Methylmercury (MeHg) poisoning can lead to Minamata disease, often manifesting as motor dysfunction. We aimed to establish a quantitative evaluation method for MeHg exposure-associated motor dysfunction in the common marmoset (Callithrix jacchus). Three male marmosets were orally administered MeHg (1.5 mg Hg/kg/day) for 2 weeks, followed by a 2-week non-treatment period; three control marmosets received vehicle. Walking and spontaneous behavior were recorded weekly. After marking body segments, bounding gait videos were analyzed to assess locomotion speed, hip joint position, knee angle, dorsal neck-to-torso angle, and spontaneous behavior. In Hg-1 (MeHg-exposed marmoset with earliest symptom onset), locomotion speed and stride length decreased, while stride time increased. In Hg-2 (second marmoset to exhibit symptom onset), hip joint position and knee angle initially showed relatively normal fluctuations during bounding gait. However, their lower limits decreased following MeHg administration, and the dorsal neck-to-torso angle shifted from negative to positive. Spontaneous activity of Hg-1 and Hg-2 significantly decreased after MeHg administration. These results indicate that MeHg exposure-associated motor dysfunction in marmosets can be detected using our method, with particularly prominent lower-limb abnormalities. Furthermore, cerebrospinal fluid proteomic profiling revealed coordinated disruptions converging on three pathological axes—neuronal injury and neuroprotective responses, neuronal metabolic failure and cytosolic enzyme leakage, and impaired transport and homeostatic regulation—identifying nine proteins as candidate biomarkers. Proteomic alterations were consistent with the observed neuronal injury, neuroinflammation, metabolic dysfunction, and impaired homeostatic regulation in affected motor pathways. These findings establish the marmoset as a translational primate model for neurotoxicological assessments and biomarker discovery.
Paclitaxel (PTX) is an effective antineoplastic agent used against various types of cancer. However, its use is limited in many patients due to intolerable side effects, including neurotoxicity. This study examined the effects of aerobic interval training and/or hesperidin (HES) on neuroinflammation and memory impairment caused by PTX in rats. Thirty male Wistar rats were randomly divided into five groups: Sham (SH), PTX, PTX + exercise (EX), PTX + HES, and PTX + EX + HES. To induce PTX toxicity, 2 mg/kg of PTX was injected intraperitoneally into the rats on days 1, 3, 5, 7, and 9. The aerobic exercise program involved five treadmill interval training sessions per week for seven weeks, with each session consisting of 2-minute running intervals. In the first week, the rats completed six repetitions, increasing by one each week until reaching 12 in the final week. Exercise intensity gradually increased from 60
Methamphetamine (MA) is a widely abused psychostimulant known to affect monoaminergic systems, with neurotoxic effects often associated with oxidative stress. The present study investigated the early effects of repeated neonatal MA exposure on dopamine (DA), noradrenaline (NA), and selected markers of oxidative status in the hippocampus and striatum of male rats. MA (5 mg/kg/day, s.c.; PND 1–12) significantly reduced DA levels in both brain regions on PND 12, while lipid peroxidation (TBARS) and antioxidant capacity remained unchanged. By PND 28, the early reduction in DA was no longer detectable, and neonatal MA exposure did not significantly affect body weight within either exposure paradigm. In the indirect-exposure paradigm, post-weaning isolation was associated with increased noradrenaline concentrations, whereas no corresponding housing effect was detected in the direct-injection paradigm; however, treatment × housing interactions were not significantThese findings indicate that early postnatal MA exposure induces transient alterations in dopaminergic neurotransmission without detectable changes in markers of lipid peroxidation, suggesting a normalization of DA levels during early adolescence. Overall, under the present experimental conditions, lipid peroxidation does not appear to be a major contributing mechanism to the observed neurochemical changes.
Neuroprotective effects of statins in Parkinson’s disease (PD) remain uncertain, and their activity in genetic α-synuclein (αSyn) disease models has been insufficiently characterized. We evaluated atorvastatin (ATO) in a mouse model with nigral overexpression of human A53T-mutant αSyn. Mice received ATO by oral gavage at 10 mg/kg/day for 5 weeks and were assessed using behavioral testing, neuropathological assessment, brain transcriptomics, and molecular docking. ATO inhibited cholesterol biosynthesis-related transcriptional programs and broadly remodeled lipid metabolism-associated networks, but did not lead to functional or histopathological benefit. ATO did not ameliorate motor deficits, restore dopaminergic markers, or reduce αSyn protein levels or pSer129-αSyn immunoreactivity. Transcriptomic analysis further showed that ATO failed to reverse the core disease-associated signature induced by A53T αSyn overexpression and instead increased SNCA mRNA. Targeted RNA-seq and western blot analyses showed no parallel increase in Prkn, Gba1, or Lamp2 transcript abundance or in PARKIN, GBA1, or LAMP2A protein expression. Molecular docking, used here as an exploratory structural comparison, suggested a relatively weak predicted interaction between ATO and αSyn when compared with several other statins and provided supportive context for the lack of efficacy. Overall, our findings indicate limited efficacy of ATO in this αSyn-driven setting and support further comparative evaluation of individual statins across complementary PD models.
Sevoflurane (SEV) is widely used in clinical anesthesia, but its exposure is increasingly being linked to neurocognitive dysfunction, particularly in hippocampal neurons. TRIM14, an E3 ubiquitin ligase, is essential for regulating inflammation, apoptosis, and mitochondrial function; however, its involvement in SEV-induced neuronal damage remains unclear. In this study, we investigated the role of TRIM14 in SEV-induced hippocampal neuronal damage, focusing on mitochondrial dysfunction, iron homeostasis, and inflammation. The results show that TRIM14 knockdown significantly increased cell viability, restrained apoptosis, and suppressed inflammatory cytokines in SEV-treated neurons. However, it also alleviated mitochondrial dysfunction, mitigated ferroptosis, and regulated iron homeostasis. Furthermore, silencing TRIM14 suppressed the NF-κB and STAT3 axis. These findings suggest that TRIM14 contributes to SEV-induced neuronal damage.
