[Expression of HSP27 in CA1 area of hippocampus in temporal lobe epilepsy model].

OBJECTIVE: To explore the expression of heat shock protein 27 (HSP27) in the CA1 area of hippocampus in temporal lobe epilepsy (TLE) so as to elucidate the relationship between HSP27 and epileptogenesis of TLE. METHODS: The model of TLE was induced by lithium-pilocarpine in the experiment group. And the rats were further divided into the STLE and non-STLE groups based upon the absence or presence of recurrent spontaneous seizure in the next 30 days. Total protein fractions from CA1 area of hippocampus were successively obtained through tissue homogenates abstraction. The HSP27 expression in the CA1 area of hippocamp from three groups was semi-quantitatively analyzed by Western blot. And the expression of HSP27 in CA1 area was detected by pre-embedding immunogold electron microscopy. RESULTS: Expression of HSP27 in the hippocampus CA1 area as detected by Western blot was in accord with that by immunogold electron microscopy. Relative optical density values were 0.912 ± 0.011, 0.431 ± 0.011 and 0.428 ± 0.010 respectively. And gold particles were 50.0 ± 4.2, 23.0 ± 2.8 and 20.0 ± 2.3 respectively. The expression of HSP27 was the highest in the hippocampus CA1 area of the STLE group. There was statistical significance as compared with the non-STLE and normal groups (P = 0.0001). The non-STLE group was higher than the normal group. But there was no significant difference as compared with the normal group (P = 0.63). CONCLUSIONS: HSP27 in the hippocampus CA1 area may participate in the epileptogenesis of TLE.

Potential use of glutathione as a treatment for Parkinson's disease.

The aim of the present study was to assess the efficacy and safety of glutathione (GSH) for the treatment of Parkinson's disease (PD). The PubMed, Cochrane Library, OvidSP, Web of Science, China Science and Technology Journal Database, Chinese National Knowledge Infrastructure and China Wanfang Standards Database databases were systematically searched from the inception dates to October 1st, 2019, using the key words'glutathione' or 'GSH' and 'Parkinson' or 'Parkinson's disease' or 'PD'. The quality of the included articles was assessed using the bias risk assessment tool of the Cochrane systematic evaluator manual (version 5.1.0). Pooled analysis of the relevant data was performed using RevMan 5.3 software and subgroup analysis was performed to determine the impact of the dosage (300 vs. 600 mg) on the outcome measures. A total of seven randomized controlled trials involving 450 participants were included in the meta-analysis. The results of the present study indicated a statistically significant difference between the GSH and control groups, in terms of the Unified Parkinson's Disease Rating Scale (UPDRS) III [standard mean difference (SMD), -0.48; 95% CI, -(0.88-0.08); P=0.02] and GSH peroxidase (SMD, 1.88; 95% CI, 0.52-3.24; P=0.007). However, the differences in the UPDRS I (SMD, -0.04; 95% CI, -0.25-0.16; P=0.70) and UPDRS II (SMD, 0.03; 95% CI, -0.17-0.24; P=0.77) score and in side effects were not statistically significant between the groups. Subgroup analyses revealed that the dosage (300 vs. 600 mg) was an influencing factor for UPDRS III. The present study demonstrated that GSH may mildly improve motor scores in PD, but not at the expense of increased adverse events.

Enriched environment enhances histone acetylation of NMDA receptor in the hippocampus and improves cognitive dysfunction in aged mice.

