Behavioral Deficits Research Articles

Protective effects of L-carnitine against beta-amyloid-induced memory impairment and anxiety-like behavior in a rat model of Alzheimer's disease

Alzheimer's disease (AD), the most common cause of dementia, leads to neurodegeneration and cognitive decline. We investigated the therapeutic effects of L-carnitine on cognitive performance and anxiety-like behavior in a rat model of AD induced by unilateral intracerebroventricular injection of β-amyloid1-42 (Aβ1-42). L-carnitine (100 mg/kg/day) was administered intraperitoneally for 28 consecutive days. Following this, the open-field test, novel object recognition test, elevated plus-maze test, Barnes maze test, and passive avoidance learning test were used to assess locomotor activity, recognition memory, anxiety-like behavior, spatial memory, and passive avoidance memory, respectively. Plasma and hippocampal oxidative stress markers, including total oxidant status (TOS) and total antioxidant capacity (TAC), were examined. In addition, histological investigations were performed in the dentate gyrus of the hippocampus using Congo red staining and hematoxylin and eosin staining. The injection of Aβ1-42 resulted in cognitive deficits and increased anxiety-like behavior. These changes were associated with an imbalance of oxidants and antioxidants in plasma and the hippocampus. Also, neuronal death and Aβ plaque accumulation were increased in the hippocampal dentate gyrus region. However, injection of L-carnitine improved recognition memory, spatial memory, and passive avoidance memory in AD rats. These findings provide evidence that L-carnitine may alleviate anxiety-like behavior and cognitive deficits induced by Aβ1-42 through modulating oxidative-antioxidant status and preventing Aβ plaque accumulation and neuronal death.

The enduring effects of antimicrobials and lipopolysaccharide on the cellular mechanisms and behaviours associated with neurodegeneration in pubertal male and female CD1 mice

Puberty is a sensitive developmental period during which stressors can cause lasting brain and behavioural deficits. While the acute effects of pubertal lipopolysaccharide (LPS) and antimicrobial (AMNS) treatments are known, their enduring impacts on neurodegeneration-related mechanisms and behaviours remain unclear. This study examined these effects in male and female mice. At five weeks old, mice received 200ul of either broad-spectrum antimicrobials or water through oral gavage twice daily for seven days. At six weeks of age, they received an intraperitoneal injection of either saline or LPS. Four weeks later, adult mice underwent neurodegeneration-related behavioural tests, including the rotarod, forepaw stride length, reversed grid hang, open field, and buried pellet tests. Two days after the final test, brain and ileal samples were collected. Results showed that female mice treated with both AMNS and LPS exhibited deficits in neuromuscular strength, while males treated with LPS alone showed increased anxiety-like behaviours. Males treated with AMNS alone had decreased sigma-1 receptor (S1R) expression in the cornu ammonis 1 (CA1) and dentate gyrus (DG), while females treated with both AMNS and LPS had decreased S1R expression. Additionally, males treated with either LPS or AMNS had lower glial-derived neurotrophic factor receptor alpha-1 (GFRA1) expression in the primary motor cortex (M1) than females. Mice treated with LPS alone had decreased GFRA1 expression in the DG and decreased S1R expression in the secondary motor cortex (M2). These findings suggest that pubertal AMNS and LPS treatments may lead to enduring changes in biomarkers and behaviours related to neurodegeneration.

Chronic stress deficits in reward behaviour co-occur with low nucleus accumbens dopamine activity during reward anticipation specifically

Whilst reward pathologies are major and common in stress-related neuropsychiatric disorders, their neurobiology and treatment are poorly understood. Imaging studies in human reward pathology indicate attenuated BOLD activity in nucleus accumbens (NAc) coincident with reward anticipation but not reinforcement; potentially, this is dopamine (DA) related. In mice, chronic social stress (CSS) leads to reduced reward learning and motivation. Here, DA-sensor fibre photometry is used to investigate whether these behavioural deficits co-occur with altered NAc DA activity during reward anticipation and/or reinforcement. In CSS mice relative to controls: (1) Reduced discriminative learning of the sequence, tone-on + appetitive behaviour = tone-on + sucrose reinforcement, co-occurs with attenuated NAc DA activity throughout tone-on and sucrose reinforcement. (2) Reduced motivation during the sequence, operant behaviour = tone-on + sucrose delivery + sucrose reinforcement, co-occurs with attenuated NAc DA activity at tone-on and typical activity at sucrose reinforcement. (3) Reduced motivation during the sequence, operant behaviour = appetitive behaviour + sociosexual reinforcement, co-occurs with typical NAc DA activity at female reinforcement. Therefore, in CSS mice, low NAc DA activity co-occurs with low reward anticipation and could account for deficits in learning and motivation, with important implications for understanding human reward pathology.

