Homocysteine (Hcy) is a non-proteic amino acid that participates in the remethylation cycle of methionine. Hcy levels in plasma around 16-30 µmol/L are characteristics of mild hyperhomocysteinemia (HHcy), which is a know risk factor for neurodegeneration. Given this, Hcy may serve as an early biomarker of cognitive decline. In the present study, we evaluated behavior in different tasks in adult male and female rats submitted to mild HHcy and analyzed markers of blood-brain barrier (BBB) integrity (aquaporin, occludin, and β-catenin), the expression of p- TAU217, inflammatory mediators (IL-6 and IL-10), and key cellular markers (GFAP, AIF1, and RbFOX3) in the hippocampus and cortex of these animals. Results revealed that mild HHcy induced short-term and spatial memory impairment in adult male rats, accompanied by region-specific alterations in the cortex and hippocampus. In males, we also observed that HHcy reduced occludin content, IL-10 and RbFOX3; in the hippocampus, HHcy increased the expression of IL-10 and AIF1. The female rats did not exhibit memory deficits, o the other hand, the expression of p- TAU217, and GFAP were increased in the cortex of these animals. Together our finding drive that mild HHcy may represent a valuable translational model for studying early-stage cognitive decline and tauopathy, particularly in the context of sex-specific vulnerability.

Parkinson's disease (PD) is a progressive neurodegenerative disease thought to arise from the collective impact of advancing age, genetic vulnerabilities and possibly exposure to environmental toxicants. The LRRK2 point mutation, G2019S, is the most common genetic link with PD and has been reported to have age-dependent effects in rodents, as well as being linked to neuroinflammatory processes. Accordingly, the objective of the current study was to elucidate the interactive effects of advanced age and activation of the immune system using the bacterial endotoxin, lipopolysaccharide (LPS), in G2019S knockin mice and their wild type littermates. Adult young (3-4 months) and aged (9-12 months) mice were administered five intraperitoneal injections of 250mg/kg of LPS (or saline) every alternate day. Significant interactions between age, genotype and injection were evident across several behavioral outcomes. In fact, the aged G2019S mice were more vulnerable to the LPS injections in terms of the sickness response, deficits in nest building behaviors, weight loss, along with protracted reductions in home cage motor activity. These mice also exhibited alterations of SNc inflammatory microglia proteins (WAVE2 and CXCR1) and had the greatest loss of substantia nigra dopamine neurons, which is consistent with a PD-like phenotype. Taken together, our data suggest that the LRRK2 G2019S mutation might be a general regulator of aging and inflammatory processes that are important for neurodegeneration, together with motor and non-motor symptoms.

Movement is a critical component of human functionality, influencing daily activities and overall quality of life. For this reason, precise and complete execution of the movements is extremely important. However, traumatic and non-traumatic pathologies can impair neuromuscular and musculoskeletal systems, leading to motor dysfunction. Accurate etiological diagnosis and evidence-based therapeutic strategies are crucial in managing movement disorders, whether through restorative treatment or symptomatic relief. This study investigates the multifactorial pathogenesis of movement disorders and provides a comprehensive review of current therapeutic approaches, including rehabilitation strategies, pharmacological management, surgical interventions, and emerging treatment modalities. The selection of accurate, patient-specific therapeutic interventions enables clinicians to optimize motor function and minimize disability in patients with movement disorders.

In the Mongolian gerbil (Meriones unguiculatus), testosterone (T) and its metabolites estradiol (E) and dihydrotestosterone (DHT) participate in the regulation of paternal behaviour. E activates the oxytocinergic system, comprised of oxytocin (OT) and its receptor (OTR), in maternal behaviour. However, whether T, E and DHT regulate paternal behaviour through the activation of OT/OTR is unknown. The aim of this study was to determine whether these hormones activate the oxytocinergic system as part of the neuroendocrine mechanism in the regulation of paternal behaviour in the Mongolian gerbil through increases in OT and the OTR in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MeA) and olfactory bulb (OB). Fifty males aggressive towards pups were organised into five groups of 10 animals each: bilateral castration + T injection, bilateral castration + E injection, bilateral castration + DHT injection, bilateral castration simulation + vehicle, and bilateral castration. After paternal behaviour tests were performed, blood samples were obtained to quantify T, E, and DHT by ELISA. The brains were removed and analysed for immunoreactivity (ir) of OT and OTR. One hundred percent of the males who received T, E, and DHT injections stopped being aggressive and became paternal. Compared with castrated and sham-castrated males, males that received T, E, and DHT injections presented greater numbers of OT-ir and OTR-ir cells in the mPOA and BNST. These results suggest that the oxytocinergic system could be one of the mechanisms through which T, E, and DHT regulate paternal behaviour.

