Caffeine intake and anxiety: a meta-analysis.

The results from studies on relationship between caffeine intake and risk of anxiety remains controversial, so we conducted a meta-analysis to summarize the evidence about the association between caffeine intake and risk of anxiety. Relevant articles were identified by researching PubMed, Web of Science, Cochrane library, Embase, CNKI, WANFANG DATA, SinoMed and VIP from the inception to December, 2022. Three investigators independently sifted through the literature, extracted the data, and evaluated the quality of the included studies based on predetermined selection criteria and assessed articles with Risk of bias assessment tool for Cochrane systematic reviews and analytical cross-sectional study quality assessment tool from JBI PACES. After assessing the quality of the literature, meta-analysis was performed using Revman 5.4 and Stata 12.0. Data were obtained from eight articles, and 546 participants from 14 studies in eight articles from healthy populations were included in the caffeine-anxiety analyses. As the scales used to assess anxiety vary in the literature, we chose standardized mean difference as the outcome indicator. In terms of overall effect, the results of the meta-analysis showed that caffeine intake increased the risk of anxiety [SMD = 0.94, 95% Cl = (0.28, 1.60), p < 0.05]. After suspecting that dose size might be responsible for the heterogeneity by sensitivity analysis, we performed subgroup analysis according to dose size and found that low-dose caffeine intake moderately increased the risk of anxiety [SMD = 0.61, 95%Cl = (0.42, 0.79), p < 0.05], whereas high-dose caffeine intake had a highly significant increase in the risk of anxiety [SMD = 2.86, 95%Cl = (2.50, 3.22), p < 0.05]. The results confirm that caffeine intake is associated with an elevated risk of anxiety in healthy individuals without psychiatric disorders, especially when the intake dose is greater than 400 mg.

Mitochondrial transplantation ameliorates hippocampal damage following status epilepticus.

BACKGROUND: Hippocampal damage caused by status epilepticus (SE) can bring about cognitive decline and emotional disorders, which are common clinical comorbidities in patients with epilepsy. It is therefore imperative to develop a novel therapeutic strategy for protecting hippocampal damage after SE. Mitochondrial dysfunction is one of contributing factors in epilepsy. Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria, we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE. METHODS: Pilocarpine was used to induced SE in mice. SE-generated cognitive decline and emotional disorders were determined using novel object recognition, the tail suspension test, and the open field test. SE-induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes. The metabolites underlying mitochondrial transplantation were determined using metabonomics. RESULTS: The results showed that peripheral administration of isolated mitochondria could improve cognitive deficits and depressive and anxiety-like behaviors. Exogenous mitochondria blunted the production of reactive oxygen species, proliferation of microglia and astrocytes, and loss of neurons in the hippocampus. The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism. Among potential affected metabolites, mitochondrial transplantation decreased levels of sphingolipid (d18:1/18:0) and methylmalonic acid, and elevated levels of D-fructose-1,6-bisphosphate. CONCLUSION: To the best of our knowledge, these findings provide the first direct experimental evidence that artificial mitochondrial transplantation is capable of ameliorating hippocampal damage following SE. These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy-associated psychiatric and cognitive disorders.

SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor.

Memory impairment and emotional disorder are two common clinical comorbidities in patients with epilepsy. It is imperative to develop a novel therapeutic agent or a strategy. 6-Chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) is a dopamine-1 receptor agonist and sigma-1 receptor allosteric modulator, which displays the neuron-protective and anti-neuroinflammation activity. We examined the effect of SKF83959 on the memory impairment and emotional disorder in the latent period of epilepsy using the mice post-status epilepticus model. We found that SKF83959 ameliorated memory impairment and depressive-like mood, alleviated the neuron damage and the formation of gliosis in hippocampus, suppressed the rise of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß, and induced nitric oxide synthase in the latent period of epilepsy. Additionally, SKF83959 significantly inhibited the activity of calcineurin and glycogen synthase kinase-3ß. All of these protective actions were reversed by BD1047 (a sigma-1 receptor antagonist). In addition, the intra-hippocampus injection of ketoconazole (a dehydroepiandrosterone synthesis inhibitor) also reversed the protective activity of SKF83959. Thus, we concluded that SKF83959 ameliorated the memory impairment and depressive-like mood in epilepsy via allosterically activating the sigma-1 receptor and subsequently inhibiting the calcineurin/glycogen synthase kinase-3ß pathway.