Identifying dysfunctional cell types and circuitsin animal models for psychiatric disorders with calcium imaging.

A central goal of neuroscience is to understand how the brain transforms external stimuli and internal bodily signals into patterns of activity that underlie cognition, emotional states, and behavior. Understanding how these patterns of activity may be disrupted in mental illness is crucial for developing novel therapeutics. It is well appreciated that psychiatric disorders are complex, circuit-based disorders that arise from dysfunctional activity patterns generated in discrete cell types and their connections. Recent advances in large-scale, cell-type specific calcium imaging approaches have shed new light on the cellular, circuit, and network-level dysfunction in animal models for psychiatric disorders. Here, we highlight a series of recent findings over the last ~10 years from in vivo calcium imaging studies that show how aberrant patterns of activity in discrete cell types and circuits may underlie behavioral deficits in animal models for several psychiatric disorders, including depression, anxiety, autism spectrum disorders, and schizophrenia. These advances in calcium imaging in pre-clinical models demonstrate the power of cell-type-specific imaging tools in understanding the underlying dysfunction in cell types, activity patterns, and neural circuits that may contribute to disease and provide new blueprints for developing more targeted therapeutics and treatment strategies.

Prenatal low-dose Bisphenol A exposure impacts cortical development via cAMP-PKA-CREB pathway in offspring.

Bisphenol A (BPA) is a widely used plasticizer known to cause various disorders. Despite a global reduction in the use of BPA-containing products, prenatal exposure to low-dose BPA, even those below established safety limits, has been linked to neurological and behavioral deficits in childhood. The precise mechanisms underlying these effects remain unclear. In the present study, we observed a significant increase in the number of cortical neurons in offspring born to dams exposed to low-dose BPA during pregnancy. We also found that this prenatal exposure to low-dose BPA led to increased proliferation but reduced migration of cortical neurons. Transcriptomic analysis via RNA sequencing revealed an aberrant activation of the cAMP-PKA-CREB pathway in offspring exposed to BPA. The use of H89, a selective PKA inhibitor, effectively rescued the deficits in both proliferation and migration of cortical neurons. Furthermore, offspring from dams exposed to low-dose BPA exhibited manic-like behaviors, including hyperactivity, anti-depressant-like responses, and reduced anxiety. While H89 normalized hyperactivity, it didn't affect the other behavioral changes. These results suggest that the overactivation of PKA plays a causative role in BPA-induced changes in neuronal development. Our data also indicate that manic-like behaviors induced by prenatal low-dose BPA exposure may be influenced by both altered neuronal development and abnormal PKA signaling in adulthood.

Psychological Factors Affecting Assertiveness in Subjects with Parkinson's Disease.

Background/Objectives: Assertiveness, defined as the positive affirmation of oneself, encompasses the ability to refuse requests, express anger, disagree or oppose others, show affection, and uphold personal beliefs without causing conflict. Deficits in assertive behavior are often linked to pathological changes in the basal ganglia and prefrontal dopaminergic systems, commonly observed in Parkinson's disease (PD), and are predictive of poor clinical outcomes. Psychological factors such as mood alterations and cognitive dysfunction may also impact assertiveness. This study investigated the psychological factors influencing assertiveness in individuals with PD. Methods: A cross-sectional study was conducted, involving 160 patients with PD attending a movement disorders outpatient clinic. The participants underwent assessment using a battery of standardized neuropsychological tests to evaluate cognitive function, assertiveness, mood, dysarthria, and quality of life (QoL). Results: All dimensions of assertiveness correlated with depression and anxiety. Individuals experiencing mood disturbances may struggle to express themselves assertively. Similarly, some dimensions of assertiveness correlated also with the QoL, indicating that, overall, well-being affects assertive behavior. Gender emerged as a significant influencer of assertiveness across all dimensions. Specifically, in subjects with PD, the male gender was associated with lower scores in assertiveness compared to women. No significant correlations were found between assertiveness and dysarthria. Conclusions: The findings highlight the importance of adopting a holistic approach to PD management, addressing not only motor symptoms but also psychological challenges which patients may encounter in their daily lives.

