Steroid sulfatase (STS) cleaves sulphate groups from steroid hormones. In humans, STS deficiency is associated with X-linked ichthyosis, an increased predisposition to neurodevelopmental and mood conditions (including Attention Deficit Hyperactivity Disorder, autism, depression and anxiety), and cardiac arrhythmia risk. Until recently, no single-gene 'knockout' mammalian model existed; previous work in such a model is limited to skin phenotypes. We generated a novel C57BL/6J mouse model with a deletion in exon 2 of Sts. We examined gene expression and enzyme activity in liver and brain samples of homozygous mice, and assessed the breeding performance and health of male and female deletion-carriers. Subsequently, we compared performance across a range of behavioural paradigms in wildtype and homozygous male and female mice: elevated plus maze, open field, rotarod, spontaneous alternation, and acoustic startle/prepulse inhibition. We also investigated serum steroid hormone levels by liquid chromatography-mass spectrometry and measured heart weights and two morphological indices (bodyweight/tibia length) post mortem. Homozygous mice almost completely lacked STS expression/activity. Genetically-altered mice exhibited grossly-normal breeding performance, health, and endocrinology. Homozygous mice were more active and had higher normalised heart weights than wildtype mice. We also found significant genotype × sex interactions on bodyweight and on two behavioural measures (potentially reflecting lower anxiety in homozygous males and heightened anxiety in homozygous females). The 'Sts-deletion' mouse represents an experimentally-tractable model in which to identify and characterise phenotypes associated with STS deficiency. The mechanistic basis of the associations described here requires further investigation, and whether these translate to humans remains to be tested.
Schizophrenia (SCZ) is a highly heritable psychiatric disorder, yet its genetic links with chronic pulmonary diseases remain poorly defined. Such links may reflect shared biological pathways and could create opportunities for cross-disorder risk prediction and therapeutic repurposing. Here we applied a multiancestry, multitrait GWAS framework to SCZ and chronic pulmonary disease datasets. The analysis included 322,321 participants of European and East Asian ancestry from the Psychiatric Genomics Consortium, FinnGen, and 23andMe. We identified 16 previously unreported genetic variants associated with schizophrenia across ancestries. Transcriptome-wide association analysis and machine learning prioritization highlighted candidate genes, including WBP1L and CNNM2, that may contribute to schizophrenia biology. Gene-expression-based drug repurposing further nominated potential therapeutic opportunities shared across psychiatric and pulmonary traits. These findings indicate that schizophrenia and chronic pulmonary diseases share part of their inherited architecture, supporting integrated genetic models for comorbidity, risk stratification, and therapeutic discovery.
Major depression, bipolar disorder, and schizophrenia are common mental illnesses, and their potential association with arrhythmias has long been a focus of clinical and research interest. To explore the possible causal relationship between these mental disorders and arrhythmias, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis using publicly available GWAS summary statistics. The primary analysis employed the inverse-variance weighted (IVW) method, with sensitivity analyses including MR-Egger regression and the weighted median estimator to assess robustness and address potential pleiotropy. Results indicated that genetic predisposition to major depression was associated with increased risks of atrial fibrillation/flutter (IVW: OR = 1.214, 95% CI: 1.092-1.349, p < 0.001), paroxysmal tachycardia (IVW: OR = 1.493, 95% CI: 1.261-1.769, p < 0.001), and atrioventricular block (IVW: OR = 1.257, 95% CI: 1.147-1.377, p < 0.001). Reverse MR also suggested a modest effect of atrioventricular block on depression risk (IVW: OR = 1.045, 95% CI: 1.011-1.079, p = 0.008). In conclusion, from the perspective of genetic liability and using the MR framework, our analysis supports a causal role of major depression in increasing the risk of several arrhythmias and suggests potential bidirectional causal effects between depression and atrioventricular block.
