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Objective@#Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood; however, the underlying mechanism has not been established.@*Methods@#SD rats were exposed to propofol on postnatal day 7 (PND-7). Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus (DG). The expression of p-Akt and p27 were measured by western blotting. The Morris water maze, novel object recognition test, and object location test were used to evaluate neurocognitive function 2-month-old rats.@*Results@#Phosphorylation of Akt was inhibited, while p27 expression was enhanced after neonatal exposure to propofol. Propofol also inhibited proliferation of neural stem cells (NSCs) and decreased differentiation to neurons and astroglia. Moreover, the neurocognitive function in 2-month-old rats was weakened. Of significance, intra-hippocampal injection of the Akt activator, SC79, attenuated the inhibition of p-AKT and increase of p27 expression. SC79 also rescued the propofol-induced inhibition of NSC proliferation and differentiation. The propofol-induced neurocognition deficit was also partially reversed by SC79.@*Conclusion@#Taken together, these results suggest that neurogenesis is hindered by neonatal propofol exposure. Specifically, neonatal propofol exposure was shown to suppress the proliferation and differentiation of NSCs by inhibiting Akt/p27 signaling pathway.
Subject(s)
Animals , Rats , Cell Proliferation , Hippocampus/metabolism , Neural Stem Cells , Propofol/toxicity , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Signal TransductionABSTRACT
Objective:To explore the effects of chronic restraint stress (CRS) on the abilities of spatial learning and memory and the levels of excitatory amino acids in the hippocampal dentate gyrus (DG) in the old rats,and to investigate the neurochemical mechanism of CRS in affecting the spatial learning and memory abilities.Methods:Sixteen male SD rats (18 months old) were randomly divided into control group (n =8) and CRS group (n=8),and the rats in CRS group received CRS 2 h every day for 30 d.And then the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test,and the extracellular levels of excitatory amino acids including asparate (Asp) and glutamate (Glu) in the DG were simultaneously determined by in vivo microdialysis and HPLC.The levels of corticosterone (CORT) and epinephrine (EPI) in serum of the rats wereexamined by ELISA assay.Results:In CRS group,the escape latencies on the 2nd-4th days were significantly increased and the percentage of time spent in target quadrant on the 5th day was markedly decreased in MWM test compared with control group (P＜0.05).Compared with before training,the extracelluar level of Asp in the DG in control group was significantly increased on the 2nd day in MWM test;compared with control group,the extracelluar level of Asp in the DG in CRS group was significantly decreased on the 3rd day in MWM test (P＜0.05).Compared with before training,the Glu levels in the DG in MWM test in both control and CRS groups were markedly increased (P＜0.05),but there was no significant difference between two groups (P＞0.05).Compared with control group,the levels of CORT and EPI in the serum of the rats in CRS group were significantly increased (P＜0.05).Conclusion:CRS impairs the spatial learning and memory abilities in the old rats,which may be related to the decrease of Asp level in the hippicampal DG of the rats.
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Objective: To observe the changes of dopamine (DA) levels in the hippocampal dentate gyrus (DG) region of the rats during the establishment and extinction process of active avoidance conditioned reflex, and to investigate the effect of D1 receptor in the active avoidance learning of the rats and its mechanism. Methods: A total of 24 male SD rats were randomly divided into non-training group, training group, control group and SCH group (n= 6). The rats in training group were trained for active avoidance whereas the rats in non-training group were only put into the shuttle box without training, and then the DA levels in extracellular fluid in DG region of the rats in two groups were measured. In control and SCH groups, the saline or SCH-23390 was injected into the DG region of the rats before the active avoidance training, and then the glutamate (Glu) levels and the field excitatory postsynaptic potential (fEPSP) amplitudes in extracellular fluid in DG region of the rats in two groups were examined. The rates of active avoidance of the rats were recorded by behavioral analysis system of the shuttle box. The levels of DA and Glu in DG region of the rats were measured by microdialysis and HPLC techniques, and the amplitude of fEPSP in DG region of the rats was examined by electrophysiological recording. Results: The DA level in DG region of the rats in training group was gradually increased during the establishment process and was gradually decreased during the extinction process of conditioned reflex; compared with the 1st day, the DA level in DG region of the rats on the 5th day was markedly increased (P0. 05). In control group, the rats reached the establishment criterion on the 5th day (active avoidance rate > 65%) and reached the criterion of extinction on the 7th day (active avoidance rate 0. 05). Compared with control group, the Glu level and fEPSP amplitude of the rats in SCH group on the 5th day were markedly decreased (P<0. 05). Conclusion: DA in hippocampal DG region of the rats can facilitate the active avoidance learning via activation of D1 receptors, and its mechanism is associated with the enhancement of Glu level and synaptic transmission efficiency.
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Objective To investigate the neurodevelopmental toxicity of ACR by studying the expression of DCX and GAP-43 in the hippocampal dentate gyrus of rats after maternal exposure to acrylamide. Methods Pregnant rats were randomly divided into low-dose ACR(4.5 mg/kg),medium-dose(9 mg/kg),high dose groups(18 mg/kg)and the control group(0 mg/kg),8 in each group,and were exposed to toxicant from gestation-al day 15 to postnatal day 13. All rats and their pups were killed on postnatal day 14. ABC immunohistochemistry was used to detect the expression of GFAP in the hippocampus of mother rats and offspring. Results Compared with the control group,the expression of DCX and GAP-43 in hippocampus dentate gyrus of the pregnant rats in middle and high dose groups was significantly decreased(P < 0.05). Conclusion ACR may interfere with the growth and development of neurons by reducing the expression of DCX and GAP-43.