Social deficits mirror delayed cerebrovascular dysfunction after traumatic brain injury

Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. TBI modifies neurovascular physiology and behavior but the chronic physiological implications of altered brain perfusion on social interactions are unknown. Adult C57/BL6 male mice received a moderate cortical TBI, and social behaviors were assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi). Magnetic resonance imaging (MRI, 9.4T) using dynamic susceptibility contrast perfusion weighted MRI were acquired. At 60dpi mice underwent histological angioarchitectural mapping. Analysis utilized standardized protocols followed by cross-correlation metrics. Social behavior deficits at 60dpi emerged as reduced interactions with a familiar cage-mate (partner) that mirrored significant reductions in cerebral blood flow (CBF) at 60dpi. CBF perturbations were dynamic temporally and across brain regions including regions known to regulate social behavior such as hippocampus, hypothalamus, and rhinal cortex. Social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interactions. Thus, the late emergence of social interaction deficits mirrored the reduced vascular density and CBF in regions known to be involved in social behaviors. Vascular morphology and function improved prior to the late decrements in social function and our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions. Our study provides a clinically relevant timeline of alterations in social deficits alongside functional vascular recovery that can guide future therapeutics.

Selective deletion of Tsc1 from mouse cerebellar Purkinje neurons drives sex-specific behavioral impairments linked to autism.

There is a striking sex bias in the prevalence and severity of autism spectrum disorder (ASD) with 80% of diagnoses occurring in males. Because the molecular etiology of ASD is likely combinatorial, including interactions across multiple genetic and environmental factors, it is difficult to investigate the physiological mechanisms driving sex-specific differences. Loss of function mutations in TSC1 result in dysregulated mTORC1 signaling and underlie a multi-system disorder known as tuberous sclerosis (TSC). Interestingly, more than 50% of individuals diagnosed with TSC are also diagnosed with ASD, making TSC mutations one of the most prevalent monogenic causes of ASD. Mice harboring targeted deletion of Tsc1 selectively in cerebellar Purkinje neurons, referred to here as Tsc1 mut/mut , have multiple ASD-linked behavioral impairments, including deficits in social interactions, motor coordination, and vocalizations. However, these ASD-linked behavioral deficits have only been investigated using male Tsc1 mut/mut animals. Here, we used cohorts of male and female Tsc1 mut/mut animals to determine if behavioral impairments, previously identified in this model, are similar across sex. Specifically, we measured balance and motor coordination and social interaction behaviors in two age groups across sex. W e determined balance and motor coordination deficits are similar in male and female Tsc1 mut/mut mice, and that deficits in the firing of Tsc1 mut/mut Purkinje neurons located in the cerebellar vermis are also similar across sex. However, impairments in social approach behavior were found to be significantly more severe in Tsc1 mut/mut males compared to females. These results indicate the selective deletion of Tsc1 in Purkinje neurons differentially impairs cerebellar circuits based on sex.

Primary cilia signaling in astrocytes mediates development and regional-specific functional specification.

Astrocyte diversity is greatly influenced by local environmental modulation. Here we report that the majority of astrocytes across the mouse brain possess a singular primary cilium localized to the cell soma. Comparative single-cell transcriptomics reveals that primary cilia mediate canonical SHH signaling to modulate astrocyte subtype-specific core features in synaptic regulation, intracellular transport, energy and metabolism. Independent of canonical SHH signaling, primary cilia are important regulators of astrocyte morphology and intracellular signaling balance. Dendritic spine analysis and transcriptomics reveal that perturbation of astrocytic cilia leads to disruption of neuronal development and global intercellular connectomes in the brain. Mice with primary ciliary-deficient astrocytes show behavioral deficits in sensorimotor function, sociability, learning and memory. Our results uncover a critical role for primary cilia in transmitting local cues that drive the region-specific diversification of astrocytes within the developing brain.