Dietary stereotypes driven by health anxiety weaken the assumption that higher taste preference of a food necessarily implies higher intake, potentially mismatching ancestrally imprinted nutrient-handling tendencies with modern diets. We tested whether inherited nutrient predispositions exist and mediate the associations between taste preferences and disease susceptibility. A total of 137 taste-preferences and more than 850 nutrient biomarkers were included for analysis, with seven common gastroduodenal diseases specified as outcomes. Mediation by nutrient predispositions was quantified using a causal-chain model; genetic collinearity along preference-disease links was assessed using Bayesian tests. Maximum-likelihood estimation was applied as a validation analysis for the primary results. External East Asian cohorts were further used to compare and replicate effects observed in the European cohorts. We identified 36 significant causal chains across four gastroduodenal diseases. Mediation involved 14 nutrient or metabolic predispositions. The maximum-likelihood method provided additional confirmation of the initial effect estimates. Cross-ancestry analyses using external cohorts showed directionally consistent effects in East Asian and European cohorts. In comparisons for five foods, only white bread showed concordant associations for both intake and preference with gastric adenocarcinoma risk. Individuals with different taste preferences show marked differences in susceptibility to the same disease, because taste preferences which are inherited across generations shape inter-individual nutrient predispositions. This implicates behavior-gene coevolution as a key driver of divergent disease susceptibility among individuals consuming the same diet. When using intake as the exposure in diet-disease studies, stratifying by taste preference is advisable to mitigate genetic confounding.
Reeler mice have a mutation in the reelin gene. As a result, Reeler mice lack cortical layers, yet their brains are still largely functional. However, Reeler mice display strong motor phenotypes, including ataxic gait and tics, and we posit that their whisking behaviour might also be disrupted. We used high-speed video to film and track whisker movements in 9 adult Reeler mice and 9 age-matched controls in three whisker movement assessment tasks, including our established novel object exploration and open field tasks, as well as a new open field habituation task. Overall, whisker movements in Reeler mice were highly conserved during the novel object exploration and open field tasks, and they demonstrated all behaviourally relevant whisking features during exploratory contact with an object, including contact-induced asymmetry, spread reduction, and decreasing whisker speeds following object contact. In the habituation task, whisker angular position and whisker spread decreased between the first consecutive sessions in all mice, suggesting that the animals were less focused on sampling the area as they got more familiar with the environment. However, only Reeler mice were affected by more extensive habituation. We suggest that whisker-dependent sensory function is surprisingly intact in Reeler mice. However, our observed habituation-related changes in Reeler mice whisker movements suggest some behavioural differences in these mice, which is a likely result of their disorganised cortex due to reelin deficiency.
Autism spectrum disorder (ASD) is characterized by social impairments and stereotyped behavior, with some individuals exhibiting heightened aggression in response to stress. This stress induced aggression (SIA) can severely impact quality of life, yet its underlying neural mechanisms remain poorly understood. Here, we investigated the behavioral phenotypes and neural activity that result as a consequence of stress in Cntnap2-/-:TRAP2+/-:Ai14+/- mice. Deletion of the CNTNAP2 gene leads to a highly penetrant syndromic form of ASD, and the targeted recombination in active populations (TRAP) system allows for permanent access to neuronal populations activated during a specific experience, such as stress and aggression. We implemented a behavioral paradigm consisting of a baseline resident intruder assay, with either a single day or four consecutive days of restraint stress, followed by a posttest resident intruder assay in Cntnap2-/-:TRAP2+/-:Ai14+/- and control mice. While a single day of restraint stress failed to induce changes in aggressive behavior in either genotype, 4 days of restraint stress significantly escalated aggression and reduced latency to attack selectively in Cntnap2-/- mice. Using TRAP-based labeling, we observed increased neuronal activity in the lateral septum, lateral habenula, lateral hypothalamus, nucleus accumbens, and prelimbic cortex of Cntnap2-/- mice. Interestingly, time aggressive and aggressive events were positively correlated with activity in the lateral septum, lateral habenula, and infralimbic cortex. These findings suggest that repeated stress engages specific fronto-striatal and limbic regions in Cntnap2-/- mice and provide insight into the neural substrates of maladaptive SIA, offering a foundation for targeted therapeutic strategies.