Flight missions inherently involve dynamically changing task load and cumulative task duration, both of which contribute to the development of mental fatigue in pilots. This study aimed to investigate whether the characteristics of brain microstates, from the perspective of global brain networks, exhibit significant changes in response to mental fatigue and varying task loads. Thirty pilot trainees participated in a 1.5-hour simulated flight consisting of three task loads presented in pseudorandom order. Electroencephalogram (EEG) data were continuously recorded throughout the experiment, and fatigue levels were classified using the Karolinska Sleepiness Scale (KSS) administered at the end of each task segment. The results revealed that the mean duration, occurrence rate, and time coverage of microstate D significantly decreased with the onset of mental fatigue. Additionally, the transition probabilities from microstates C and D to B decreased, while transitions from microstate B to C and D increased. Notably, no statistically significant effects of task load were observed on microstate parameters throughout the entire simulation. These findings suggest that mental fatigue plays a dominant role in modulating brain network microstate dynamics during simulated flight.

This study aimed to investigate the neural correlates of cognitive fusion (CF) in drug-naïve patients with obsessive-compulsive disorder (OCD) and to explore the potential involvement of neurotransmitter systems in these abnormalities.

Chronic neuroinflammation is a key contributor to cognitive decline in neurodegenerative disorders, and improving gut health with probiotics has been proposed as a potential therapeutic strategy. This study investigated the neuroprotective efficacy of Lactobacillus gasseri MG4247 and Lacticaseibacillus rhamnosus MG4644 in a lipopolysaccharide (LPS)-induced mouse model of neuroinflammation-induced cognitive impairment. Compared to mice receiving LPS alone, mice cotreated with LPS and probiotics demonstrated significantly improved spatial memory as measured in the Morris water maze, working memory in the Y-maze, and associative fear learning in the passive avoidance test. These improvements were comparable to LPS model mice cotreated with the clinical acetylcholinesterase inhibitor donepezil. Enzyme-linked immunosorbent assays analysis revealed marked reductions in proinflammatory cytokines (TNF-α, IL-6) in both serum and hippocampus, while histological examination showed reduced neuronal degeneration in the hippocampal CA1 region of LPS model mice cotreated with probiotics. Both probiotics also enhanced gut production of the butyrate, which is known to improve the gut microbial profile and barrier function. Notably, both probiotics also significantly increased brain-derived neurotrophic factor (BDNF) expression and restored phosphorylation of protein kinase B (Akt) and cAMP-response element binding protein (CREB), components of signaling cascade essential for synaptic plasticity, memory formation, and neuronal survival under neuroinflammatory stress. These findings suggest that L. gasseri MG4247 and L. rhamnosus MG4644 mitigate LPS-induced cognitive deficits through anti-inflammatory effects and activation of the Akt/CREB/BDNF pathway. This study supports the potential of probiotics for suppressing neuroinflammation and enhancing cognitive function via neural, immune, and endocrine pathways of the gut-brain axis.

