Adult olfactory neurogenesis depends largely on the persistence of resident quiescent neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ) and their capacity to reversibly switch to an activated state to generate new neurons. These cells exhibit reduced cell-cycle and biosynthetic activity while maintaining key signaling and stress-response programs. Rather than representing a uniform condition, quiescence encompasses a continuum of substates, ranging from deep to shallow, each characterized by distinct activation thresholds. The dynamics and reversibility of state transitions are regulated by interactions between NSCs and neighboring cells, the extracellular matrix, and systemic factors, among others. With aging, NSCs progressively shift toward deeper quiescent states that are less permissive to activation, thereby reducing overall neurogenic output. Consequently, quiescence should no longer be regarded as a passive pause in stem cell activity, but an organizing principle that underlies the long-term maintenance and adaptability of adult NSCs. A deeper understanding of how quiescence is established, diversified, and dynamically regulated will be essential for elucidating the principles governing adult olfactory neurogenesis and for harnessing its regenerative potential in aging and disease.
Centrifugal mechanisms play a crucial role in supporting sensorimotor integration by modulating sensory processing. Voluntary movements regulate neural activity via centrifugal effects, whereby motor commands from motor areas influence sensory areas. Previous studies have shown that the long-latency somatosensory evoked potentials (SEPs), P100 and N140, increased during stimulus-triggered movement tasks, whereby long-latency auditory evoked potentials (AEPs), N100, were suppressed by self-generated sounds. However, findings were inconsistent regarding stimulus and movement timing. Therefore, the present study was conducted to investigate whether the centrifugal effects differ between somatosensory and auditory modalities. SEPs and AEPs were recorded during movement (button-pressing), attention (stimulus counting), and passive conditions. Difference waveforms were calculated for each modality by subtracting the event-related potentials (ERPs) elicited during attention condition from the ERPs elicited during movement condition. P100, N140, and N1 amplitudes significantly increased during movement compared with attention and/or passive conditions (p < 0.05). Positive components of the difference waveforms were significantly larger in the somatosensory modality than in the auditory modality (p < 0.05). These findings suggest that movement-related modulation may be more pronounced in the SEPs than for AEPs, indicating possible modality-specific differences by centrifugal modulation. However, given the limited electrode coverage, future studies employing high-density EEG will be necessary to clarify whether centrifugal modulation differs across sensory modality.
Despite optimal management, freezing of gait (FOG) remains a disabling complication of Parkinson's disease (PD), contributing substantially to falls, loss of independence and reduced quality of life. This highlights the pressing need for a shift towards preventive approaches, aiming to postpone or even prevent its development. In this narrative review, we examine potential avenues for the secondary prevention of FOG. We discuss how FOG might be prevented specifically, by targeting modifiable risk factors that seem associated with the development of FOG. Examples of potentially effective strategies here include vascular prophylaxis and perhaps avoidance of pulsatile levodopa administration. Secondary prevention efforts also include generic disease-modifying strategies, including pleiotropic interventions such as exercise and nutrition, targeting either persons in the prodromal disease phase or persons with clinically manifest PD, who are still free from FOG. We conclude by discussing future avenues towards FOG prevention.
Following severe spinal cord injury (SCI), transplanted olfactory ensheathing cells (OECs) reduce inhibitory factors and promote axonal outgrowth at the lesion site to help reestablish the circuit connectivity needed for functional recovery. Another promising therapy, electrical epidural stimulation, also helps to reestablish connectivity but targets the caudal spinal cord. This study asked if the combination of OEC transplantation and administration of electrical epidural stimulation during climb training would improve recovery. Inbred Fischer 344 rats received a severe-to-complete SCI and a two-week delayed transplant of OECs, media, or fibroblasts. Rats received electrical epidural stimulation while performing a climbing task 3 times/week. To evaluate connectivity across the injury site, we injected a transsynaptic retrograde tracer GFP-pseudorabies virus into the tibialis anterior of one hindlimb and RFP-pseudorabies virus into the soleus of the other. Scores on the BBB locomotor test improved for all groups over time, but no behavioural differences were detected. Importantly, the GFP-labelled OECs and fibroblasts survived in the injury site for 5.5-6.5 months. OEC treatment greatly increased the density of serotonergic and neurofilament-positive axons in the lesion core versus controls. The percent of neurofilament-positive axons associated with myelin proteins was greater in OEC- than in media-treated rats. We also found evidence of pseudorabies virus-infected propriospinal neurons that express the transcription factor Chx10 above the injury site and some were cholinergic and dually-labelled from antagonistic muscles. These results provide evidence that OEC transplantation combined with electrical epidural stimulation may be a beneficial treatment for severe SCI.