Studies have shown that substance use liability is associated with novelty seeking, anxiety-like behavior, and pain sensitivity. We examined whether common genetic variation in outbred Sprague-Dawley rats explained variation in behavioral measures from three assays with established links to substance use: locomotor response to a novel environment, elevated plus maze, and tail flick. We estimated single-nucleotide polymorphism heritability and performed genome-wide association analyses using permutation-derived significance thresholds (N=534-654 rats across traits). Heritability estimates ranged from 0.14-0.38 across eleven traits. Three independent loci were identified: chromosome 1 for elevated plus maze open-arm behavior (α=0.05), chromosome 14 for elevated plus maze immobility (α=0.10), and chromosome 17 for tail flick latency (α=0.05). Candidate genes included Slc18a2, Gfra1, and Pdzd8 (chromosome 1); Rel and Bcl11a (chromosome 14); and Eci2 and Eci3 (chromosome 17). We compared these loci with our genome wide association study of a F2 intercross of selectively bred high- and low-responder rats, originally derived from Sprague-Dawleys, that model individual differences in externalizing and internalizing behavior. The current loci are distinct from the ones identified in the bred lines. This difference likely reflects selection history in the high- and low-responder F2s, which focused on facets of exploratory locomotion, while loci for anxiety and pain sensitivity traits were identified in the outbreds. This highlights the benefit of using both outbred and selectively bred rats to probe causal variants contributing to individual differences in substance use liability. The current outbred findings implicate monoaminergic signaling, transcriptional control, and lipid metabolism as testable mechanisms for addiction-relevant behaviors.
Along with increasing an animal's lifespan, calorie restriction (CR) is shown to improve an animal's cognition. To elucidate the molecular differences that accompany CR that may benefit cognition, sibling Aplysia californica were reared on either an ad-lib (AL) or CR diet. Siblings from each diet were trained in two behaviors, learning food is inedible (LFI) and habituation of the tail withdrawal reflex (TWR), at two time points along their lifespans: younger animals at training time 1 (TT1) and aged siblings at training time 2 (TT2). In analysis by diet, TT2 CR animals' learning performance was on par with their TT1 CR siblings in both paradigms, illustrating a maintenance of cognition in age. Meanwhile, TT2 AL animals performed worse than TT1 AL siblings in habituation but better in LFI, illustrating the lack of cognitive maintenance in age. RNA sequencing was performed on part of the buccal ganglia that houses many of the neurons involved in LFI. Gene expression results implied morphological changes occurring within the motor and interneurons of the buccal ganglia after learning in LFI. These neurons showed enrichment of protein kinase C binding (GO:0005080), cadherin binding (GO:0045296), and microtubule severing ATPase activity (GO:0008568) as well as neuroactive ligand-receptor interaction (ko04080) and valine, leucine and isoleucine biosynthesis (ko00290) all of which have been implicated to assist in memory consolidation and reconsolidation.
Alzheimer's disease and related dementias affect over 55 million people worldwide and are one of the most pressing public health challenges. Age-related hearing loss has emerged as a strong predictor of Alzheimer's disease and related dementias risk, raising the possibility that auditory dysfunction may serve as an early biomarker. While the causal nature of the relationship remains uncertain, treating hearing loss, or addressing a shared underlying mechanism, may improve quality of life and slow symptom progression in at-risk individuals. Current animal models of Alzheimer's disease largely focus on rare familial mutations, limiting their ability to capture the genetic and phenotypic heterogeneity of late-onset disease. To explore broader genetic contributions and potential links between hearing and cognition, we leveraged data from the International Mouse Phenotyping Consortium, a large-scale resource that provides standardized phenotyping across thousands of knockout mouse lines. Genes with abnormal auditory phenotypes were more likely to display behavioral abnormalities compared to genes without auditory involvement. Although other sensory modalities such as vision also showed associations with behavioral traits, the links to auditory dysfunction were stronger. Furthermore, higher auditory brainstem response thresholds correlated with the number of behavioral abnormalities across genotypes. Gene Ontology enrichment analyses of genes with auditory and behavioral phenotypes revealed distinct biological processes potentially linking sensory decline and cognitive vulnerability. These findings highlight candidate genes and molecular pathways connecting age-related hearing loss and Alzheimer's disease and related dementias, provide alternative genetic models that better reflect disease complexity, and suggest new avenues for early detection and intervention.
