Stem ceils transplantation is one of the potential therapeutic strategies for Alzheimer's disease (AD). Many animal models following stem cell transplantation showed improvement in memory and cognitive function. However, the pathological changes in AD, such as arnyloid beta deposits, negatively affect the survival and differentiaition of stem cells. Stem cells transfectcd with neprilysin or administration of phenserine could at-tenuate these adverse effects. Genetic modification of stem cell by over expression of neurotrophic factors could attenuate the adverse effects not only on stem cells but also on degenerative neurons. Further investigation on how to overcome the adverse effects of phathological factors in AD on stem cells and maximize the therapeutic effects of stem cells would support the hope for introduction of stem cells transplation into clinical application.

Objective To explore Bcl-2 and Bax gene expression in hippocampus region after cerebral ischemia in rats and the modulation of expression by Nimodipine.Methods The cerebral ischemic model of rat was made by occluding left middle cerebral artery according to Nagasawy and Zea Longa improvement method. The rats in one group were pre-treated with Nimodipine. The expression of Bcl-2 and Bax mRNA were measured by RT-PCR method.Results Both Bcl-2 and Bax mRNA were induced in the hippocampus regions after middle cerebral artery occlusion. The Bcl-2 mRNA level was continuously high. However,the level of Bax mRNA increased gradually at first,reached a peak at 24 h,then decreased slowly.For the rats pretreated with Nimodipine Bcl-2 mRNA was up-regulated and Bax mRNA was down-regulated in the hippocampus at 6 and 24 h after ischemia.Conclusion Calcium antagonist can regulate Bcl-2 and Bax genes expression in the hippocampus region after cerebral ischemia.This study indicates that pharmacological modulation of Bcl-2 family member expression may become a new strategy to interfere with neuronal damage.

Objective To investigate the effects of mobility training on mobility and the mRNA levels of both synaptophysin and growth associated protein 43 (GAP-43) in the region around an infarction in rats with acute cerebral infarction. Methods Models of cerebral infarction were created in 100 rats through middle cerebral artery occlusion. They were then randomly divided into training and control groups. The motor skill of the rats was examined using a beam walking test. The mRNA levels of both synaptophysin and GAP-43 in the region around the infarction were observed at the 1st, 3rd, 7th, 14th and 28th days after model-creation using a semi-quantitive reverse transcrip-tion polymerase chain reaction. Results The rats' mobility scores increased with training, and significant differ-ences were observed between the average scores of the two groups at the 3rd, 7th and 14th days. The scores were higher in the training group. The mRNA levels of both synaptophysin and GAP-43 in the region around the infarction increased significantly from the 1st to the 3rd and 7th days. Synaptophysin mRNA levels were significantly higher in the trained group at each time point, but the levels of GAP-43 mRNA were significantly higher in the trained group only on the 3rd and 7th days. Conclusions Motor skill and the mRNA levels of synaptophysin and GAP-43 in the region around an infarction can be increased by motor skill training, at least in rats with model acute cerebral infarc-tion.

The study was aimed to examine the prevalence of depression in patients with Parkinson's disease (PD) and identify its features. A total of 131 out-patients, diagnosed as having idiopathic PD in accordance with the United Kingdom Parkinson's Disease Society Brain Bank criteria, were interviewed with questionnaire and evaluated by Mini-Mental State Examination (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), Hohen &Yahr staging (H&Y staging) and Hamilton Rating Scale for Depression (HRSD). Patients were divided into three groups in terms of HRSD score: depression group, sub-threshold depression group and non-depression group. The clinical variables and symptom profiles were obtained and compared among the three groups. The results showed that 27 patients (20.6%) fell into the depression group, 71 (54.2%) into the sub-threshold depression group, and 33 (25.2%) into the non-depression group. There were no differences in age, gender or tremor score among the groups (P>0.05). Significant differences were found in duration of PD, UPDRS score, rigidity score and H&Y stage between the sub-threshold depression group (or the depression group) and the non-depression group (P<0.05). Moreover, the clinical variables in the subthreshold depression group had the trend of increasing with the severity of PD and their values were similar to those in the depression group. Anhedonia, feeling of incapability, sleep disturbance, gastrointestinal symptoms and depressive moods were most common in the depression group. And these symptoms also were more common in the other two groups. It is concluded that depression and sub-threshold depression are common in PD and share similar clinical features. Furthermore, subthreshold depression might be the prodrome of depression and may develop into depression as the condition progresses.