Cortical interneurons are essential for the formation, maturation and functional balance of mammalian brain circuits. Originating in the ventral telencephalon, they migrate into the cortex through organized streams and diversify into multiple inhibitory subtypes. Advances in molecular biology, imaging and single-cell transcriptomics have revealed the remarkable heterogeneity in their development. Understanding their molecular and functional complexity is a gateway to understanding in full their critical roles in neural synchronization, cognitive processes, sleep regulation and their potential links to the emergence of human-specific brain functions. These findings aim to inspire future studies focused on deciphering the origins of human interneuron, the diversity of interneuron functions and their implications for understanding neurodevelopmental disorders.
Age-related declines in neuromuscular performance are well documented; however, the cortical processes underlying these changes remain unclear. This systematic review and meta-analysis compared younger and older adults across key transcranial magnetic stimulation measures of corticospinal and intracortical function, including corticospinal excitability, cortical silent period, intracortical facilitation and intracortical inhibition. Age-related differences in maximal voluntary strength were also quantified as a secondary outcome. A comprehensive literature search identified 52 eligible studies from 1682 records. Methodological quality was evaluated using a modified Downs and Black checklist, and the certainty of evidence was assessed using the GRADE approach. A random-effects model was applied to calculate standardised mean differences (SMDs) with 95% confidence intervals (CIs). Compared to younger adults, older adults produced lower maximal isometric voluntary force (SMD = -0.76) and exhibited reduced resting motor evoked potential amplitudes (SMD = -0.55) and intracortical facilitation (SMD = -0.27). These age-related differences were not observed during active contractions. Cortical silent period duration was longer in older adults (SMD = 0.39). No age-related differences were found in short- or long-interval intracortical inhibition. These findings indicate that ageing is associated with reduced resting corticospinal and intracortical excitability, prolonged cortical silent periods and lower maximal voluntary strength. As neural and strength outcomes were analysed independently, a causal relationship cannot be established, but the parallel pattern points to central neural alterations as plausible targets for future interventions aimed at mitigating age-related neuromuscular decline.
Understanding how prefrontal cortex (PFC) signals evolve over time to support decision-making requires characterizing both the spectral and temporal structure of neural activity. High-gamma (Hγ) power in local field potentials (LFPs) reflects local population firing, yet its role in differentiating cue-driven preference revision, reward expectation, and outcome-related signals during reward-guided decisions remains unclear. We recorded LFPs from the anterior cingulate cortex (ACC), dorsolateral PFC (DLPFC), and orbitofrontal cortex (OFC) in macaques performing a multicue reward-based decision task in which up to four sequential cues indicated the expected reward associated with competing targets. Hγ power was extracted in sliding windows aligned to key task events, and support vector machine classifiers were used to decode cue-driven preference revision, reward expectation, cue value level and position, target choice, and prediction-error contrasts. Hγ responses robustly differentiated preference-reversal from confirmation trials, with subject-specific modulation patterns across PFC subregions. Cue value level and spatial position were reliably decoded across PFC, with stronger differentiation of cue value level in OFC and cue position in DLPFC. Around movement onset, Hγ activity differentiated high versus low expected reward across PFC, with decoding accuracies reaching 85% in ACC. Hγ was also modulated by unexpected reward omission, yielding 78% decoding accuracy from a single OFC channel. These findings demonstrate that Hγ activity across PFC subregions differentiates multiple computationally defined decision variables with distinct temporal profiles and overlapping regional contributions, highlighting Hγ as a robust marker of dynamic reward-guided decision processes.