Hypoxia is a major component of ischemic stroke. The prevalence of ischemic stroke is expected to increase as the global population ages and risk factors, like obesity, are on the rise. Nutrition is a modifiable risk factor for ischemic stroke. Increased dietary intake of folic acid (FA) has become an increasing problem in the U.S and other countries as more people are consuming at or above the recommended daily amount of FA. The impact of too much dietary FA on hypoxia is not well understood. This study aimed to investigate how increased dietary levels of FA impact hypoxia outcomes using Drosophila melanogaster as a model. Adult female and male wDrosophila melanogaster flies were placed on control (CD) and 100 µM folic acid (FAD) diets. At 5-6 days old fruit fly progeny were exposed to hypoxia for two hours prior to returning to normoxic conditions. We observed escape behavior in hypoxia larvae, confirming exposure to hypoxia. Using liquid chromatography-tandem mass spectrometry, elevated FA levels were observed in FAD compared to controls. We report increased acute hypoxia-induced mortality in FAD flies. Furthermore, FAD flies were not motivated to climb after hypoxia. Under normoxic conditions FAD flies had a higher velocity when descending during a climb. Interestingly, there was no impact of FA on apoptosis in brain tissue post-hypoxia. Together these data suggest that increase dietary intake of FA can have negative health outcomes after hypoxia.

In altricial mammal species, isolation calls are vocalisations the young produce when they are separated from the mother. While mother/offspring interactions during the postnatal period affect pups' isolation calls rate, the contribution of interactions with other adults in shaping this response remains to be explored. We took advantage of the variation in the composition of the parental environment in the wild in a monogamous species (Mus spicilegus) to investigate how the vocal response of pups during separation could be affected by the number of adults that provide daily care in the nest. Three types of parental environments were studied: monoparental, biparental and polygynous. First, we quantified the parental care received by pups during the first postnatal week in the different parental units. Second, pups' vocal responses to isolation were recorded on postnatal day 9. Pups received less care (licking and handling) in monoparental than in biparental or polygynous units, and no difference was observed between biparental and polygynous units. Pups that emitted higher call rates in response to isolation were the ones which were less often left alone in the nest and which received a larger amount of maternal care.

Neural stem cells (NSCs) showed a promising approach to treat Alzheimer's disease (AD). This study aims to investigate whether mouse NSCs transplantation can improve the function of learning and memory of AD mouse model and the underlying mechanism. NSCs was stereotaxically injected into the hippocampi of ibotenic acid (IBO)-induced AD mice. Behavioral tests were conducted to evaluate neurological function. Golgi and immunofluorescence staining were used to assess the injury of the nerves. Additionally, enhanced green fluorescent protein (EGFP) labeling was employed to evaluate the differentiation of NSCs. Compared with model group, NSCs transplantation shortened the escape latency and increased the crossing platform quadrant time, number of crossing the platform (p < 0.01). The preference index and active avoidance rate was increased after NSCs transplantation when compared with the model group (p < 0.05 or p < 0.01). NSCs augmented not only the number of neurons in the hippocampal CA1 region, but also the dendritic spine density, dendritic complexity and ACh content in the hippocampus (p < 0.05 or p < 0.01). Furthermore, NSCs also elevated the levels of BDNF in the hippocampus of AD mice (p < 0.01). It also showed that a portion of transplanted NSCs differentiated into neurons at four weeks post-transplantation. These results demonstrated that NSCs improved learning and memory function in the AD model by ameliorating neuron injury and differentiating into neurons.

People with visual impairment (VI) may have improved tactile recognition skills due to enhanced cognitive processing. However, whether this enhancement varies depending on whether VI is acquired early or late is unclear. This study aimed to determine the differences in behavioral performance during tactile stimulus detection and P300 wave latency between three groups: early-onset VI group (EVI), late-onset VI group (LVI), and sighted control group (CG). Brain cortical activity was also analyzed. Participants' hands were passively stimulated with a vibrotactile device, and participants were asked to identify the stimulus while electroencephalography and P300 event-related potentials were recorded. Behavioral performance, P300 latency, and bioelectrical brain activity were assessed. EVI (n = 13) and LVI (n = 12) groups showed better tactile recognition performance with shorter reaction times than CG (n = 14) (p < 0.05). This may be due to the tactile experience that people with VI may have. No differences were found among the three groups for P300 latency (p > 0.05). Both EVI and CG groups exhibited significant activity in the superior and middle frontal regions, which may be related to attention and working memory processes. EVI group also exhibited greater activity in bilateral parietal structures, which may be linked to multimodal information processing and the dorsal pathway, involved in spatial processing (the "where" of things). By contrast, the LVI group showed significantly higher activity in the superior temporal areas, which may be related to the ventral pathway responsible for object identification (the "what" of things).

