ABSTRACT
Alcohol-Related Brain Damage (ARBD) manifests predominantly as cognitive impairment and brain atrophy with the hippocampus showing particular vulnerability. Fasudil, a Rho kinase (ROCK) inhibitor, has established neuroprotective properties; however, its impact on alcohol-induced cognitive dysfunction and hippocampal structural damage remains unelucidated. This study probes Fasudil's neuroprotective potential and identifies its mechanism of action in an in vivo context. Male C57BL/6â¯J mice were exposed to 30% (v/v, 6.0â¯g/kg) ethanol by intragastric administration for four weeks. Concurrently, these mice received a co-treatment with Fasudil through intraperitoneal injections at a dosage of 10â¯mg/kg/day. Fasudil was found to mitigate alcohol-induced spatial and recognition memory deficits, which were quantified using Y maze, Morris water maze, and novel object recognition tests. Concurrently, Fasudil attenuated hippocampal structural damage prompted by chronic alcohol exposure. Notably, Fasudil moderated alcohol-induced disassembly of the actin cytoskeleton and microtubules-mechanisms central to the maintenance of hippocampal synaptic integrity. Collectively, our findings indicate that Fasudil partially reverses alcohol-induced cognitive and morphological detriments by modulating cytoskeletal dynamics, offering insights into potential therapeutic strategies for ARBD.
ABSTRACT
Nitrogen (N) deposition in the context of human activities continuously affects the carbon cycle of ecosystems. The effect of N deposition on soil organic carbon is related to the differential responses of different carbon fractions. To investigate the changes in soil organic carbon fraction and its influencing factors in the context of short-term N deposition, four N addition gradients:0 (CK), 1.5 (N1), 3 (N2), and 6 (N3) g·(m2·a)-1 were set up in acacia plantations based on field N addition experiments, and the soil physicochemical properties, microbial biomass, and enzyme activities were measured in June and September. The results showed that:â exogenous N input reduced soil pH, promoted the increase in soluble organic carbon content, and increased soil nitrogen effectiveness. â¡ Short-term N addition significantly reduced soil organic carbon content, and the response of each component of organic carbon to N addition was different. Among them, the content of easily oxidized organic carbon was significantly reduced and reached the lowest value under the N2 treatment, with 54.4% and 48.2% reduction compared with that of the control, respectively, and the content of inert organic carbon increased, although the increase was not significant. Nitrogen addition reduced the soil carbon pool activity and improved the stability of the soil carbon pool. Soil carbon pool activity reached its lowest under the N3 and N2 treatments, with a decrease of 53.3% and 52.80%, respectively, compared to that of the control. â¢Random forest modeling indicated that the soil microbial biomass stoichiometry ratio, microbial biomass carbon, and AP were the key factors driving the changes in soil organic carbon activity under short-term N addition, explaining 65.96% and 66.68% of the changes in oxidizable organic carbon and inert organic carbon, respectively. Structural equation modeling validated the results of the random forest modeling, and soil microbial biomass stoichiometric ratios significantly influenced carbon pool activity. Short-term nitrogen addition changed soil microbial biomass and its stoichiometric ratio in the acacia plantation forest mainly through two pathways, i.e., increasing soil nitrogen effectiveness and promoting soil acidification and inhibiting extracellular carbon hydrolase activity, thus changing the soil carbon fraction ratio and participating in the soil organic carbon cycling process.