Microglial type I interferon signaling mediates chronic stress-induced synapse loss and social behavior deficits.

Inflammation and synapse loss have been associated with deficits in social behavior and are involved in pathophysiology of many neuropsychiatric disorders. Synapse loss, characterized by reduction in dendritic spines can significantly disrupt synaptic connectivity and neural circuitry underlying social behavior. Chronic stress is known to induce loss of spines and dendrites in the prefrontal cortex (PFC), a brain region implicated in social behavior. However, the underlying mechanisms are not well understood. In the present study, we investigated the role of type I Interferon (IFN-I) signaling in chronic unpredictable stress (CUS)-induced synapse loss and behavior deficits in mice. We found increased expression of type I IFN receptor (IFNAR) in microglia following CUS. Conditional knockout of microglial IFNAR in adult mice rescued CUS-induced social behavior deficits and synapse loss. Bulk RNA sequencing data show that microglial IFNAR deletion attenuated CUS-mediated changes in the expression of genes such as Keratin 20 (Krt20), Claudin-5 (Cldn5) and Nuclear Receptor Subfamily 4 Group A Member 1 (Nr4a1) in the PFC. Cldn5 and Nr4a1 are known for their roles in synaptic plasticity. Krt20 is an intermediate filament protein responsible for the structural integrity of epithelial cells. The reduction in Krt20 following CUS presents a novel insight into the potential contribution of cytokeratin in stress-induced alterations in neuroplasticity. Overall, these results suggest that microglial IFNAR plays a critical role in regulating synaptic plasticity and social behavior deficits associated with chronic stress conditions.

Early postnatal whisker deprivation cross-modally modulates prefrontal cortex myelination and leads to social novelty deficit

Sensory experience affects not only the corresponding primary sensory cortex, but also synaptic and neural circuit functions in other brain regions in a cross-modal manner. However, it remains unclear whether oligodendrocyte (OL) generation and myelination can also undergo cross-modal modulation. Here, we report that while early life short-term whisker deprivation from birth significantly reduces in the number of mature of OLs and the degree of myelination in the primary somatosensory cortex(S1) at postnatal day 14 (P14), it also simultaneously affects the primary visual cortex (V1), but not the medial prefrontal cortex (mPFC) with a similar reduction. Interestingly, when mice were subjected to long-term early whisker deprivation from birth (P0) to P35, they exhibited dramatically impaired myelination and a deduced number of differentiated OLs in regions including the S1, V1, and mPFC, as detected at P60. Meanwhile, the process complexity of OL precursor cells (OPCs) was also rduced, as detected in the mPFC. However, when whisker deprivation occurred during the mid-late postnatal period (P35 to P50), myelination was unaffected in both V1 and mPFC brain regions at P60. In addition to impaired OL and myelin development in the mPFC, long-term early whisker-deprived mice also showed deficits in social novelty, accompanied by abnormal activation of c-Fos in the mPFC. Thus, our results reveal a novel form of cross-modal modulation of myelination by sensory experience that can lead to abnormalities in social behavioral, suggesting a possible similar mechanism underlying brain pathological conditions that suffer from both sensory and social behavioral deficits, such as autism spectrum disorders.

The Projection-Specific Noradrenergic Modulation of Perseverative Spatial Behavior in Adult Male Rats.

Adaptive behavior relies on efficient cognitive control. The anterior cingulate cortex (ACC) is a key node within the executive prefrontal network. The reciprocal connectivity between the locus ceruleus (LC) and ACC is thought to support behavioral reorganization triggered by the detection of an unexpected change. We transduced LC neurons with either excitatory or inhibitory chemogenetic receptors in adult male rats and trained rats on a spatial task. Subsequently, we altered LC activity and confronted rats with an unexpected change of reward locations. In a new spatial context, rats with decreased noradrenaline (NA) in the ACC entered unbaited maze arms more persistently which was indicative of perseveration. In contrast, the suppression of the global NA transmission reduced perseveration. Neither chemogenetic manipulation nor inactivation of the ACC by muscimol affected the rate of learning, possibly due to partial virus transduction of the LC neurons and/or the compensatory engagement of other prefrontal regions. Importantly, we observed behavioral deficits in rats with LC damage caused by virus injection. The latter finding highlights the importance of careful histological assessment of virus-transduced brain tissue as inadvertent damage of the targeted cell population due to virus neurotoxicity or other factors might cause unwanted side effects. Although the specific role of ACC in the flexibility of spatial behavior has not been convincingly demonstrated, our results support the beneficial role of noradrenergic transmission for an optimal function of the ACC. Overall, our findings suggest the LC exerts the projection-specific modulation of neural circuits mediating the flexibility of spatial behavior.