Freezing of gait (FoG) is frequently triggered during gait initiation, a transition that depends on anticipatory postural adjustments (APAs). However, the neuroanatomical substrates linking brain morphometry to APA control during step initiation in FoG remain unclear. We investigated whether subcortical volumes and cortical thickness in motor-cognitive regions relate to APA features and clinical severity. Forty-four right-handed individuals with midstage PD (26 PD + FoG; 18 PD - FoG) performed step initiation. FreeSurfer-derived regional volumes and cortical thickness were extracted. Associations between morphometry and APA metrics were tested across all participants and within groups. Group differences were tested using the Mann-Whitney U tests, and partial Spearman correlations examined morphometry-clinical and morphometry-APA associations, controlling for UPDRS-III and daily levodopa dose. Compared with PD without FoG, the PD + FoG group showed higher UPDRS-III scores and levodopa doses, lower APA mediolateral amplitudes, and larger amygdala volumes. Across all participants, longer APA duration was associated with smaller putamen, thalamus, and dorsolateral prefrontal cortex volumes, whereas greater APA mediolateral amplitude was associated with lower frontopolar cortical thickness. In PD + FoG, freezing severity and APA features were associated with distinct morphometric patterns across the basal ganglia, thalamus, prefrontal, cingulate, SMA, and insular regions. These findings suggest that gait initiation impairment in PD reflects distributed morphometric alterations rather than a single regional substrate. APA measures may provide mechanistically relevant biomechanical markers for identifying neural systems involved in FoG.
Reliable assessment of infarct severity is essential in experimental stroke research, yet commonly used approaches such as 2,3,5-triphenyltetrazolium chloride (TTC) staining and magnetic resonance imaging require additional tissue processing, specialized equipment, or substantial time and cost. In this study, we developed and validated a rapid visual Infarct Score to determine infarct volume and evaluate neuroprotective efficacy in rat middle cerebral artery occlusion (MCAO) models. A retrospective analysis was performed using data from 315 male Sprague-Dawley rats, including TTC-derived infarct volume, visual Infarct Score, neurological deficit scores, and body weight changes. The Infarct Score demonstrated the strongest correlation with infarct volume among individual indicators in both nontreatment (Rho = 0.71) and treatment cohorts (Rho = 0.68). We further developed a Comprehensive Score by integrating the Infarct Score with the Longa 5-point score at 48 h, which showed the highest overall correlation with infarct volume (Rho = 0.75 in both cohorts) and strong discrimination of infarct severity (AUC = 0.90). Interrater reliability analysis demonstrated excellent agreement among independent raters (intraclass correlation coefficient = 0.89; Kendall's W = 0.83, both p < 0.001). Neuroprotective interventions, including therapeutic hypothermia, nitroglycerin, and remote ischemic conditioning combined with physical exercise, significantly reduced infarct volume, Infarct Score, Comprehensive Score, neurological deficits, and weight loss. These findings indicate that the Infarct Score offers a rapid, practical, and cost-effective method for infarct assessment, whereas the Comprehensive Score further improves the predictive accuracy and may serve as a useful tool for evaluating stroke severity and treatment outcomes in preclinical studies.
Auditory and vestibular symptoms in vestibular migraine, cochlear migraine, and Ménière's disease overlap, yet mechanisms linking migraine biology to inner ear dysfunction remain unclear. Calcitonin gene-related peptide (CGRP) is a key mediator of trigeminovascular activation and a major therapeutic target in migraine, but its contribution to cochlear dysfunction is not well defined. Using a repeated nitroglycerin (NTG) paradigm in male Wistar rats, we investigated whether a systemic migraine-like state affects cochlear function and whether these effects are dependent on CGRP. Rats received saline, NTG, or NTG followed by the CGRP receptor antagonist olcegepant (OLC). NTG increased plasma TNF-α and elevated trigeminal c-Fos; olcegepant partially normalized these markers, whereas behavioral changes in the open-field test were interpreted cautiously because baseline immobility differed across groups before treatment. NTG produced frequency-dependent changes in distortion-product otoacoustic emissions and auditory brain stem response thresholds. Electrocochleography showed limited changes, and scala media proportions did not differ significantly among groups, indicating no evidence of overt endolymphatic hydrops at the studied time point. Inner hair-cell synaptic markers showed no significant group differences for CtBP2, whereas GluR2 puncta differed between NTG and NTG + OLC (p = 0.012). Olcegepant attenuated NTG-associated cochlear functional changes and was associated with differences in postsynaptic GluR2 puncta, alongside region-specific changes in cochlear CGRP immunoreactivity. These findings support a mechanistic link between migraine-like trigeminovascular activation and early cochlear dysfunction and suggest that CGRP receptor blockade may benefit migraine patients with cochlear or vestibular symptoms. Future studies should assess females, estrous cycle tracking, hormones, and sex-specific auditory responses.