BACKGROUND: It is indicated in the study of recent years that gingko biloba extract (EGB) is a kind of natural cleaner of free radical and it protects the body from the damage induced by free radical and improves cerebral circulatory disturbance and neuronal function. But the experimental or clinical study on the effects of EGB on high neural functional activity, like cognition, is relatively lagged.OBJECTIVE: To probe into the function of EGB on high functional activity in central neural system so as to provide the experimental evidence on clinical application of EGB in treatment of cognitive disturbance.DESIGN: Randomized controlled experiment was designed.SETTING: Department of Geriatrics of Psychiatric Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology,Department of Pathophysiology in Tongji Medical College of Huazhong University of Science and Technology and Department of Neurology in Union Hospital affiliated to Jinan Medical College of Huazhong University of Science and Technology.MATERIALS: The experiment was performed in Basic Department of Tongji Medical College of Huazhong University of Science and Technology in June 2002. Forty Wistar rats were employed and randomized into 5groups, named as normal control of aged rats (normal group), model group,EGB 75 mg/kg group, EGB 150 mg/kg group and EGB 500 mg/kg group, 8 rats in each one.METHODS: Scopolamine was used to induce disturbance of learning and memory in aged rats to simulate the model of senile dementia animals. In normal and model groups, physiological saline of same volume was used for gastric perfusion and in every EGB group, EGB of 75, 150 and 500 mg/kg was used for gastric perfusion successively, 50-400 g/time, continuously for 5 days. On the 6th day, water maze and evading-dark-room tests were performed. During the testing, the medical perfusion stopped. The assay methods of behavioral training of learning and memory, such as experiment with water maze and evading-dark-room test, and biochemical assay were used to observe the changes in learning and memory and in acetylcholine (Ach) and protein contents in cerebral hippocampus before and after medication.MAIN OUTCOME MEASURES: ① Time required in maze test of rats in each group. ② Mistakes in maze test of rats in each group. ③ Time required and mistakes in evading-dark-room test of rats in each group. ④Contents of Ach and protein in cerebral hippocampus of rats in each group.RFSULTS: Except that 1 rat was died without definite reason in EGB 150 mg/kg group and 1 rat was escaped in either EGB 75 mg/kg or 500 mg/kg group during gastric perfusion, terminally, 37 rats entered result analysis.① The time required and mistakes in maze test in every EGB group were less remarkably than model group (P＜0.05 or P＜0.01). The time required and mistakes in maze test in model group were higher remarkably than normal group (P＜0.01). ② In learning of passive escaping in evading-darkroom test, the duration of learning for the rats in EGB 500, 150, 75 mg/kg groups was shorter remarkably than that in model group [(156.78±25.97),(172.66±13.56), (198.54±17.12), (208.34±28.56) s, P ＜ 0.05 or P＜0.01].The mistakes of electric shock in EGB 500, 150, 75 mg/kg groups were less remarkably than model group [(3.41±0.26), (6.97±0.35), (7.23±0.62),(8.38±0.92) times, P＜0.01]. The times of electric shock in EGB 500 mg/kg group was less significantly than 150 mg/kg group (P＜0.01) and that in 150 mg/kg was less remarkably than 75 mg/kg group (P＜0.05). ③ Hippocampal Ach content in modeled rats in EGB 500, 150, 75 mg/kg groups was higher than that in model group [(421.89±36.32), (387.45±32.76),(380.17±41.25), (365.28±11.42) μg/g, P＜0.05 or P＜0.01]. Hippocampal Ach content in 500 mg/kg group was higher significantly than 150 and 75 mg/kg groups (P＜0.01). In addition, compared with normal group,protein content in hippocampus in rats with disturbance of learning and memory induced by scopolamine in model group was reduced significantly [(41.75±3.82), (95.13±6.34) mg/kg, P ＜ 0.01]. After administrated with EGB,even though the protein content in hippocampus was increased in experimental rats after modeling, the difference was not significant (P＞0.05).CONCLUSION: EGB improves significantly learning and memory in experimental animal in dose-dependence and increases significantly Ach content in hippocampus.

