neu N positive cells in dentate gyrus was detected by immunofluorescence assay. The NOS activity and the NO content were determined by colorimetric and nitrate reduction methods,respectively.The level of c GMP was measured by ELISA kit,and the PKG protein expression was tested by Western blot. On postoperative day 8,the hippocampal CA1 pyramidal neurons of mice showed irregular structure,with obvious nuclear pyknosis,loose cell arrangement and obvious decrease in the number of neurons. On postoperative day 29,the spatial learning ability and memory were decreased. These results indicated cerebral ischemia in mice. Meanwhile,the Brd U/Neu N positive cells were increased significantly in ischemic mice,indicating that neurogenesis occurred in hippocampus after cerebral ischemia. Treatment with different doses of gastrodin( 50 and 100 mg·kg-1) significantly ameliorated the pathological damages in the CA1 region,improved the ability of learning and memory,and promoted hippocampal neurogenesis. At the same time,both the NOS activity and the NO concentration were decreased in model group,but the c GMP level was increased,and the PKG protein expression was up-regulated. Gastrodin administration activated the NOS activity,promoted NO production,further increased c GMP level and up-regulated PKG protein expression. These results suggested that gastrodin can promote hippocampal neurogenesis after cerebral ischemia and improve cognitive function in mice,which may be related to the activation of NO-cGMP-PKG signaling pathway.
Animals ; Benzyl Alcohols/therapeutic use* ; Brain Ischemia/drug therapy* ; CA1 Region, Hippocampal/drug effects* ; Cognition ; Glucosides/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Neurogenesis ; Signal Transduction

OBJECTIVETo investigate the effect of licorice flavonoid (LF) on kainic acid (KA)-induced seizure in mice and its mechanism.

METHODSMale adult ICR mice were injected with 25 mg/kg KA to induce temporal lobe seizure. LF was administrated 7 d before seizure induction (pre-treatment) or 24 h after seizure induction (post-treatment) for 7 d. Acute seizure latency, seizure stage and duration were observed and compared between LF- and vehicle-treated mice. From d2 on, mice with status epilepticus were video-monitored for spontaneous seizures, 10 h/d for 6 w. Immunohistochemical analysis of BrdU and Timm staining was conducted to detect the neurogenesis and mossy fiber sprouting, respectively.

RESULTSNo significant difference was observed in acute seizure latency, seizure stage and duration between LF-and vehicle-treated mice. KA-induced acute seizure resulted in spontaneous seizure in mice, and the seizure frequency was increased with time. Pre- and post-treatment with LF decreased seizure frequency from w3 after modeling [(0.58±0.15)/d, (0.38±0.38)/d vs (1.23±0.23)/d, P <0.05]. Furthermore, KA-induced seizure resulted in robust neurogenesis and mossy fiber sprouting, while treatment with LF both pre- and post- KA injection significantly inhibited neurogenesis (15.6±2.6, 17.1±3.1 vs 28.9±3.5, P <0.05) and mossy fiber sprouting (1.33±0.31, 1.56±0.42 vs 3.0±0.37, P <0.05).

CONCLUSIONLF has no significant anti-seizure effect. However, it can decrease epileptogenesis through inhibition of neurogenesis and mossy fiber sprouting.

Animals ; Disease Models, Animal ; Flavonoids ; pharmacology ; Glycyrrhiza ; chemistry ; Kainic Acid ; adverse effects ; Male ; Mice ; Mice, Inbred ICR ; Mossy Fibers, Hippocampal ; drug effects ; Neurogenesis ; drug effects ; Seizures ; chemically induced ; drug therapy ; Status Epilepticus ; drug therapy

OBJECTIVETo establish an optimized primary drug screen model of neuronal differentiation using P19 embryonal carcinoma cells.

METHODSThe final concentration of retinoid acid (RA), days of suspension culture, manner of adherent culture, suitable cell density and adherent culture medium were tested, respectively. Two stages of neuronal differentiation were examined based on morphological changes and immunocytochemistry analysis of neuronal specific protein β-tubulin III.

RESULTSOn d 8 of differentiation culture, neuron-like cells were observed with final concentration of 1 μmol/L RA. Neuron-like network was formed on d 16 of neuronal differentiation. β-tubulin III was positively stained on both stages, indicating P19 cells were differentiated into neurons.

CONCLUSIONThe model using RA to induce P19 embryonic carcinoma cells to differentiate into neuron-like cells has been successfully established, which may provide a rapid, phenotypic cell-based platform for primary screening of neurogenesis-promoting drugs.

Animals ; Cell Culture Techniques ; Cell Differentiation ; drug effects ; physiology ; Cell Line ; Embryonal Carcinoma Stem Cells ; cytology ; drug effects ; Mice ; Neurogenesis ; drug effects ; Neurons ; cytology ; metabolism ; Phenotype ; Tretinoin ; pharmacology ; Tubulin ; metabolism

OBJECTIVETo observe the regulatory effects of psoralen, oleanolic acid, and stilbene glucoside, three active components of psoralea fruit, glossy privet fruit and tuber fleeceflower root respectively, on Aβ25-35induced self-renewal and neuron-like differentiation of neural stem cells (NSCs).

METHODSEmbryonic NSCs werein vitro isolated and cultured from Kunming mice of 14-day pregnancy, and randomly divided into the control group, the Aβ25-35 group, the Aβ25-35 +psoralen group, the Aβ25-35 +oleanolic acid group, and the Aβ25-35 + stilbene glucoside group. The intervention concentration of Aβ25-35 was 25 µmol/L, and the intervention concentration of three active components of Chinese medicine was 10(-7)mol/L. The effect of three active components of Chinese medicine on the proliferation of NSCs was observed by counting method. The protein expression of Tubulin was observed by Western blot and immunofluorescence. The ratio of Tubulin+/DAPI was caculated. Results Compared with the control group, the sperical morphology of NSCs was destroyed in the Aβ25-35 group, the counting of NSCs, the expression of Tubulin protein, and the ratio of Tubulin /DAPI all decreased (P <0.01, P <0.05). Compared with the Aβ25-35 group, the counting of NSCs, the expression of Tubulin protein, and the ratio of Tubulin + /DAPI all increased in the three Chinese medicine treated groups (P <0. 01, P <0. 05).

CONCLUSIONS25 µmol/L Aβ25-35 could inhibit self-renewal and neuron-like differentiating of NSCs. But psoralen, oleanolic acid, and stilbene glucoside could promote self-renewal of NSCs and neuron-like differentiation.

Amyloid beta-Peptides ; physiology ; Animals ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Embryo, Mammalian ; Female ; Mice ; Neural Stem Cells ; Neurogenesis ; drug effects ; Neurons ; cytology ; Peptide Fragments ; physiology ; Pregnancy