Freezing of gait is a debilitating walking disturbance that can severely worsen quality of life for people with Parkinson's disease. However, current Parkinson's disease treatments do not effectively address freezing of gait, leading researchers to explore cueing to mitigate the symptom. Somatosensory stimulation is an emerging cueing strategy that could be discreet and practical to mitigate freezing of gait duration. Twenty-six participants (seven females) attempted walking trials in a freeze-inducing path while wearing a functional electrical stimulation cueing device. Functional electrical stimulation cueing was activated autonomously in real time. Constrained random sampling was used to designate each trial as cueing system on or off, providing a control for within-participant analysis. A total of 576 freezing episodes were recorded with the device on. Of those, 492 were successfully stimulated. To assess cueing performance, freezing of gait time per trial in the on and off device states was calculated for each participant. On average, freezing of gait time per trial decreased from 5.84 to 5.69 s (2.44%). Freezing of gait time per trial increased for half the participants and the other half experienced a decrease. There were no statistically significant group-level effects, though electrical stimulation cueing elicits a wide range of responses from different participants, with the technology mitigating freezing of gait for some individuals. Because functional electrical stimulation has numerous modifiable parameters that influence sensation and nervous system response, personalizing these parameters could enhance the effectiveness of freezing of gait mitigation and provide deeper insights into freezing of gait.
Spinal manipulation (SMA) and spinal mobilization (SMO) are two of the most widely used manual therapy techniques (SMT) for spine-related musculoskeletal pain management. Although their neuromuscular effects have been reported, emerging evidence suggests that SMT may also induce neurophysiological changes within the central nervous system (CNS). This review aimed to synthesize the current literature on the neurophysiological effects of SMT with multiple brain imaging and neurophysiological methods. A scoping review was conducted according to PRISMA guidelines. Eight databases were searched for studies using brain imaging techniques (e.g., transcranial magnetic stimulation [TMS], functional magnetic resonance imaging [fMRI] or electroencephalography [EEG]) to assess the impact of SMT on healthy individuals or those with musculoskeletal spine pain. Twenty-six studies were included: eight TMS, seven fMRI, five somatosensory evoked potential (SEP) and six with other imaging methods (e.g., EEG, positron emission tomography [PET] or magnetic resonance spectroscopy [MRS]). Most studies reported significant postintervention neurophysiological changes, particularly in motor cortex excitability (TMS), functional connectivity (fMRI) and sensorimotor integration (SEP). However, heterogeneity in study design, manipulation protocols, imaging outcomes and timing of assessments limited generalizability of the results. Although many studies reported reductions in pain intensity, none of them linked cortical changes directly to clinical improvements. Overall, SMT can induce changes in cortical activity and connectivity, particularly in pain processing and motor control regions. However, significant methodological variation across studies limits the strength of conclusions. Future research should aim for standardized protocols and investigate the clinical significance of neurophysiological changes in large, diverse populations.
Platinum electrodes are used in many bionic devices; however, they have limited charge injection capacity (CIC) and signal-to-noise ratio (SNR), restricting performance. Iridium oxide has substantially larger CIC and reduced impedance compared to platinum. While these types of electrochemical measurements are typically used to infer improved electrophysiological performance, there are no studies demonstrating this correlation. This article compares the electrochemical and acute electrophysiological recording performance of iridium and electrochemically activated IrOx. Increased iridium activation reduced total impedance at low-intermediate frequencies and steady-state electroactive area but had no impact on linear diffusion electroactive area. The total impedance had a poor correlation with background noise, SNR and spike count. The results contribute to the previous literature indicating linear diffusion electroactive area determines the number of neurons within recording distance of the electrode, impacting SNR and spike count. Measurements of impedance are mainly of benefit as an indirect measure of linear diffusion electroactive area, in which case the measurement and analysis must be performed appropriately. A wide range of IrOx activation states can be produced with increased CIC, without concern of neural recording performance impacts. However, higher oxidation states resulting in electrode dissolution or increase in electrode resistance may limit IrOx chronic performance.
Theories of object-based attention suggest that attending to an object binds its features together. Yet, there is a growing body of work to suggest that the intention to grasp an object can alter the representation of features such that they are separately represented during different stages of motor planning and execution, whereas some object features such as shape and size might form integrated representations when afforded by motor control. However, it remains untested whether these features were integrated as an outcome of the requirements of grasping motor control, or due to attention towards the object in general. Therefore, here we investigated how task-relevancy modulates the integration of grasp-relevant object features. To this end, we recorded electroencephalography while human participants grasped or reached for objects that varied in their orientation and size. Using multivariate analyses, we found a superadditive integration of object orientation and size during action planning for grasping but not reaching. These integrated representations likely facilitated the calculation of stable grasp points as further evidenced by the representations of grasp-specific visual size and grip size emerging at similar times. Our results provide novel insights into the vital role of action intention on cognitive representations in the human brain.