To explore the relationship between beta-amyloid (A beta) and the pathogenesis of Alzheimer disease (AD), after injection of beta-amyloid into the rat brain, the apoptosis of nerve cells and acetylcholine (Ach) content in rat hippocampus were examined by employing TUNEL technique and base hydroxylamine colorimetry respectively. The influence of age and glucocorticoid on the neurotoxic effect of A beta was also analyzed. A beta peptide could strongly induce the apoptosis of neurons in hippocampus, cortex and striate body (P < 0.05 or P < 0.01). In addition, the senility and glucocorticoid pre-treatment could enhance the toxic effect of A beta (P < 0.05 or P < 0.01). It is concluded that A beta may play an important role in the pathogenesis of Alzheimer disease via its induction of apoptosis of neurons and by decreasing the content of the Ach.
Acetylcholine/metabolism ; Aging ; Alzheimer Disease/etiology ; Amyloid beta-Protein/*toxicity ; Apoptosis/*drug effects ; Dexamethasone/*pharmacology ; Drug Synergism ; Hippocampus/metabolism ; Hippocampus/*pathology ; Injections, Intraventricular ; Neurons/pathology ; Rats, Wistar

Mutations in the parkin gene have recently been identified in familial and isolated patients with early-onset Parkinson disease (PD) and that subregions between exon 2 and 4 of the parkin gene are hot spots of deletive mutations. To study the distribution of deletions in the parkin gene among variant subset patients with PD in China, and to explore the role of parkin gene in the pathogenesis of PD, 63 patients were divided into early onset and later onset groups. Exons 1-12 were amplified by PCR, templated by the genomic DNA of patients, and then the deletion distribution detected by agarose electrophoresis. Four patients were found to be carrier of exon deletions in 63 patients with PD. The location of the deletion was on exon 2 (1 case), exon 3 (2 cases) and exon 4 (1 case). All patients were belong to the group of early onset PD. The results showed that parkin gene deletion on exon 2, exon 3 and exon 4 found in Chinese population contributes partly to early onset PD.
Exons/*genetics ; *Gene Deletion ; Parkinson Disease/*genetics ; Point Mutation ; Ubiquitin-Protein Ligases/*genetics

Neural stem/progenitor cells (NSCs) can spontaneously differentiate into neurons and glial cells in the absence of mitogen fibroblast growth factor-2 (FGF-2) or epidermal growth factor (EGF) in medium and the spontaneous differentiation of NSCs is mediated partially by endogenous ciliary neurotrophic factor (CNTF). This study examined the relationship of FGF-2 and CNTF in the spontaneous differentiation of adult hippocampal progenitor cells (AHPs). AHPs were cultured in the medium containing different concentration of FGF-2 (1-100 ng/mL). Western blotting and immunofluorescence staining were applied to detect the expression of the astrocytic marker GFAP, the neuronal marker Tuj1, the oligodendrocytic marker CNPase and, Nestin, the marker of AHPs. The expression of endogenous CNTF in AHPs at early (passage 4) and late stage (passage 22) was also measured by Western blotting. The results showed that FGF-2 increased the expression of Nestin, dramatically inhibited the expression of GFAP and Tuj1 and slightly suppressed the expression of CNPase. FGF-2 down-regulated the expression of endogenous CNTF in AHPs at both early (passage 4) and late stage (passage 22). These results suggested that FGF-2 could inhibit the spontaneous differentiation of cultured AHPs by negatively regulating the expression of endogenous CNTF in AHPs.