Abstract task sequence initiation deficit dissociates anxiety disorders from obsessive-compulsive disorder and healthy controls.

In everyday life, humans perform sequences of tasks. These tasks may be disrupted in people with obsessive-compulsive disorder (OCD). Symptoms, such as compulsions, can be considered sequential and often cause repetitions of tasks that disrupt daily living (e.g., checking the stove while cooking). Motor sequences have been used to study behavioral deficits in OCD. However, not all sequences are motor sequences. Some are more "abstract" in that they are composed of a series of tasks (e.g., chopping and stirring) rather than being dependent on individual actions or stimuli. These abstract task sequences require cognitive control mechanisms for their execution. Although theory has proposed deficits in these sequences in OCD as well, they have not been directly investigated. We tested the hypotheses that OCD participants exhibit deficits in the control mechanisms specific to abstract task sequences and more general flexible behavior (measured with task switching within the sequences), relative to health controls (HCs) and clinical controls (participants with anxiety disorders [ANX]). A total of 112 participants completed abstract task sequences consisting of simple categorization tasks. Surprisingly, participants with OCD did not perform worse than HCs or ANX. However, ANX participants showed impairments specific to sequential control that did not extend to more general flexible control. Thus, we showed a novel behavioral dissociation between OCD and ANX specific to abstract task sequential control. These results also implicate deficits in specific frontal sequential control neural circuitry in ANX and not in OCD, where implicit sequential deficits may more closely align with striatal circuits.

Effects of adolescent intermittent ethanol exposure on cortical perineuronal net and parvalbumin expression in adulthood mediate behavioral inflexibility.

Alcohol is commonly consumed by adolescents in a binge-like pattern, which can lead to long-lasting cognitive deficits, including reduced behavioral flexibility. We and others have determined that adolescent intermittent ethanol (AIE) exposure leads toincreased number of perineuronal net (PNN) numbers in brain regions that are important for behavioral flexibility. However, whether altered neurochemistry stemming from AIE exposure plays a significant role in reduced behavioral flexibility is unknown. We measured the number and size of parvalbumin expressing (PV+) interneurons and associated PNNs within the orbitofrontal cortex (OFC), prelimbic cortex (PrL), infralimbic cortex (IL), and anterior insular cortex (AIC) of female and male rats following AIE or control exposure and subsequent training on an attentional set-shift task (ASST). We then ran analyses to determine whether AIE-induced changes in PV and PNN measures statistically mediated the AIE-induced behavioral deficit in reversal learning. We demonstrate that AIE exposure impaired behavioral flexibility on reversal two of the ASST (i.e., recalling the initial learned associations), and led to smaller PV+ cells and increased PNN numbers in the AIC. Interestingly, PNN size and number were not altered in the PrL or IL following AIE exposure, in contrast to prior reports. Mediation analyses suggest that AIE alters behavioral flexibility, at least in part through changes in PV and PNN fluorescent measures in the AIC. This study reveals a significant link between AIE exposure, neural alterations, and diminished behavioral flexibility in rats, and highlights a potential novel mechanism comprising changes in PV and PNN measures within the AIC. Future studies should explore the impact of PNN degradation within the AIC on behavioral flexibility.

