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This pilot study investigated the protective effect of transfecting brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (bcl-2) genes in retinal ganglion cells (RGCs) using in vivo electroporation in an adult rat optic nerve transection model. Sprague-Dawley rats were randomly divided into five groups: BDNF(+)/bcl-2(+), BDNF(+), bcl-2(+), empty plasmid (EP), and no surgery (NS). The plasmids were intravitreally injected and electroporated into the left eye. Seven days later, optic nerve transection was performed in all groups except the NS group. Protein expression was examined using Western blotting, RGC survival was quantified using 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) retrograde labeling, and apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) at multiple time points (7, 14, and 28 d after transfection). A significantly higher number of DiI (+) RGCs and lower number of apoptotic cells were observed in the BDNF(+)/bcl-2(+), BDNF(+), and bcl-2(+) groups compared to those in the EP group at all time points. The number of DiI (+) RGCs in the three treatment groups was significantly lower than that in the NS group. However, there were no significant differences among the three treatment groups. The protective effects of gene transfection tended to be strongest in the BDNF(+)/bcl-2(+) group, followed by the BDNF(+) group and then the bcl-2(+) group. Thus, all gene transfection treatments had a protective effect against the loss of DiI(+) RGCs induced by optic nerve transection but did not result in full recovery. This study also confirmed the value of in vivo electroporation. The findings of this pilot study provide a working base for the development of gene therapy for blinding optic nerve disorders. Show less

The aim of the current study was to assess the potential neuroprotective effects of lithium chloride (LiCl) against retinal degeneration (RD) induced by N-methyl-N-nitrosourea (MNU) in the rats. 108 rats were assigned to 6 groups: Control, MNU (80 mg/kg), MNU + 30 mg/kg LiCI, MNU + 60 mg/kg LiCI, 30 mg/kg LiCI, and 60 mg/kg LiCI. The experimental groups comprised 18 rats each and the animals were euthanised on the 2nd, 7th and 14th days following the administration of MNU. Compared with the MNU group, both doses of LiCl significantly reduced retinal cell apoptosis and increased retinal thickness (P < 0.05). MNU group had a higher apoptotic index than the treatment groups, as evidenced by increased immunoreactivities of caspase-3, caspase-6, Bax, and 8-OHdG and decreased immunoreactivities of Bcl-2 at day 2. The outer nuclear layer (ONL) of the retina in rats treated with MNU exhibited a significant reduction in comparison the control group on both days 7 and 14 (P < 0.05). In contrast to the MNU-treated figgroup, the LiCl-injected rats exhibited a notable elevation in the expression levels of BDNF and Bcl-2 (P < 0.05). Conversely, the MNU-treated group exhibited markedly increased expression of GSK-3β, Bax, 8-OHdG, caspase-3, and caspase 6 (P < 0.05). In conclusion, LiCl demonstrated dose-dependent neuroprotective effects against MNU-induced RD in rats. These effects included a reduction in retinal cell apoptosis, an improvement in retinal thickness, and the potential involvement of anti-apoptotic mechanisms, glial activation inhibition, and neurotrophic factor modulation. Show less

The gut microbiota plays a pivotal role in maintaining host health and has increasingly been linked to the pathogenesis of neurodegenerative diseases through the microbiota-gut-brain axis. Parkinson's disease (PD), characterized by dopaminergic dysfunction, neuro inflammation, and pathological alpha-synuclein (α-synuclein) aggregation, is frequently accompanied by gut microbial dysbiosis. Probiotics isolated from human infants could offer distinct neuroprotective and immunomodulatory benefits, yet their effects on integrated gut-brain axis models remain underexplored. In this study, we investigated the therapeutic potential of Lactobacillus acidophilus SLAM_LAA02 (L. acidophilus SLAM_LAA02), a novel infant-derived strain, in modulating PD-related behavioral and neuropathological features via modulation of the gut-brain axis. Following comprehensive safety and functional assessments, we first assessed L. acidophilus SLAM_LAA02 in Caenorhabditis elegans, where supplementation extended lifespan, enhanced antimicrobial defense, improved behavioral responses, and reduced α-synuclein expression in transgenic worms. We then evaluated its effects in a rotenone-induced mouse model that reflects early-stage PD-like features. L. acidophilus SLAM_LAA02 administration ameliorated motor dysfunction, modulated neuroinflammatory signaling, restored gut microbial diversity, and improved intestinal barrier-associated outcomes. These changes were accompanied by a notable reduction in α-synuclein expression and upregulated neuroprotective gene expression, including brain-derived neurotrophic factor (BDNF). Together, these findings suggest that L. acidophilus SLAM_LAA02 exhibits neuroprotective and gut-modulating properties across complementary model systems, supporting its potential as a promising probiotic candidate for alleviating early PD-related dysfunctions through the gut-brain axis. Show less