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OBJECTIVE: To observe the effect of acupuncture and moxibustion (AM) on learning-memory ability and expression of amyloid beta (Aβ) in the hippocampal dentate gyrus (DG) of Alzheimer's disease (AD) rats, so as to explore its mechanism underlying improvement of AD. METHODS: Forty male Wistar rats were randomly divided into normal, sham operation, model and AM groups (n＝10 in each). The AD model was established by bilateral hippocampal injection of Aβ1-42(5 µL). The AM was applied at "Baihui" (GV 20) and "Shenshu" (BL 23) for 15 min, once daily for 12 times. Morris water maze tests were used to assess the rats' learning-memory ability. The levels of serum Aβ1-42 and Aβ internalizing enzymes including transthyretin (TTR), lipoprotein lipase (LPL), alpha 2 macroglobulin (α 2M) and apolipoprotein E (ApoE) were detected by ELISA. The expression of Aβ1-42 in the hippocampal DG was detected by immunohistochemistry. RESULTS: Compared with the sham operation group, the average escape latency of location navigation test was significantly prolonged in the first 5 days and the last 3 days (P0.05). CONCLUSION: AM can improve the learning-memory ability of AD rats, which may be related to its effects in up-regulating the contents of serum Aβ internalizing enzymes and promoting the clearance of hippocampal Aβ. It suggests a protective role of AM on hippocampal neurons.
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With the increasing size of aging population all over the world, the incidence of Alzheimer's disease has reached to the highest level in many developed countries. However, the etiology of Alzheimer's disease remains largely unknown especially in the biological mechanism. Up to now, it is still a challenge that the disease can't be controlled by the approved clinical medicines. As a result, new therapeutic strategies are urgently needed to prevent and cure Alzheimer's disease. The hippocampus area is associated with learning, memory, cognitive regulation in the central nervous system, which is closely related to Alzheimer's disease. Adult neurogenesis in hippocampal area allows new neuronal cells to emerge in the central nervous system. The brain's plasticity is achieved in some sense. This review focuses on the progress in the study of variety of compounds in promotion of neurogenesis in adult hippocampal area in recent years. The potential of these compounds may shed a light on postponing the occurring of Alzheimer's disease or even curing it.
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BACKGROUND: Newborn neurons have bean shown to induce long-term potentiation (LTP). Activation of N-methyl-D-aspartic acid (NMDA) receptor subunit NR2B plays an important role in mature neurons-induced LTP. But there have been no reports addressing on the effects of NR2B activation on newborn neuron-induced LTP.OBJECTIVE: To investigate the effects of NR2B receptor antagonist Ro25-6981 on LTP induced by newborn neurons in adult rat dentate gyrus.DESIGN, TIME AND SETTING: An electrophysiological recording trial was performed at the Department of Neuroblology,Shanxi Medical University from February to June 2007.MATERIALS: Twenty-six male Wistar rats, aged 3 months, were provided by Laboratory Animal Center, Shanxi Medical University.METHODS: Following sacrifice for brain harvesting under anesthesia, the hippocempus was taken to preparation of 400 μ mol/L brain slices. Using extracellular field potential recordings, low-frequency stimulation was performed in the medial molecular layer of dentate gyrus with insulated bipolar tungsten electrodes. After having stable recordings, LTP was induced under high-frequency tetanic stimulation. LTP was induced with a protocol developed previously (4 trains, 500 ms each, 100 Hz within the train, repeated every 20 s). Only those slices which produced the field excitatory postsynaptic potential of 1 mV or cerebrospinal fluid (ACSF)-induced LTP (ACSF-LTP): brain slices were divided into 2 groups: ACSF group, in which, slices were continuously perfused using ACSF bubbled with 95% O2 and 5% CO2; ACSF+ Ro25-6981 group: a 10-minute treatment with 3μ mol/L Ro25-6981 was performed prior to tetanic stimulation, and the remaining procedures were the same as ACSF divided into 2 groups: BIC group: a 10-minute treatment with 10 μmol/L BIC was performed prior to titanic stimulation; BIC+Ro25-6981 group: 3μ mol/L Ro25-6981 and 10μ mol/L BIC were simultaneously perfused 10 minutes prior to tetanic stimulation.MAIN OUTCOME MEASURES: LTP recording results.minutes of titanic stimulation, LTP was (164.67±2.40)% and (147.56±6.63)% in the BIC and BIC+ Ro25-6981 groups,respectively, and a significant difference existed between the two groups (P ＜ 0.05).
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Shenqi-wan, Oriental herbal medicine formulation, has been traditionally used for delayed mental and physical development in children, complications of diabetes, and glomerulonephritis. In the present study, the protective effect of the aqueous extract of Shenqi-wan against traumatic brain injury (TBI) in the rat hippocampal dentate gyrus was investigated. For this study, step-down avoidance task, terminal deoxynuclotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, Bax immunohistochemistry, and 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry were conducted. In the present results, it was shown that apoptotic cell death and cell proliferation in the dentate gyrus were significantly increased following TBI in rats and that the aqueous extract of Shenqi-wan suppressed the TBI-induced increase in apoptosis and cell proliferation in the dentate gyrus. Based on the present results, it is possible that the aqueous extract of Shenqi-wan has a neuroprotective effect on TBI-induced neuronal cell death.