Search Results (226)

Mushroom use dates back to ancient times, and it currently remains significant among indigenous and urban populations as a medicinal option. Psilocybe species are suggested to modify emotions when administered in macro- or microdose form for the treatment of anxiety and depression, both often affected by a delayed onset and adverse effects of current pharmacological therapy. The objective of this study was to evaluate the anxiolytic and/or antidepressant-like effects of P. cubensis mushroom aqueous extract (PcAE) microdosing in mice using open-field and rota-rod tests, followed by plus-maze or forced swimming tests. We also evaluated changes in neuronal activity and dendritic maturation using electrocorticography (ECoG) and immunohistochemical techniques. The outcomes were compared with an effective macrodose of PcAE and antidepressant fluoxetine (FLX). For this study, mice were grouped as follows: (1) vehicle, (2) acute, and (3) repeated (10 days) PcAE microdosing (1 µg/kg); (4) single PcAE macrodose (1 g/kg); and (5) acute and (6) repeated reference drug fluoxetine (FLX, 10 mg/kg).The anxiolytic and antidepressant-like effects using microdosing were similar to those observed with macrodoses of PcAE and FLX; significant dose- and/or time-dependent changes in the ECoG and dendritic maturation of hippocampus neurons were also observed, in addition to altered corticosterone levels. To conclude, P. cubensis mushroom promotes brain effects in mice after micro- and macrodosing, supporting its potential as a therapeutic alternative for mental health. Full article

Background/Objective: This study evaluated the analgesic and anti-inflammatory effects of ambroxol in an experimental model of endometriosis. Methods: Ambroxol was administered at doses of 10, 50, and 100 mg/kg (Abx 10, Abx 50, and Abx 100) by daily gavage for 21 days. A medroxyprogesterone-treated group (Progesterone) was included as a positive control. Pain was assessed using validated behavioral tests, including the Rat Grimace Scale (RGS), the von Frey test, and the rotarod test. Additionally, interleukin-1β (IL-1β) levels and total leukocyte counts were measured in peritoneal lavage fluid. The volumetric reduction in endometriotic implants was evaluated by ultrasonography, while histopathological analysis characterized inflammatory infiltrate and epithelial layer integrity using a standardized scoring system. Results: All ambroxol doses reduced spontaneous pain manifestations throughout the treatment. The mechanical withdrawal threshold significantly increased from the second week onward, and motor quality improved over the course of the study. A significant reduction in IL-1β levels compared with the negative control (Control(−)) was observed on day 21. Abx 50 and Abx 100 significantly reduced implant volumes (48.2% and 56.2%, respectively) and promoted marked disruption of the endometriotic epithelial layer. When compared with Progesterone, higher doses—particularly 100 mg/kg—demonstrated comparable efficacy. Conclusions: Taken together, these pleiotropic effects support the potential for drug repurposing in endometriosis. Full article

Background/Objectives: Fetal alcohol spectrum disorders (FASDs) occur in nearly 5% of children in the United States and have been associated with alterations in neurological functions, neuroanatomical changes, and behavioral deficits encompassing an individual’s lifetime. Alterations in myelination have been reported in both rodent models and humans. The cerebellum is a heavily myelinated brain region, and oligodendrocyte and myelination transcripts have been reported to be altered in the cerebellum following early-life ethanol (EtOH) exposure in a mouse model. In this study, we investigated cerebellar-recruited behaviors in adult female mice that were exposed to EtOH from postnatal day (P) 4 to P9. We investigated whether changes in oligodendrocyte lineage markers were present in adulthood. Methods: C57BL/6J offspring received a total of 5.0 g/kg/day of either ethanol (EtOH) or saline in two separate doses delivered subcutaneously two hours apart from P4 to P9. On P21, offspring were weaned and housed with same-sex littermates throughout the duration of the study. From P60 to P90, females underwent behavioral testing including an open field test (OFT), rotarod, and balance beam. Behavior naïve littermates were euthanized on P105, and cerebella were collected for qPCR to assess oligodendrocyte lineage transcripts. Results: We reported that, following EtOH exposure from P4 to P9, adult female mice had increased ambulatory behaviors in the OFT and subtle changes in behavior in the rotarod and balance beam compared to saline-exposed controls. Despite the behavioral changes observed in adulthood, we found that alterations in oligodendrocyte lineage transcripts present on P10 did not persist into adulthood. Conclusions: Subcutaneous injection of EtOH from P4 to P9 resulted in long-term consequences in locomotor and cerebellar-recruited behaviors in female mice. Full article

