Background The complex pathophysiology of epilepsy hampers the development of effective treatments. Although more than ten kinds of anti-seizures drugs (ASDs) have good effects on seizure control worldwide, about 30% of patients still display pharmacoresistance against ASDs. Neuroinflammation seems to play a crucial role in disease progression. G protein-coupled receptor 120 (GPR120) has been shown to negatively regulate inflammation and apoptosis. However, the role of GPR120 in epilepsy remains unclear. In this study, we aimed to explore the mechanism of GPR120 in epilepsy. Methods Male adult C57BL/6 mice were intracranially injected with kainic acid (KA) to establish epilepsy model, and the adeno associated virus (AAV) was administered intracranially at 3 weeks before KA injection. VX765 was administered by intragastric administration at 30 min before KA induced and an equal dose administrated twice a day (10 a.m. and 4 p.m.) lasting 7 days until the mice were killed. Western blot analysis, immunofluorescence staining, video monitoring of seizure, LFP recording, Nissl staining were performed. Results GPR120 was increased in both the hippocampus and cortex in the KA-induced model with temporal lobe epilepsy (TLE), and both were most highly expressed at 7 days after KA injection. Overexpression of GPR120 significantly alleviated epileptic activity, reduced neuronal death after status epilepticus (SE), downregulated the expression of IL-1β, IL-6, IL-18, and pyrin domain-containing protein 3 (NLRP3) inflammasome, whereas knockdown GPR120 showed the opposite effect. The effects of GPR120 knockdown were reversed by VX765 inhibition cysteinyl aspartate specific proteinase-1 (Caspase-1). Conclusion GPR120 modulates epileptic seizure activity and affects neuronal survival in KA-induced mouse model of temporal lobe epilepsy. Furthermore, GPR120 regulated neuroinflammation in epileptic animals through NLRP3/Caspase-1/IL-1β signaling pathway.

Increasing evidence suggests that changes in the triggering receptor expressed on myeloid cells 2 (TREM2) is closely correlated with the pathological development of Alzheimer's disease (AD). However, the biological function and related role of this change remain poorly understood. Higher TREM2 expression has been reported in the brain of AD patients than in normal controls. Here, levels of TREM2 gene and protein levels were observed to be higher in both cortex and hippocampus of the Aβ1‐42‐induced AD mice than in those of the wild type mice. Together with in vitro experimental data, we found that the anti‐inflammatory role of TREM2 was, to some extent, limited and potentially counteracted by the hyperactive toll‐like receptor 4 (TLR4) in the AD mice. In this context, Interleukin 4 (IL‐4), as an agonist of TREM2, was administered to the AD mice to persistently activate TREM2. Interestingly, TREM2 activation in IL‐4‐treated AD mice led to an elevation in lysosomes and microtubule‐associated protein 1 light chain 3 (LC3) II/I expression, demonstrating that the level of microglia autophagy was increased. Increased autophagy significantly downregulated the expression levels of caspase recruitment domain‐containing protein 9 (CARD9) and TLR4, potentially weakening the CARD9‐TLR4 pathway and suppressing the TLR4‐mediated pro‐inflammatory effect in IL‐4‐treated AD mice. Furthermore, data acquired from Morris water maze testing indicated that IL‐4 administration could ameliorate cognitive impairment in the AD mice. In conclusion, the findings from in vitro and in vivo experiments suggest that TREM2 might represent a potential drug target to treat neuroinflammation in AD.

Background: Malnutrition is one of the health problems in the elderly population, which increases the risk of poor clinical outcomes. The purpose of this investigation was to evaluate the nutritional status and cognitive function of an elderly Chinese population, to explore the association between malnutrition and cognitive condition as well as the cognitive domain.Methods: A cross-sectional study was conducted in 2365 participants aged 60 years or above from January 2013 to September 2019. We used the Mini Nutritional Assessment Short Form (MNA-SF), and the Mini Mental State Examination (MMSE) to assess the impact of malnutrition on cognitive function.Nutrition-associated factors were analyzed.Results: 33.45% of the participants were identified as malnutrition risk and 5.54% were malnourished, while 36.74% had cognitive impairments. 48.63% had nutritional deficits and 53.65% had cognitive impairment in those over 80 years old. Malnutrition is associated with global cognition (ρ= 0.349, P < 0.0001) and the cognitive domain particularly in orientation (ρ= 0.343, P < 0.0001). The impact was extended to attention and calculation (ρ=0.310, P < 0.0001) as well as language (ρ= 0.302, P < 0.0001) of those over 80 years of age. Malnutrition is an independent risk factor for cognitive impairment after adjusting for other variables (OR=2.004, 95% CI: 1.621-2.479).Conclusion: The prevalence of malnutrition and cognitive impairment was relatively high and increased with age. Malnutrition leads to cognitive decline and disorientation, and also contributes to attention problems, calculation problem and language impairment in the oldest old. Thus, clinicians should assess the nutritional and cognitive status of the elderly regularly to the early dictation and timely intervention.

BackgroundEpilepsy is a common neurological disease, and excessive mitophagy is considered as one of the major triggers of epilepsy. Mitophagy is a crucial pathway affecting reactive oxygen species. Phosphoglycerate mutase 5 (PGAM5) is a protein phosphatase present in mitochondria that regulates many biological processes including mitophagy and cell death. However, the mechanism of PGAM5 in epilepsy remains unclear. The purpose of the present study was to examine whether PGAM5 affects epilepsy through PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy.MethodsAfter the knockdown of PGAM5 expression by the adeno-associated virus, an epilepsy model was created by kainic acid. Next, the seizure activity was recorded by local field potentials before evaluating the level of mitochondrial autophagy marker proteins. Lastly, the ultrastructure of mitochondria, neuronal damage and oxidative stress levels were further observed.ResultsA higher PGAM5 level was found in epilepsy, and its cellular localization was in neurons. The interactions between PGAM5 and PINK1 in epilepsy were further found. After the knockdown of PGAM5, the level of PINK1 and light chain 3B was decreased and the expression of the translocase of the inner mitochondrial membrane 23 and translocase of the outer mitochondrial membrane 20 were both increased. Knockdown of PGAM5 also resulted in reduced neuronal damage, decreased malondialdehyde levels, decreased reactive oxygen species production and increased superoxide dismutase activity. In addition, the duration of spontaneous seizure-like events (SLEs), the number of SLEs and the time spent in SLEs were all reduced in the epilepsy model after inhibition of PGAM5 expression.ConclusionInhibition of PGAM5 expression reduces seizures via inhibiting PINK1-mediated mitophagy.

Background There is a lack of research on life expectancy estimation in advanced dementia patients. In this prospective study, we evaluated the usefulness of the advanced dementia prognostic tool (ADEPT) for estimating the 2-year survival of patients in China. Methods Patients were recruited from nursing homes and hospitals in Chongqing, China, and followed up for 2 years. The usefulness of the ADEPT score for predicting the 2-year survival rate was evaluated using the area under the receiver operating characteristic (AUROC) curve. Results In total, 115 patients were included in the study. Of these patients, 48 died. The mean ADEPT score was 13.0. The AUROC for the prediction of the 2-year mortality rate using the ADEPT score was 0.62. The optimal threshold of ADEPT score was 11.2, which had an AUROC of 0.63, specificity of 41.8, and sensitivity of 83.3. Conclusions The ADEPT score based on a threshold of 11.2 was useful to determine the 2-year survival rate of patients with advanced dementia in Chongqing, China. The survival estimation may be used to improve the treatment of patients.