Adjusting posture is crucial for animals. When animals topple over, they attempt to restore their body posture to the default state. In the case of Drosophila larvae, they can restore their posture through self-righting (SR) behavior when placed side-up or ventral-up. However, the mechanisms of muscular regulation underlying SR behavior remains unknown. In this study, we reported that Drosophila larvae achieve postural reorientation through four strategies and their combinations for the first time, while exhibiting strategic bias. Among the four SR strategies, the most frequently used were the asymmetric SR-fwd, followed by the oblique muscle-powered SR-torsion as the second most frequently employed strategy, while SR-bwd and SR-roll exhibit significantly lower utilization frequencies. These findings not only provide a detailed characterization of larval SR behavior and its strategic diversity, but also elucidate critical muscular regulatory mechanisms underlying SR execution and strategy bias modulation. This research offers important implications for motion control system design and biomimetic robotics development, particularly regarding self-posture adjustment mechanisms.

The beetle mania test (BMT) is a novel ethologically relevant behavioral test which measures the behavior of mice in an enclosed arena in the presence of an erratically moving robotic beetle. When the beetle approaches, the mouse may exhibit either passive behavior, disregarding the stimulus, or active defensive responses, such as escape or flight, which are indicative of panic-like reactions. We compared behavior of 4 different mouse strains in the BMT using undirected jumps as an index of panic-like behavior. Male C57BL/6 mice showed more jumps compared to Balb/c, Swiss, and CD1 strains. Panic-like jumping in C57B1/6 was enhanced when mice were tested in a small (50 cm×25 cm x 37 cm height) compared to the large arena (150 ×25 cm x 37 cm height) suggesting that the smaller arena enhanced perceived threat. Responses in the small arena were attenuated after prior exposure to the test. Panic-like jumping behavior in the small arena was reduced by pre-treatment with the anti-panic agent clonazepam (0.1 mg kg i.p) and enhanced by treatment with FG-7142 (10 or 20 mg kg i.p.), an panic-inducing drug. Our findings demonstrate that the BMT in the small arena is a reliable model for evaluating non-respiratory panic-like behaviors and also highlights strain-dependent differences in the expression of these responses, with C57BL/6 mice showing the highest reactivity.

This exploratory pilot double-blind, placebo-controlled trial evaluated the effectiveness and safety of combining transcranial direct current stimulation (tDCS) with antidepressants for late-life depression (LLD), and examined whether baseline hippocampal subfield volumes moderated treatment response.

While some animal studies have shown that erythropoietin (EPO) can reduce neuronal death and improve cognitive outcomes after traumatic brain injury (TBI), inconsistencies exist in research findings, possibly due to differences in dosage, timing, and injury models. Specifically, the role of EPO in modulating the AMP-activated protein kinase (AMPK) pathway remain unclear. Thus, this study aims to address these gaps by investigating the effects of EPO on neurobehavioral outcomes, brain edema, blood-brain barrier (BBB) permeability, and the AMPK pathway in a severe TBI rat model.

This study aimed to explore the neurobiology of implicit and explicit suicidal ideation (SI) in depression. Seventy-four patients with major depressive disorder (MDD) along with 74 age- and gender- matched healthy controls were enrolled. The Death/Suicide implicit association test (D/S-IAT), the explicit Beck Scale for Suicidal Ideation (BSSI), and Resting-state functional magnetic resonance imaging (rs-fMRI) scanning were administered. The amplitude of low-frequency fluctuations (ALFF) was calculated and compared between groups to identify brain regions showing spontaneous neural activity related to implicit and explicit SI, and then seed-based functional connectivity (FC) was performed among these regions to reconstruct brain networks related to SI. Behavioral analysis demonstrated higher implicit SI (D values from D/S-IAT) in MDD patients, when compared to HCs，which was also significantly correlated with explicit SI (BSSI scores). Whole brain regression analysis indicated abnormal ALFF in the right postcentral gyrus associated with implicit SI, while ALFF alterations in the left insula, postcentral gyrus, and right middle temporal gyrus (MTG) was associated with explicit SI in MDD. Furthermore, FC analysis revealed increased connectivity between the right postcentral gyrus with the right SFG, MFG, MTG, SPG, insula, and amygdala for implicit SI. Conversely, higher FC between the left insula ROI and left SFG, as well as between the right MTG and left MFG and IPL for explicit SI. These findings suggesting partly overlapped but largely distinct neural basis of the implicit and explicit SI in the brain.