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that primarily affects the motor neurons. T cell intracellular antigen 1 (TIA1) is a risk gene for ALS pathogenesis. To elucidate TIA1-mediated disease mechanisms, a mouse model recapitulating clinical and pathological features of ALS is needed. TIA1 mutations are rare in human ALS, and mutations are heterozygous, while this study uses a homozygous TIA1 mutant mouse model to amplify pathogenic effects for experimental tractability. Methods: To explore the mechanisms by which mutant TIA1 causes ALS neurodegeneration, we generated a TIA1 mutant mouse by introducing ALS-causing mutations into the endogenous animal via cytosine base editors. Next, behavioral experiments (open-field and rotarod tests) assessed motor function and analyzed pathologies using morphological assessments. Results: Our TIA1Δ mouse model phenocopies select pivotal features of ALS, including TAR DNA-binding protein 43 (TDP-43) accumulation, motor neuron loss, neuroinflammation in the lumbar spinal cord, and muscle atrophy. Notably, this homozygous mutation design with reduced TIA1 expression differs from human heterozygous TIA1 mutations. Conclusions: This work provides a foundation for understanding the TIA1-ALS relationship and for developing strategies to treat this intractable neurodegenerative disorder. Caution is warranted extrapolating findings to human ALS pathogenesis due to model design differences. Full article

Background. Cannabis and cannabinoids have been investigated for their potential therapeutic effects in Parkinson’s disease, but clinical research findings remain scant and inconsistent. This study provides a systematic overview of peer-reviewed meta-analyses assessing their impact on health outcomes in patients with Parkinson’s disease. Methods. A comprehensive search of PubMed, EMBASE, Web of Science, and Google Scholar (from database inception to April 2025) identified meta-analyses evaluating cannabis-based interventions in Parkinson’s disease. Eligible studies reported pooled estimates of effects on neurological symptoms. The most significant findings from the included studies were summarized and qualitatively analyzed. Results. After screening 975 research items, six meta-analyses of clinical and preclinical studies, primarily randomized controlled trials (RCTs), were included. One meta-analysis of five RCTs demonstrated that pure cannabidiol (CBD) or synthetic tetrahydrocannabinol (THC) significantly improved PD symptoms (SMD = −0.41, p = 0.004). Another meta-analysis combining two RCTs and two non-RCTs reported a significant improvement in the Unified Parkinson’s Disease Rating Scale (UPDRS) total score (MD = −4.19, p = 0.03). With regard to pain management, cannabinoids were found effective in one study. Preclinical meta-analyses in animal models showed notable motor improvements, including enhanced rotarod performance (MD = 31.63 s, p = 0.003) and reduced pole test completion times (MD = −1.51 s, p = 0.028). Conclusions. While meta-analyses of clinical studies suggest some benefits of specific cannabinoid formulations, findings are still uncertain. Preclinical data, however, demonstrate interesting motor improvements. Further well-designed RCTs are warranted to clarify the therapeutic role of cannabis in Parkinson’s disease management. Full article

Peripheral nerve regeneration is most rapid during the early post-injury period but gradually slows over time, often limiting functional recovery. Electrical stimulation (ES) delivered via percutaneous needle electrodes has been shown to modulate the local neural microenvironment and promote axonal regeneration; however, the optimal temporal window and duration of stimulation remain unclear. This study aimed to evaluate the time-dependent effects of needle-based ES on peripheral nerve regeneration in a rat model of sciatic nerve transection, using a well-established silicone nerve conduit as a stable and reproducible non-biodegradable repair model. Female Sprague–Dawley rats underwent sciatic nerve transection and repair. Postoperatively (PO), animals were randomly assigned to control (C) needle insertion or needle-based ES groups, receiving stimulation for either 3 weeks (C-3W-PO and ES-3W-PO, respectively) or 7 weeks (C-7W-PO and ES-7W-PO, respectively). Functional recovery was evaluated using cold plate latency and rotarod performance tests. Electrophysiological assessments included measurements of nerve conduction velocity (NCV), compound muscle action potential amplitude, and muscle action potential (MAP) area. Histomorphometric analysis of regenerated nerve tissue quantified total nerve cross-sectional area, endoneurial space, axon number, and axon density. Retrograde labeling with fluoro-gold (FG) was used to quantify reinnervated motor neurons. Immunohistochemical analyses of calcitonin gene-related peptide (CGRP) and macrophage-associated markers were conducted to assess sensory neuropeptide expression and immune cell infiltration within the regenerated nerve. ES significantly improved both sensory and motor recovery in a duration-dependent manner. Behavioral data showed increased cold pain thresholds and improved motor coordination in ES groups, with the most pronounced functional gains observed in the ES-7W-PO group. Electrophysiological measures revealed higher NCV, amplitude, and MAP area in ES-treated animals, with the most pronounced improvements at 7 weeks. Morphologically, ES enhanced nerve regeneration, as evidenced by increased total and endoneurial areas, axonal counts, and axon density. FG-labeled neuron counts were significantly elevated in ES groups, indicating enhanced motor reinnervation. At 3 weeks, ES induced higher CGRP expression and macrophage density, suggesting transient activation of sensory-associated and pro-regenerative immune responses during the early post-injury phase. These findings demonstrate that ES accelerates peripheral nerve repair in rats and that sustained stimulation across the early regenerative window yields superior structural and functional outcomes. Full article

Parkinson’s disease is the second most common neurodegenerative disease in the world. Natural products can offer a possible option of neuroprotective agents for preventing neurodegenerative diseases. D-Pinitol is a cyclic polyol with anxiolytic and antidepressant effects in acute assays. This work aimed to evaluate the effects of D-Pinitol (10, 50, and 100 mg/kg p.o.) in a chronic reserpine-induced depression model (19 days), using the forced swimming and tail suspension tests in female Balb/c mice, and the neuroprotective effects in an MPTP-induced Parkinsonism model (30 days) in male C57bL/6 mice, using behavioral tests such as wire grip, rotarod, catalepsy, and others. D-Pinitol showed low antidepressant-like effects in the reserpine-induced chronic depression model, compared to amitriptyline (25 mg/kg p.o.). D-Pinitol protected MPTP-treated mice from motor impairment with similar effects to those shown by L-Dopa (25 mg/kg p.o.) as evaluated in different behavioral tests. The inhibition of oxidative stress markers, increase in dopamine levels, and avoidance of apoptosis in neuronal cells were the mechanisms by which D-Pinitol protects MPTP-treated mice from motor impairment. Full article