Pioglitazone ameliorates sepsis-associated encephalopathy through SIRT1 signaling pathway

Sepsis is a severe immune response to an infection. It is associated with multiple organ dysfunction syndrome (MODs) along with systemic and neuronal inflammatory response. This study focused on the acute neurologic dysfunction associated with sepsis by exploring the role of PPARγ/SIRT1 pathway against sepsis. We studied the role of this axis in ameliorating sepsis-associated encephalopathy (SAE) and its linked neurobehavioral disorders by using pioglitazone (PIO). This PPARγ agonist showed neuroprotective actions in neuroinflammatory disorders. Sepsis was induced in mice by LPS (10 mg/kg). Survival rate and MODs were assessed. Furthermore, behavioral deficits, cerebral oxidative, inflammatory, and apoptotic markers, and the cerebral expression level of SIRT1 were determined. In this study, we observed that PIO attenuated sepsis-induced cerebral injury. PIO significantly enhanced survival rate, attenuated MODs, and systemic inflammatory response in septic mice. PIO also promoted cerebral SIRT1 expression and reduced cerebral activation of microglia, oxidative stress, HMGB, iNOS, NLRP3 and caspase-3 along with an obvious improvement in behavioral deficits and cerebral pathological damage induced by LPS. Most of the neuroprotective effects of PIO were abolished by EX-527, a SIRT1 inhibitor. These results highlight that the neuroprotective effect of PIO in SAE is mainly SIRT1-dependent.

The Effects of Rearing Environment on Organization of the Olfactory System and Brain of Juvenile Sockeye Salmon, Oncorhynchus nerka.

Pacific salmon (Oncorhynchus spp.) hatch and feed in freshwater habitats, migrate to sea to mature, and return to spawn at natal sites. The final, riverine stages of the return migrations are mediated by chemical properties of the natal stream that they learned as juveniles. Like some other fish, salmon growth is asymptotic; they grow continuously throughout life toward a maximum size. The continued growth of the nervous system may be plastic in response to environmental variables. Due to the ecological, cultural, and economic importance of Pacific salmon, individuals are often reared in hatcheries and released into the wild as juveniles to supplement natural populations. However, hatchery-reared individuals display lower survivorship and may also stray (i.e., spawn in a non-natal stream) at higher rates than their wild counterparts. Hatchery environments may lack stimuli needed to promote normal development of the nervous system, thus leading to behavioral deficits and a higher incidence of straying. This study compared the peripheral olfactory system and brain organization of hatchery-reared and wild-origin sockeye salmon fry (Oncorhynchus nerka). Surface area of the olfactory rosette, diameter of the olfactory nerve, total brain size, and size of major brain regions were measured from histological sections and compared between wild and hatchery-origin individuals. Hatchery-origin fish had significantly larger optic tecta, and marginally insignificant, yet noteworthy trends, existed in the valvula cerebelli (hatchery>wild) and olfactory bulbs (hatchery<wild). We also found a putative difference in olfactory nerve diameter (dmin) (hatchery>wild), but the validity of this finding needs further analyses with higher resolution methods. Overall, these results provide insight into the potential effects of hatchery rearing on nervous system development in salmonids, and may explain behavioral deficits displayed by hatchery-origin individuals post-release.

Cognitive and Behavioral Profile of Patients with Amyotrophic Lateral Sclerosis Spectrum in the Indian Context.

Amyotrophic lateral sclerosis (ALS) is characterized by motor, cognitive, and behavioral impairment. There is a paucity of evidence about the cognitive/behavioral features of ALS patients from India. We aimed to investigate the cognitive/behavioral profile of ALS spectrum disorders in the Indian context. Sixty patients with ALS spectrum and 40 age-, gender-, and education-matched healthy controls were recruited. The scales used were Addenbrooke's Cognitive Examination (ACE-III), Clinical Dementia Rating (CDR) scale, and Frontal Systems Behavior (FrSBe) Scale. The mean age of the overall cohort was 55 years, and male-to-female ratio was 2.5:1. The mean duration of illness of the cohort was 16 months. Patients were classified as ALS with normal cognition (ALS-cn, n = 21), mild cognitive or behavioral deficits (ALS-ci/-bi, n = 28), and frontotemporal dementia (ALS-FTD, n = 11). ALS-cn had poorer scores compared to healthy controls in global cognition, memory, and language (p &lt; 0.05). ALS-ci/-bi performed poorer than healthy controls on all cognitive domains (p &lt; 0.05). ALS-FTD had poorer scores than healthy controls and ALS-cn on all cognitive domains (p &lt; 0.001). Behavioral assessment showed an increase in apathy among all subtypes. ALS-FTD showed significant worsening in disinhibition and executive function compared to ALS-cn and ALS-ci/-bi. Our findings suggest that there are key cognitive and behavior characteristics in Indian patients with ALS spectrum. This further strengthens the evidence of a cognitive continuum in ALS and FTD in a diverse context and highlights the importance of meticulous evaluation and correct diagnosis that would assist in better management.