Nicotine pouches are rapidly increasing in popularity, yet their long-term neurological consequences remain poorly understood. Emerging evidence suggests nicotine may influence seizure susceptibility and neuroimmune signaling, while cannabidiol (CBD) has demonstrated neuroprotective and anti-inflammatory effects. This study investigated the time-dependent impact of acute versus chronic oral nicotine exposure on seizure vulnerability, neuroinflammation, and glymphatic function, and evaluated whether inhaled CBD can reverse these pathological changes. Mice were exposed to acute or 7-day chronic nicotine pouch prior to kainic acid-induced seizures. Seizure severity was scored using the Racine scale. Neuroinflammatory markers (IL-6, HMGB1), neuronal activation markers (BDNF, c-FOS), and Aquaporin-4 (AQP4) expression were quantified via flow cytometry, immunofluorescence, and western blotting. Glymphatic function was assessed using cisterna magna injection of rhodamine dextran tracers. An ex vivo IL-6 modulation assay evaluated nicotine-induced cytokine production and CBD-mediated suppression, with or without IL-6 receptor blockade. Acute nicotine transiently reduced seizure severity, whereas chronic exposure significantly exacerbated seizures, elevated IL-6, HMGB1, BDNF, and c-FOS, and markedly downregulated AQP4. CSF tracer studies confirmed impaired glymphatic influx following chronic nicotine exposure. CBD inhalation effectively reversed seizure severity restored AQP4 expression, normalized IL-6 and HMGB1 levels, and reduced c-FOS protein expression. The IL-6R blockade assay showed that nicotine induces IL-6 production in brain-derived immune cells, while CBD suppresses this response upstream of IL-6 signaling. Chronic nicotine pouch exposure promotes seizure susceptibility through converging neuroimmune and glymphatic disruptions. Inhaled CBD counteracts these effects, supporting its potential as a targeted therapeutic strategy for nicotine-associated neurological risk. This study provides the first evidence that chronic nicotine pouch exposure disrupts glymphatic function, amplifies neuroinflammation, and increases seizure susceptibility through an IL-6-centered neuroimmune network. These findings challenge the perception of nicotine pouches as low-risk products and highlight previously unrecognized neurological vulnerabilities associated with long-term use. The ability of inhaled CBD to reverse these pathological effects identifies a promising therapeutic strategy and underscores the need for further investigation into neuroimmune-glymphatic interactions in nicotine-related brain health. Show less

Growing evidence suggests that resveratrol possesses neuroprotective properties against arsenic toxicity. This study investigated whether resveratrol could ameliorate arsenic-induced depression-like behaviors in male Naval Medical Research Institute (NMRI) mice and explored potential molecular mechanisms. Mice were exposed to arsenic (50 mg/L in drinking water) for 4 weeks and treated with resveratrol (10 or 20 mg/kg). Behavioral assessments included the hole-board test (HBT) for exploratory behavior, and the sucrose splash test (SST), tail suspension test (TST), and forced swim test (FST) for depression-like behaviors. The mRNA levels of Bdnf, Creb1, and Dvl1 in the brain were analyzed by qRT-PCR. Arsenic exposure induced significant depression-like behaviors, characterized by decreased grooming in SST and increased immobility in TST and FST. Resveratrol treatment prevented these behavioral alterations and exhibited intrinsic antidepressant effects in naïve mice, with dose-dependent reductions in immobility time (FST) and increased grooming (SST). Notably, resveratrol (20 mg/kg) enhanced rearing frequency in naïve mice and decreased it in the arsenic-treated mice. At the molecular level, arsenic downregulated Bdnf expression, while resveratrol restored its levels. In contrast, no significant changes in Creb1 and Dvl1 expression were observed. These findings indicate that resveratrol mitigates arsenic-induced depression-like behaviors primarily through the modulation of Bdnf-dependent pathways, independent of Creb1 and Dvl1. These results position resveratrol as a potential antidepressant and underscore its therapeutic promise for mood disorders associated with environmental toxicant exposure. Show less

Pathological neuroinflammation is a critical factor that disrupts neuronal activity and, when sustained, ultimately contributes to neuronal death. Among the primary mediators of neuroinflammation, microglia play a central role in modulating brain immunity. However, their overactivation is closely associated with neuronal damage and structural remodeling of brain tissue, leading to the onset and progression of various neurodegenerative diseases. We investigated the neuroprotective effects of avarol, a marine-derived sesquiterpenoid, focusing on its ability to inhibit lipopolysaccharide (LPS)-induced overactivation of BV2 microglial cells and its subsequent impact on neuronal activity in HT-22 hippocampal neuronal cells. Pretreatment with avarol significantly attenuated the LPS-induced release of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), as well as oxidative stress markers such as reactive oxygen species (ROS) and nitric oxide (NO). These inhibitory effects were further substantiated by a dose-dependent reduction in nuclear translocation of nuclear factor-kappa B (NF-κB), a key transcription factor involved in the inflammatory signaling cascade. Regarding the interaction between microglia and neurons, both conditioned medium and co-culture systems demonstrated that avarol significantly attenuated alterations in neuronal plasticity-related molecules-such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)-induced by activated microglia. Overall, these findings suggest that avarol exerts neuroprotective effects through the modulation of microglia-mediated neuroinflammation. Importantly, avarol's capacity to traverse the blood-brain barrier highlights its potential as an effective pharmacological agent in mitigating neuroinflammation-associated neurological disorders. Show less

Aim: To summarise current knowledge on the effects of intermittent fasting on cognitive functions and neuroprotective mechanisms, with particular attention to Alzheimer's disease and Parkinson's disease. Materials and Methods: A narrative review based on twelve peer-reviewed publications on the effects of intermittent fasting on cognitive function, neuroprotection, and circadian rhythms. Preclinical data and selected clinical studies indicate that intermittent fasting improves memory, attention, and executive functions, which is associated with activation of autophagy, reduction of oxidative stress, improved mitochondrial function, and increased levels of brain-derived neurotrophic factor. In Parkinson's disease, intermittent fasting limits alpha-synuclein aggregation and protects dopaminergic neurons, whereas in Alzheimer's disease it reduces beta-amyloid deposition and enhances synaptic plasticity. Intermittent fasting also influences the gut-brain axis and circadian rhythm alignment, which may further support neuroprotection. Conclusions: Intermittent fasting is a promising adjunct strategy in the management of neurodegenerative diseases. However, well-designed, randomised clinical trials are needed to confirm its effectiveness and safety. Show less