Peripheral nerve injuries, particularly those involving the sciatic nerve, remain a major clinical challenge due to incomplete functional recovery and the limited translation of preclinical advances into effective therapies. This review synthesizes current evidence on the phase-specific evaluation of sciatic nerve regeneration in preclinical models, integrating behavioral, sensory, electrophysiological, and morphological approaches across the acute, subacute (Wallerian degeneration), early regenerative, and late regenerative phases. By mapping functional readouts onto the underlying biological events of each phase, we highlight how tools such as the Sciatic Functional Index, Beam Walk test, Rotarod test, nerve conduction studies, and nociceptive assays provide complementary and often non-interchangeable information about motor, sensory, and neuromuscular recovery. We further examine emerging therapeutic strategies, including intraoperative electrical stimulation, immunomodulation, platelet-rich plasma, bioengineered scaffolds, conductive and piezoelectric conduits, exosome-based hydrogels, tacrolimus delivery systems, and small molecules, emphasizing the importance of aligning their mechanisms of action with the dynamic microenvironment of peripheral nerve repair. Despite substantial advancements in experimental models, an analysis of publication trends and registries reveals a persistent translational gap, with remarkably few clinical trials relative to the high volume of preclinical studies. To illustrate how mechanistic insights can be complemented by molecular-level characterization, we also present a targeted computational analysis of alpha-lipoic acid (ALA,) including frontier orbital energies, physicochemical descriptors, and docking interactions with IL-6, TGF-β, and a growth-factor receptor—performed solely for this molecule due to its documented structural availability and relevance. By presenting an integrated, phase-specific framework for functional assessment and therapeutic evaluation, this review underscores the need for standardized, biologically aligned methodologies to improve the rigor, comparability, and clinical relevance of future studies in sciatic nerve regeneration. Full article

In this study, the neurorehabilitation potential of combined and isolated intermittent hypercapnia and hypoxia exposure was evaluated following photochemically induced cerebral thrombosis in rats. Particular attention was given to the roles of possible neuroplasticity mechanisms mediated by VEGF and BDNF, as well as the potential of hypercapnic–hypoxic interventions to synergistically amplify the therapeutic effects of pharmacological neuroprotectants during recovery. A total of 50 male Wistar rats were randomly assigned to five equal groups (n = 10 per group), each undergoing a course of respiratory interventions lasting 30 min per day for 15 sessions. The groups included (1) a normobaric hypoxia (PO₂ ≈ 90 mmHg) group, (2) a permissive hypercapnia (PCO₂ ≈ 50 mmHg) group, (3) a combined hypercapnic hypoxia (PO₂ ≈ 90 mmHg, PCO₂ ≈ 50 mmHg) group, (4) a control group, and (5) a sham-operated group. Following the rehabilitation protocol, animals exposed to hypercapnic hypoxia exhibited a two-fold reduction in stroke volume compared with controls, significant improvement in motor coordination (as assessed via the rotarod test), and marked upregulation of VEGF and BDNF expression within the ischemic brain region. Notably, only the HH group showed a decrease in serum neuron-specific enolase (NSE) levels. These findings indicate that hypercapnic hypoxia exerts a possible neurorehabilitative effect after focal ischemic injury, superior to that of isolated hypoxia or hypercapnia. Possible mechanisms underlying this outcome may involve activation of neurotrophic (BDNF) and angiogenic (VEGF) signaling pathways. Full article

Background/Objectives: Non-alcoholic steatohepatitis (NASH) is a progressive liver condition closely associated with gut microbial dysbiosis and hepatic metabolic abnormalities. Poria cocos polysaccharide (PCP), a bioactive component derived from the medicinal fungus Poria cocos, possesses hepatoprotective properties, yet the therapeutic mechanisms of PCP in NASH, particularly those involving microbial and metabolic regulation, remain incompletely elucidated. This study aimed to investigate the effects of PCP on improving NASH and explore its mechanisms related to prebiotic activity. Methods: Mice were induced to develop NASH using a Western diet, followed by PCP intervention for 12 weeks. Hepatic function, including liver enzymes and lipids, glucose metabolism, and liver histopathological changes, was assessed. Fatigue and neurobehavioral alterations were evaluated via rotarod, open field, and tail suspension tests. Hepatic pro-inflammatory cytokines were measured using RT-qPCR. Gut microbiota were analyzed through 16S RNA gene sequencing, and metabolites of liver tissue were analyzed through untargeted metabolomics. Results: PCP decreased blood glucose and hepatic lipid levels in NASH mice, alleviating liver inflammation, ballooning degeneration, and fibrosis. It also improved fatigue-like performance on rotarod test and reduced the hepatic expression of IL-6, IL-1β, TNF-α, and IL-18. Microbiota analysis revealed that PCP restored gut microbial diversity, promoted the growth of beneficial taxa such as Alistipes and Butyricoccaceae_UCG-009, and inhibited harmful bacteria, including Romboutsia ilealis. Liver metabolomics showed that PCP normalized key metabolites like taurocholate and regulated taurine and hypotaurine metabolism, which were correlated with reduced inflammation, fatigue-like performance, and fibrosis. Conclusions: PCP, as a promising edible agent, alleviates hepatic damage, metabolic disorders, and fatigue-like performance on rotarod test in NASH mice, probably by reshaping gut microbiota and modulating hepatic taurine and hypotaurine metabolism. Full article

Background: Despite life-saving newborn screening programs and a life-long galactose-restricted diet, many patients with classic galactosemia continue to develop long-term debilitating neurological deficits, speech dyspraxia, and primary ovarian insufficiency (POI). In an earlier study, we showed that administration of an experimental human GALT mRNA predominantly expressed in the liver of the GalT gene-trapped mouse model augmented the expression of hepatic GALT activity, which reduced build-up of galactose and its toxic metabolites not only in the liver but also in the peripheral tissues. Moreover, we showed that the administration of GALT mRNA in the mutant mice restored whole-body galactose oxidation (WBGO), which is a functional biomarker. Methods: In this pilot study, we extended our proof-of-concept efficacy studies to a disease-relevant phenotype: motor impairment. GalT-KO mice aged 3 and 6 weeks old administered biweekly intravenous injections of 100 µL GALT mRNA at a dose of 2 mg/kg for 2 months. Motor performance was assessed using rotarod testing and composite phenotype scoring, 3 and 9 weeks following the dosing regimen. Results: Preliminary results showed that a biweekly dosing at 2 mg/kg for 2 months improved the motor performance of the animals in rotarod and composite phenotype scoring tests in a short-term experiment. Conclusions: Despite being a small-scale study, our findings suggest that when treated early in life, the experimental GALT mRNA is effective in improving the motor-related phenotypes in GalT-KO mice using the specified dosing regimen. These findings highlight the potential of mRNA-based therapies for mitigating neurological symptoms in Classic galactosemia. Full article

Background/Objectives: The cerebellum is essential for motor coordination and has recently been implicated in sleep-related disorders. However, the neural mechanisms linking sleep disruption to motor dysfunction remain poorly understood. This study aimed to elucidate the roles of the deep cerebellar nuclei (DCN), particularly the lateral nucleus, in motor dysfunction induced by chronic sleep disruption (CSD). Methods: Using a validated mouse model of CSD with periodic sleep fragmentation induced by an orbital shaker during the light phase, we assessed neuronal activation via c-Fos immunostaining and performed chemogenetic manipulation of glutamatergic neurons within the lateral nucleus. Behavioral performance was evaluated using open-field and rotarod tests. Results: CSD selectively increased c-Fos expression in the lateral nucleus, with no significant changes observed in other DCN subregions. Chemogenetic activation or ablation of glutamatergic neurons in the lateral nucleus decreased locomotor activity in the open-field test and shortened latency to fall in the rotarod task. Conversely, chemogenetic inhibition of these neurons attenuated CSD-induced impairments, restoring locomotor performance toward control levels. Conclusions: Our findings provide direct experimental evidence that glutamatergic neurons in the lateral nucleus play a crucial role in mediating CSD-induced motor dysfunction. These results highlight the cerebellar contribution to the interplay between sleep and motor control and identify a potential target for therapeutic intervention in sleep-related motor disorders. Full article