The mechanisms of age-associated memory impairment may be associated with glutamate receptor function and chromatin modification. To observe the effect of an enriched environment on the cognitive function of mice with age-associated memory impairment, 3-month-old C57BL/6 male mice ("young" mice) were raised in a standard environment, while 24-month-old C57BL/6 male mice with memory impairment ("age-associated memory impairment" mice) were raised in either a standard environment or an enriched environment. The enriched environment included a variety of stimuli involving movement and sensation. A water maze test was then used to measure cognitive function in the mice. Furthermore, quantitative real-time polymerase chain reaction and western blot assays were used to detect right hippocampal GluN2B mRNA as well as protein expression of GluN2B and CREB binding protein in all mice. In addition, chromatin immunoprecipitation was used to measure the extent of histone acetylation of the hippocampal GluN2B gene promoters. Compared with the young mice, the water maze performance of age-associated memory impairment mice in the standard environment was significantly decreased. In addition, there were significantly lower levels of total histone acetylation and expression of CREB binding protein in the hippocampus of age-associated memory impairment mice in the standard environment compared with the young mice. There were also significantly lower levels of histone acetylation, protein expression, and mRNA expression of GluN2B in the hippocampus of these mice. In contrast, in the age-associated memory impairment mice with the enriched environment intervention, the water maze performance and molecular biological indexes were significantly improved. These data confirm that an enriched environment can improve cognitive dysfunction in age-associated memory impairment mice, and suggest that the mechanisms may be related to the increased expression of CREB binding protein and the increased degree of total histone acetylation in the hippocampus of age-associated memory impairment mice, which may cause the increase of histone acetylation of GluN2B gene promoter and the enhancement of GluN2B mRNA transcription and protein expression in hippocampus. The animal experiment was approved by the Animal Ethics Committee of Yangzhou University, China (approval No. 20170312001) in March 2017.

ESE1 expression correlates with neuronal apoptosis in the hippocampus after cerebral ischemia/reperfusion injury.

Epithelial-specific ETS-1 (ESE1), a member of the ETS transcription factor family, is widely expressed in multiple tissues and performs various functions in inflammation. During neuroinflammation, ESE1 promotes neuronal apoptosis; however, the expression and biological functions of ESE1 remain unclear after cerebral ischemia/reperfusion. We performed in vivo and in vitro experiments to explore the role of ESE1 in cerebral ischemic injury. A modified four vessel occlusion method was used in adult Sprague-Dawley rats. At 6, 12, 24, 48, and 72 hours after model induction, the hippocampus was collected for analysis. Western blot assays and immunohistochemistry showed that the expression of ESE1, phosphorylated p65 and active caspase-3 was significantly up-regulated after ischemia. Double immunofluorescence staining indicated that ESE1 and NeuN were mostly co-located in the hippocampus after ischemia. Furthermore, ESE1 was also co-expressed with active caspase-3. PC12 cells were stimulated with cobalt chloride (CoCl2) to establish a chemical hypoxia model. After ESE1 knockdown by siRNA for 6 hours, cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. The levels of ESE1, phosphorylated p65 and active caspase-3 were also remarkably increased in PC12 cells after CoCl2 stimulation. After ESE1 knockdown, PC12 cell viability was increased after hypoxia. siRNA knockdown of ESE1 decreased the level of p-p65 and active caspase-3 after CoCl2 stimulation. These data reveal that ESE1 levels are elevated in the hippocampus after cerebral ischemia/reperfusion injury. This may play a role in neuronal apoptosis via activation of the nuclear factor-κB pathway.

dl-3-n-Butylphthalide prevents oxidative damage and reduces mitochondrial dysfunction in an MPP(+)-induced cellular model of Parkinson's disease.

The aim of the present study was to explore the neuroprotective effects and mechanisms of action of dl-3-n-butylphthalide (NBP) in a 1-methyl-4-phenylpyridiniumion (MPP(+))-induced cellular model of Parkinson's disease (PD). NBP was extracted from seeds of Apium graveolens Linn. (Chinese celery). MPP(+) treatment of PC12 cells caused reduced viability, formation of reactive oxygen, and disruption of mitochondrial membrane potential. Our results indicated that NBP reduced the cytotoxicity of MPP(+) by suppressing the mitochondrial permeability transition, reducing oxidative stress, and increasing the cellular GSH content. NBP also reduced the accumulation of alpha-synuclein, the main component of Lewy bodies. Given that NBP is safe and currently used in clinical trials for stroke patients, NBP will likely be a promising chemical for the treatment of PD.