Bilateral organization is a prominent feature of the C. elegans nervous system, yet bilateral neuron pairs differ substantially in their individual left-right connections. Whether, and how, such pairs nonetheless come to occupy similar roles in the network is not fully understood. Here we analyze the adult hermaphrodite and male C. elegans connectomes to examine bilateral redundancy using three complementary graph-theoretic measures: connectivity similarity, which captures overlap in shared in- and out-neighbours; motif-fingerprint difference, which captures the difference in local motif participation (with lower differences indicating greater overlap); and path compensation, which quantifies the extent to which paired neurons make overlapping contributions to global communication. Across measures, bilateral pairs showed elevated redundancy relative to other neuron pairs. Null-model comparisons further supported this finding, demonstrating that these patterns cannot arise from preserving symmetry alone: e.g., for connectivity similarity, randomizing the asymmetric edges while holding the symmetric ones reduced bilateral similarity, suggesting that bilateral asymmetry is itself what enables paired neurons to share neighbours and converge on similar network roles. Redundancy was not uniform across the nervous system: in the hermaphrodite it was more pronounced among interneurons than among sensory neurons across all three measures, while in the male this gradient was only significant for path compensation. Together, these results show that bilateral redundancy is a systematic multiscale principle of the C. elegans connectome, one that cannot be explained by bilateral symmetry alone.
MicroRNAs (miRNAs) play crucial roles in regulating gene expression and have been implicated in the pathophysiology of depression. Among them, miR-124-3p is one of the most abundant brain-enriched miRNAs and has emerged as a potential therapeutic target for mood disorders. This study aimed to evaluate the antidepressant-like effects of an acute administration of miR-124-3p and to identify associated molecular and neuronal changes across key brain regions. Female C57BL/6 mice received intracerebroventricular injections of a miR-124-3p mimic or a control oligonucleotide. Affective-like behavioural responses were assessed using the Porsolt swim test (PST) and the light-dark box test (LDB). Proteomic alterations in the hippocampus, hypothalamus and prefrontal cortex were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and stress-related neuronal activity was evaluated using c-Fos immunofluorescence. Mice treated with the miR-124-3p mimic exhibited reduced immobility in the PST, indicative of an antidepressant-like effect and enhanced active stress coping. Proteomic profiling revealed region-specific changes, including downregulation of immune- and stress-related proteins in the hypothalamus and hippocampus, and upregulation of synaptic and metabolic proteins in the prefrontal cortex. c-Fos analyses showed decreased stress-induced neuronal activation in the hypothalamic paraventricular and periventricular nuclei, alongside increased activity in the hippocampal dentate gyrus. Collectively, these findings suggest that miR-124-3p mimic treatment is associated with antidepressant-like effects by reducing neuroimmune activation and enhancing neuronal plasticity. Our results support a model in which miR-124-3p promotes stress resilience through coordinated modulation of inflammatory and plasticity-related processes across distinct brain circuits.
Autism spectrum disorder manifests through dysbiosis across the microbiota-gut-brain-immune axis, characterized by depletion of short-chain fatty acid (SCFA)-producing taxa like Bifidobacterium, Faecalibacterium, and Roseburia, along with an increase in endotoxin-producing taxa like Desulfovibrio and Bacteroides. SCFA emerge as one of the regulators of neuroimmune homeostasis by governing microglial maturation through GPR43/GPR109A-dependent histone deacetylase inhibition, modulating astrocytic tryptophan-aryl hydrocarbon receptor signaling, and preserving tight junction integrity at blood-brain and blood-CSF barriers. SCFA insufficiency constitutes the upstream metabolic defect linking gut dysbiosis to ASD neuropathology, such as impaired microglial priming and brain-resident CD4+ T cell differentiation, reactive astrocytosis with kynurenine neurotoxicity superseding protective signaling, barrier breakdown enabling LPS-driven TLR4-NF-κB neuroinflammation, and excitatory/inhibitory imbalance from reduced glutamate decarboxylase and astrocyte glutamate dysregulation. This review advances an integrative SCFA-centric framework repositioning ASD as metabolite-dependent neuroimmune dysregulation during brain development. Preclinical and early clinical data demonstrate that SCFA restoration through prebiotic fiber/resistant starch, probiotics, or direct SCFA supplementation normalizes gastrointestinal symptoms, behavioral deficits, microglial morphology, and neurotransmitter ratios. This guides mechanistically targeted microbiota interventions with fecal/plasma SCFA profiling as stratification biomarkers, establishing precision therapeutic regimens for ASD.