BACKGROUND: Brain-derived neurotrophic factor(BDNF) is a potent dopaminergic neurotrophin. The major pathological change in Parkinson disease(PD) is the degeneration and death of dopaminergic neurons in the substantia nigra pars compacta. There is a possibility that the onset of PD is associated with BDNF genetic polymorphisms.OBJECTIVE: To investigate the relationship between BDNF genetic polymorphisms and sporadic Parkinson disease(SPD) in Chinese population with the expectation of offering some genetic data for the primary rehabilitation and prevention of the disease.DESIGN: Explorative study based on DNA samples of SPD patients as study group and DNA samples of healthy population as control group.SETTING: Neurological Department of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Human Genome Center of Huazhong University of Science and Technology.PARTICIPANTS: Subjects included DNA samples of 85 SPD patients(study group, Han population, living in Huazhong area for a long term) offered by Department of Neurology of Wuhan Union Hospital and DNA samples of health persons(control group, Han population, living in Huazhong area for a long term) offered by Human Genome Center of Huazhong University of Science and Technology.METHODS: The genotype of healthy controls and SPD patients was analyzed with the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP).MAIN OUTCOME MEASURES: Genotypes and alleles of the two polymorphisms: G196A and C270T of the two groups.RESULTS: G/A genotype was dominant in both SPD patients and control group with frequencies of 50.6% and 52.0% respectively. The C/C genotype occurred with the frequency of 100% in both groups. There were no significant differences in genotype and allele frequencies of G196A and C270T between SPD and control group( P ＞ 0. 05).CONCLUSION: No association existed between BDNF genetic polymorphisms and the onset of SPD in Chinese Han population of Huazhong area.

Objective To investigate the efficacy and safety of pramipexole versus fluoxetine in the treatment of depression in Parkinson's disease ( PD). Methods A randomized, clinical trial of pramipexole versus fluoxetine treatment for 12 weeks in 50 patients suffering from combined PD and depression was accomplished. The efficacy and safety assessments of the treatments were performed at different time points. Results For the intent-to-treat (ITT) population, the Hamilton Depression Rating Scale (HAMD) scores decreased progressively in both the pramipexole and the fluoxetine group, and a between-time statistical analysis was significant for both groups. The efficacy proportion of patients who responded to the treatment, as defined by at least a 50% reduction in HAMD score, was 56. 0% in the pramipexole group versus 48. 0% in the fluoxetine group (χ~2 =0. 321, P>0. 05). Similarly, the proportion of patients who recovered, as defined by a final HAMD score ≤8, was 52. 0% in the pramipexole group versus 32. 0% in the fluoxetine group (χ~2 =2. 053, P>0. 05) , but the difference between the two treatments showed no statistical significance. At the endpoint, both the Unified Parkinson's Disease Rating Scale (UPDRS) part Ⅱ and part Ⅲ subscores improved in the pramipexole group, by a mean of 2. 9±3. 7 (t= 2.366, P<0.05) and7.2±5.1 (t=2.654, P< 0.05), respectively, and the latter was significantly different from the change in this variable of the fluoxetine group (P<0. 05). Spearman analysis showed that no relationship between HAMD score and UPDRS Part II or Part III subscore. The findings for the per-protocol (PP) population were consistent with the above results, except that the proportion of patients who recovered in the pramipexole group was significantly larger than that in the fluoxetine group. The adverse events in both groups were mild dizziness, nausea and anorexia. No significant difference was found in the frequencies of the adverse events between the pramipexole and fluoxetine group. Conclusions Pramipexole is effective and safe in the treatment of Chinese PD patients combined with depression.