Spastic paraplegia 80 (SPG80), caused by mutations in ubiquitin-associated protein 1 (UBAP1), is a pure form of juvenile-onset hereditary spastic paraplegia (HSP) and leads to progressive motor dysfunction. Despite recent advances in the molecular analyses of HSP, disease-modifying therapy has not been established for HSP including SPG80. In the present study, we evaluated the therapeutic potential of 4-phenylbutyric acid (4-PBA), a chemical chaperone and histone deacetylase inhibitor, in Ubap1 knock-in (KI) mice expressing a disease-associated truncated UBAP1 variant. We found that 4-PBA administration significantly improved the motor performance of KI mice in the rotarod and beam walk tests, with maximal benefits achieved when given during pre- or early-symptomatic stages. Partial efficacy was also observed when treatment began after symptom onset in KI mice. Furthermore, 4-PBA attenuated spinal microglial activation and partially restored microglial morphology, although astrocytic reactivity remained unchanged. These findings support 4-PBA as a candidate therapeutic compound for SPG80 and highlight the potential of proteostasis-targeted interventions in HSPs. Full article

Alcohol misuse can lead to alcohol-related brain damage (ARBD), a condition linked to long-term cognitive impairment and considerable disease burden. The pharmacological characteristics of alpha-lipoic acid (ALA) make it a promising candidate for the treatment of ARBD. In this study, adult male Wistar rats were divided into eight experimental groups. Four groups received a 20% (v/v) ethanol–tap water solution ad libitum for 15 weeks to induce early-stage ARBD, while the remaining received only tap water. After 14 weeks, all groups were administered daily injections for one week with either ALA, rivastigmine, or memantine. Behavioral testing included the step-through passive avoidance and rotarod performance tests. Whole-brain biochemical analyses assessed acetylcholinesterase activity, brain-derived neurotrophic factor, and oxidative stress biomarkers. Brain weight, relative brain weight, and brain histopathological changes were also evaluated. Results showed that, similar to memantine and rivastigmine, ALA improved STL at both 24 h and 8 days and reduced ethanol-induced Purkinje cell damage. It also decreased lipid peroxidation levels by 44%, unlike the reference drugs, and superoxide dismutase activity by 33%, similar to them. No other significant changes were detected. Albeit several limitations, this is the first study comparing ALA with rivastigmine and memantine in this experimental context. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder for which no curative therapies currently exist. Experimental models employing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduce PD features such as striatal dopaminergic dysfunction and motor deficits. Various MPTP dosing regimens are used to screen drug candidates for PD, but their validity is limited because of the predominant use of young male animals. Sex bias is another issue that is underrepresented in PD research, since females are more susceptible to this pathology. Here, we studied the model of bolus administration of MPTP (30 mg/kg) in aged female mice and assessed its sensitivity to the antioxidants fullerene C₆₀ and fullerenol C₆₀(OH)₂₄, given that oxidative stress is a key contributor to PD. Methods: 12-month-old female C57BL/6 mice received fullerene (0.1 mg/kg/day, via diet) or fullerenol (0.15 mg/kg/day, via drinking water). On day 10, mice were injected with MPTP. We studied tremor, piloerection, and behavior in the pole test, rotarod, pole test, and open field. High-performance liquid chromatography (HPLC) was employed to study dopaminergic neurotransmission, and the expression levels of its molecular regulators and nitric oxide synthase (NOS)-related targets were investigated using RT-PCR in the striatum and cortex. Results: MPTP-challenged mice displayed profound impairment in markers of dopaminergic neurotransmission and cellular distress, and showed disrupted motor behavior and vegetative functions. Antioxidant-treated animals that received a bolus injection of MPTP demonstrated partial preservation of tremor response, dopaminergic parameters, and iNOS and nNOS gene expression, although motor performance in the pole test was only modestly improved. Fullerenol appeared more effective in decreasing MPTP-induced neurochemical changes. Conclusions: The applied MPTP model showed its validity in mimicking PD features and was sensitive to low doses of antioxidants, suggesting its usefulness for screening drugs that target oxidative and nitrosative stress. The neuroprotective effects of fullerene-based compounds suggest their potential utility in the treatment of PD. Full article