The right central amygdala (CeA) is involved in the processing of emotional-affective dimensions of pain. Through the spino-parabrachio-amygdaloid pain pathway, the CeA receives nociceptive information from calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus. Recent evidence indicates that the glutamate delta 1 (GluD1) receptor, an atypical ionotropic glutamate receptor that largely functions as a synaptogenic molecule involved in the formation and maintenance of synapses, regulates this projection in mice. Despite its strong cellular expression, little is known about the subsynaptic localization of GluD1, and its potential interaction with CGRP terminals, in CeA neurons. To address this issue and further characterize the ultrastructure and synaptic connectivity of CGRP terminals across species, we used single and double immuno-electron microscopy techniques in mice and monkeys. For all ultrastructural parameters examined, no species difference was found. In both species, CGRP-positive (CGRP+) terminals formed symmetric or asymmetric synapses with dendrites, symmetric synapses with soma, and less commonly, asymmetric synapses with spines. Almost 90% of CGRP+ terminals forming asymmetric or symmetric synapses expressed vGluT2 immunoreactivity confirming the glutamatergic and peptidergic nature of this projection. Confocal microscopic analyses confirmed the perisomatic association between CGRP+ and GluD1+ puncta in mice and monkeys. At the ultrastructural level, GluD1 was expressed in the core of symmetric axo-dendritic and axo-somatic synapses and perisynaptic to asymmetric synapses formed by CGPR+ terminals. These findings demonstrate that the CGRP+ PB-CeA projection mediates its effects through a heterogeneous population of terminals that display strong synaptic relationships with GluD1 in rodents and primates.
Attachment-related defences are theorized to systematically distort emotional information processing, yet the temporal dynamics of these biases remain poorly understood. The present study elucidated the neurophysiological mechanisms underlying implicit and explicit memory biases in attachment anxiety and avoidance using event-related potentials (ERPs). University students completed both implicit and explicit memory tasks involving attachment-relevant stimuli (threat and positive). Behavioural data revealed a double dissociation; the anxious group exhibited heightened memory sensitivity to threat, whereas the avoidant group showed memory bias toward positive stimuli. ERP findings indicated that avoidant individuals exhibited elevated P200 amplitudes early in processing, followed by a significant inhibition of the late parietal component (LPC). Conversely, attachment anxiety was characterized by elevated FN400 and sustained LPC amplitudes across all emotional stimuli. These results indicate that attachment dimensions differentially modulate distinct stages of neural processing, suggesting that defensive strategies are activated at specific temporal points to either amplify or inhibit specific emotional information.
Chronic stress-induced behavioral changes are partly sex-dependent, but their temporal dynamics remain unclear. Only a few studies have made a direct, comprehensive comparison of sex differences in stress-induced behavioral responses, and most focus on isogenic mouse strains, overlooking the genetic variability inherent to the stress-related disorders. In this study, we applied the chronic unpredictable mild stress (CUMS) model in Swiss mice to elucidate the time course of sex-dependent maladaptive behavioral responses to stress. Adult males and females were exposed to 4, 6, or 8 weeks of CUMS, followed by behavioral assessment and quantification of serum corticosterone. Analysis of the thigmotaxis-related parameters in the open field (OF) revealed distinct temporal patterns between males and females. CUMS-exposed females showed an initial decrease in the OF center exploration (4 weeks), with no changes observed after 6 or 8 weeks. By contrast, males showed decreased OF center exploration only after 4 weeks of stress, with this effect shifting to a decrease after 6 and 8 weeks. Eight weeks of CUMS reduced latency and increased immobility during forced swimming. Moreover, only females showed increased corticosterone levels after 8 weeks of stress, and these levels were moderately correlated with forced-swimming immobility. In conclusion, our results indicate females are more sensitive to stress-induced maladaptive behavioral responses than males, consistent with clinical data showing that women are more prone to stress-induced adverse outcomes than men. Moreover, Swiss mice can be considered highly stress-resilient, requiring longer stress exposure to develop behavioral changes related to depressive-like symptomatology.