Emotional and Behavioural Problems in Spanish University Students: Association with Lifestyle Habits and Mental Well-Being.

Emotional health represents a significant burden on the mental health of university students. Adapting to a new learning environment and facing increased academic pressure make this period particularly vulnerable for their emotional health and well-being. The objective of the study was to analyse the prevalence of emotional and behavioural problems in university students and their association with lifestyle habits, and mental and physical health indicators. A cross-sectional study was conducted on a sample of 1268 students (23.65 ± 7.84 years) from a university in northern Spain during November 2020 and March 2021. An online questionnaire was administered, comprising the self-report Strengths and Difficulties questionnaire, the Trait Meta-Mood Scale, the Rosenberg Self-Esteem Scale, the Satisfaction with Life Scale, the Perceived Stress Scale, the SENTIA-Brief Scale, the KIDMED questionnaire, the International Physical Activity Questionnaire-Short Form, the Alcohol Use Disorders Identification Test, and the Compulsive Internet Use Scale. 27.60% of students exhibited some form of emotional and behavioural problem. Students who did not present emotional and behavioural problems showed lower perceived stress, reduced suicidal behaviour and emotional intelligence deficits, as well as lower alcohol consumption and compulsive internet use (p < 0.001). Additionally, they reported higher engagement in physical activity and greater adherence to the Mediterranean diet (p < 0.001). The study shows that emotional and behavioural problems are recurring among university students, and given that modifiable psychosocial and lifestyle factors are associated with these issues, it underscores the need to develop multidisciplinary intervention strategies.

ATP-sensitive potassium channel opener, Nicorandil, inhibits NF-κB/AIM2/GSDMD pathway activation to protect against neuroinflammation in ischemic stroke

The absent in melanoma 2 (AIM2) inflammasome contributes to ischemic brain injury by inducing cell pyroptosis and inflammatory responses. Our research group has previously demonstrated that ATP-sensitive potassium channels (KATP channels) openers can modulate neuronal synaptic plasticity post-ischemic stroke for neuroprotection. However, the specific mechanisms of KATP channels in the inflammatory response following ischemic stroke remain unclear. Here, we assessed cellular damage by observing changes in BV-2 morphology and viability. 2,3,5-Triphenyl tetrazolium chloride (TTC) staining, mNSS scoring, Nissl staining, and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to evaluate behavioral deficits, brain injury severity, and neuronal damage in mice subjected to middle cerebral artery occlusion (MCAO). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were used to measure cell pyroptosis and nuclear factor-kappaB (NF-κB) activation in vivo and in vitro. We observed that AIM2 protein expression was upregulated and localized within the cytoplasm of BV-2 cells. Notably, low-dose Nicorandil treatment reduced inflammatory cytokine secretion and pyroptosis-related protein expression, including AIM2, cleaved cysteinyl aspartate-specific protease-1 (cleaved caspase-1), and Gasdermin D N-terminal (GSDMD-NT). Further investigations revealed that the KATP channel inhibitor 5-HD upregulated p-NF-κB p65, NF-κB p65, and p-IκBα expression, reversing Nicorandil's neuroprotective effect in vivo. In summary, our results suggest that Nicorandil may serve as a potential therapeutic option for ischemic stroke. Targeting AIM2 and NF-κB represents effective strategies for inhibiting neuroinflammation.

Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology.

Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, while semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE as well as 60 age and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, both in the MTL and in neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, on the other hand, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, while hippocampal functional topographies were unaffected. Leveraging MRI proxies of MTL pathology, we furthermore observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic, but again not semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, while episodic processes are supported by a network involving both the hippocampus and neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE.