The clinical correlation between Alzheimer's disease and epilepsy.

Alzheimer's disease and epilepsy are common nervous system diseases in older adults, and their incidence rates tend to increase with age. Patients with mild cognitive impairment and Alzheimer's disease are more prone to have seizures. In patients older than 65 years, neurodegenerative conditions accounted for ~10% of all late-onset epilepsy cases, most of which are Alzheimer's disease. Epilepsy and seizure can occur in the early and late stages of Alzheimer's disease, leading to functional deterioration and behavioral alterations. Seizures promote amyloid-ß and tau deposits, leading to neurodegenerative processes. Thus, there is a bi-directional association between Alzheimer's disease and epilepsy. Epilepsy is a risk factor for Alzheimer's disease and, in turn, Alzheimer's disease is an independent risk factor for developing epilepsy in old age. Many studies have evaluated the shared pathogenesis and clinical relevance of Alzheimer's disease and epilepsy. In this review, we discuss the clinical associations between Alzheimer's disease and epilepsy, including their incidence, clinical features, and electroencephalogram abnormalities. Clinical studies of the two disorders in recent years are summarized, and new antiepileptic drugs used for treating Alzheimer's disease are reviewed.

Integrative analysis of potential biomarkers and immune cell infiltration in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease in the elderly population. However, there are no reliable diagnostic biomarkers for PD, and the pathogenesis of PD still needs further study. The aim of the current study was to identify potential biomarkers and explore the pathogenesis of PD. METHODS: We conducted an integrative analysis of messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) expression profiles of PD using data from the Gene Expression Omnibus (GEO). The GSE110720, GSE110719 and GSE133347 data sets were selected and analysed. Gene ontology (GO) enrichment and gene set variation analysis (GSVA) were performed for annotation, visualization, and integrated discovery. Protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) networks were constructed, and hub genes were identified. Meanwhile, the immune infiltration analysis of hub genes was analysed. Moreover, receiver operating characteristic (ROC) curves were generated to verify the diagnostic value of the differentially expressed genes (DEGs). Finally, the genes with high area under the curve (AUC) values were verified by human samples. RESULTS: We identified 464 DEGs closely related to PD, including 154 mRNAs, 134 miRNAs, and 176 lncRNAs. The GO analyses indicated that changes in PD were mainly enriched in receptor ligand activity and cytokine receptor binding. The KEGG enrichment analysis showed that these DEGs were significantly involved in cytokine-cytokine receptor interactions, signalling pathways regulating the pluripotency of stem cells and Th17 cell differentiation. GSVA suggested that growth factor binding, IL2-stat5 signalling, and IL6-jak-stat3 signalling were crucial in the development of PD. A total of five hub genes (NPBWR2, CXCL10, CXCL5, S1PR5, and GALR1) were selected via the PPI network. A ceRNA network of the CXCL5, CXCL10 and S1PR5 genes was constructed, and target genes of the three genes were screened. The immune infiltration analysis showed that there were significant differences in a variety of immune cells between the hub genes. The expression of DEGs was validated in clinical human samples by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression levels of hsa-miR6895-5p, hsa-miR6791-5p, hsa-miR518f-5p, hsa-miR455-3p and TEKT4P2 were decreased, while the levels of TPTE2P6 were increased in human samples. These findings are consistent with the bioinformatics analysis results. CONCLUSION: We found that the immune inflammatory response and immune cell regulation were involved in the pathogenesis of PD. Five hub genes involved in the immune infiltration biological processes of PD based on bioinformatics. We verified the DEGs with significant differences by qRT-PCR. These findings might provide new insight into the pathogenesis of PD and the development of diagnostic and therapeutic strategies for PD.

LncRNA AC136007.2 alleviates cerebral ischemic-reperfusion injury by suppressing autophagy.

Differential expression and diagnostic significance of the long noncoding RNA (lncRNA) AC136007.2 has been reported in patients with acute ischemic stroke (AIS). However, its role on disease progression and outcome remains unclear. Here, we employed an oxygen-glucose deprivation/reperfusion (OGD/R) model in neuronal SH-SY5Y cells and performed middle cerebral artery occlusion (MCAO) surgery in rats to investigate the function of AC136007.2 in ischemia-reperfusion (I/R) injury. AC136007.2 expression was determined by RT-qPCR and cell viability was examined using CCK-8, Edu, LDH, and apoptosis assays. Pro-inflammatory cytokine expression was assessed using ELISA. OGD/R downregulated AC136007.2 expression in SH-SY5Y cells, decreased viability by inducing apoptosis, and stimulated secretion of TNF-α, IL-6, and IL-1ß. In turn, lentivirus-mediated AC136007.2 overexpression significantly reversed these phenomena. LC3 immunofluorescence and western blotting analyses of LC3-I/II and Beclin-1 expression and AMPK/mTOR phosphorylation status showed that AC136007.2 suppressed autophagy in SH-SY5Y cells via inactivation of AMPK/mTOR signaling. Notably, incubation with the AMPK activator AICAR abolished the pro-survival effect of AC136007.2 upon OGD/R treatment. Importantly, intraventricular injection of AC136007.2 significantly reduced cerebral infarction and brain edema in MCAO rats, as shown by TTC staining and water content measurements. We conclude that AC136007.2 alleviates cerebral I/R injury by suppressing AMPK/mTOR-dependent autophagy.

NF-κB dependent up-regulation of TRPC6 by Aß in BV-2 microglia cells increases COX-2 expression and contributes to hippocampus neuron damage.

The deposition of amyloid ß-protein (Aß) has been involved in neurodegeneration of Alzheimer's disease (AD). Besides Aß plaques and neuronal loss, microglia activation is also common in AD patient brains, suggesting its important role in the pathogenesis of AD. Although activation of microglia by Aß plaques has been demonstrated, the mechanism underlying it is still largely unclear. Here, we found that TRPC6 has a crucial role in microglia activation by Aß. Aß up-regulates the level of TRPC6 via NF-κB in BV-2 microglia and increases the expression of pro-inflammatory factors and oxidative enzyme, COX-2. Knock-down of TRPC6 reduces the Aß-induced expression of pro-inflammatory factors and COX-2 and the damage of hippocampus neurons. Furthermore, inhibition of COX-2 also protects hippocampus neurons from Aß-induced inflammatory damage. Collectively, our studies suggest that Aß increase the expression of TRPC6 via NF-κB in BV-2 microglia and promotes the production of COX-2, which induces hippocampus neuron damage.

Anti-Inflammatory Effects of Schisandrin B on LPS-Stimulated BV2 Microglia via Activating PPAR-γ.

Schisandrin B (Sch B), a dibenzocyclooctadiene lignan isolated from Schisandra chinensis (Turcz.) Baill, has been shown to have anti-inflammatory effect. The purpose of this study was to evaluate the effect of Sch B on LPS-induced inflammation in microglia and to investigate the molecular targets of Sch B. BV2 cells were stimulated by LPS in the presence or absence of Sch B. The results showed that the levels of TNF-α, IL-6, IL-1ß, and PGE2 upregulated by LPS were significantly suppressed by Sch B. LPS-induced NF-κB activation was also inhibited by Sch B. Furthermore, Sch B was found to upregulate the expression of PPAR-γ in a concentration-dependent manner. In addition, the inhibition of Sch B on TNF-α, IL-6, IL-1ß, and PGE2 production were reversed by PPAR-γ antagonist GW9662. In conclusion, these results suggested that Sch B inhibited LPS-induced inflammatory response by activating PPAR-γ.

The effects and mechanism of estrogen on rats with Parkinson's disease in different age groups.

OBJECTIVE: In order to investigate the effect and mechanism of estrogen in rotenone-induced Parkinson's disease (PD) rats in different age groups. METHODS: we established rat models of PD by rotenone at different interventions. Then, behavioral tests, immunohistochemistry, western blot, high-performance liquid chromatography-electrochemical detector (HPLC-ECD) and electron microscopy were performed. RESULTS: Results revealed the following: (1) Rotenone significantly reduced rotarod latencies in senile rats, prolonged their climbing pole time, and decreased TH positive cells, DA and its metabolite, DOPAC. Estrogen ameliorated this effect, in which weaker effects were observed in younger rats compared with older rats. (2) Rotenone increased the expression of LC3-II in older rats, but estrogen and tamoxifen did not show the same effect. (3) Rotenone increased the number of autophagosomes, but estrogen increased the proportion of autolysosomes/autophagosomes in the rotenone-treated group. (4) U0126 could reduce the number of autophagosomes in the rotenone-treated group, but this did not change the proportion of autolysosome/autophagosome in combining rotenone with the estrogen group. Rapamycin did not increase the number of autophagosomes in the rotenone-treated group, but combining rapamycin with estrogen and rotenone was able to further increase the proportion of autolysome/autophagosomes. Therefore, we speculate that the senile rat model of PD was more reliable than that in young rats. CONCLUSIONS: In addition, estrogen could promote autophagy maturation through the ERK pathway, and had an obvious therapeutic effect on the rat model of PD.