Depression is a clinically heterogeneous disorder with symptom-specific neural correlates. However, systematic mapping of brain networks underlying individual symptoms remains limited, hindering deeper neurobiological understanding.

Eye-blinking has been used to catalog dopaminergic receptor subtype activation in several mammalian species. In this study, the dissimilar effects of directly-acting D and D agonists and an indirectly-acting non-selective agonist (SKF-82958, quinelorane, cocaine, respectively) on eye-blinking were confirmed in marmosets. Subsequently, functional magnetic resonance imaging (fMRI) was used to examine their effects on functional connectivity (FC) between the dopamine-rich putamen and other brain regions. Results indicate that SKF-82958 produced dose-dependent increases in blinking, with the highest dose (0.3 mg/kg) yielding > 9-fold increases over baseline values. In contrast, the highest dose of quinelorane (0.001 mg/kg) reduced blink rates to ∼30 % of baseline. Following the highest dose of cocaine (5.6 mg/kg), only limited (∼20 %) and short-lived (∼20-min) decreases in eye-blinking were observed. In fMRI studies, cocaine induced transient FC increases between putamen and striatal regions, whereas the D and D agonists induced distinct temporal dynamics and region-specific changes in putamen FC. SKF-82958 strengthened putamen FC with motor and sensory regions and reduced FC with visual and cerebellar regions. Conversely, quinelorane reduced putamen connectivity with motor and sensory areas and strengthened FC with regions associated with visual and emotional regulation. These effects in marmosets align with previous outcomes and show that dopamine receptor-subtype activation produce distinct patterns of FC between the putamen and brain regions that play key integrative roles in eye-blinking and other behavior. These findings support eye-blinking as a non-invasive cross-species indicator of dopaminergic subtype activation that can be used to enhance our understanding of dopamine-related dysfunction in neuropsychiatric disorders.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with limited effective treatments. Saikosaponin A (SSa), a bioactive triterpenoid from Bupleurum chinense, exhibits neuroprotective and anti-inflammatory properties, yet its therapeutic potential for PTSD remains unexplored. This study investigated whether SSa ameliorates PTSD-like behaviors in rats and examined the underlying mechanisms. A PTSD rat model was established using single prolonged stress (SPS) combined with footshock(FS). Rats were randomly assigned to control, model, SSa treatment, and fluoxetine-positive control groups. Behavioral assessments included open-field, elevated plus maze, freezing behavior test, and forced swim tests. Hippocampal serotonin (5-HT) levels were measured by high-performance liquid chromatography-mass spectrometry, pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], interleukin-1β [IL-1β]) by enzyme-linked immunosorbent assay (ELISA), and nuclear factor kappa B (NF-κB) p65 protein by was Western blot SSA treatment significantly ameliorated PTSD-like behaviors on days 14 and 21 post-intervention. Mechanistically, SSa restored depleted hippocampal 5-HT levels, reduced pro-inflammatory cytokines expression (TNF-α, IL-6, IL-1β), and suppressed NF-κB p65 activation. These findings demonstrate that SSa exerts therapeutic effect against PTSD-like behavior through dual mechanisms: restoration of hippocampal serotonergic neurotransmission and suppression of NF- κB- mediated neuroinflammation, positioning SSa as a promising candidate for PTSD treatment.

We have previously reported that patients with a history of binge eating disorder or bulimia nervosa are more likely to have rare, damaging mutations in glucagon-like peptide 1 and glucagon-like peptide 1 receptor. Little is known about the role of the closely related glucagon-like peptide 2 (GLP-2) pathway in regulation of feeding behaviors.