During pregnancy, estrogen levels rise dramatically, but quickly drop to prepartum levels following birth, and remain suppressed until ovulation resumes. This "postpartum estrogen withdrawal" state has been linked to changes in the brain and behavior in humans and rodents. Previous research has demonstrated that following a hormone-simulated pseudopregnancy (HSP), an experimental model of postpartum estrogen withdrawal, female mice show increased anxiety-like behaviors and decreased social motivation. Further, these behavioral changes occur concurrently with an increase in ΔFOSB, a transcription factor associated with stable long-term plasticity, in the nucleus accumbens core. To test whether this increase in ΔFOSB is required for these behavioral changes, we used a viral-mediated gene transfer approach to prevent ΔFOSB-mediated transcription in the NAcC during HSP and found that it reduced the high-anxiety behavioral phenotype in estrogen-withdrawn females. However, preventing ΔFOSB-mediated transcription had little effect on social motivation. Together, these results suggest that postpartum estrogen withdrawal increases ΔFOSB in the NAc core to impact anxiety-like behaviors, but not social motivation, following estrogen withdrawal.
Mouse models are an essential tool for understanding behavior and disease states in neuroscience research. While genetic and sex-specific effects have been reported in many neurodegenerative and psychiatric illnesses, these factors may also alter baseline neuroanatomical features of mice. This raises the question of whether the observed changes are related to the disease being studied (i.e., pathological differences) or if there are baseline strain or sex differences that may predispose animals to different responses. Over the past decade, tremendous effort has been made to map neural architecture at various scales; however, the complex relationships, including identifying genetic and sex-specific differences in brain structure and function, remain understudied. To bridge this gap, we used C57BL/6J and DBA/2J mice, two of the most widely used inbred mouse strains in neuroscience research, to investigate strain and sex-specific features of the brain connectome in awake animals using magnetic resonance imaging (MRI). By combining resting-state functional MRI and diffusion MRI, we found that the motor, sensory, limbic, and salience networks exhibit significant differences in both functional and structural domains between C57BL/6J and DBA/2J mice. Further, functional and structural properties of the brain were significantly correlated in both strains. Our results underscore the importance of considering these baseline differences when interpreting brain-behavior interactions in mouse models of human disorders.
Large-scale human genetic studies implicate multiple genes that regulate protein ubiquitination in autism spectrum disorder (ASD). De novo loss-of-function mutations in the gene CULLIN3 (CUL3) are implicated in autism and intellectual disability (ID). CUL3 is an essential component of an E3 ubiquitin ligase complex required for ubiquitination of substrates, often a signal for proteasomal degradation. Homozygous deletion of Cul3 is embryonically lethal. Recent studies show heterozygous deletion of Cul3 results in phenotypes with some face validity for autism in constitutive and conditional Cul3 heterozygotes. To understand the function of Cul3 in late postnatal development and function in the brain, we crossed mice expressing Cre-recombinase under the control of the CaMKII alpha promoter with conditional (floxed) Cul3 mice that resulted in viable homozygotes. In this study, we demonstrate that delayed postnatal deletion of Cul3 in predominantly forebrain excitatory neurons leads to robust behavioral differences across multiple behaviors. Cul3 conditional homozygotes show repetitive jumping, reduced marble burying, increased locomotion, impaired motor coordination, and increased hindlimb clasping. We were successfully able to replicate most of these findings in an independent cohort. Our future studies are aimed at gaining mechanistic insights into Cul3 function in the adult brain.
Cannabis use is a growing public health concern due to its neuropsychiatric consequences and potential epigenetic effects. This study investigated the methylation status of the DAT1 dopamine transporter gene in individuals with cannabis use disorder (CUD) and examined associations with personality traits. A total of 490 male participants (212 with CUD and 278 controls) were assessed using the NEO Five-Factor Inventory (NEO-FFI) and the State-Trait Anxiety Inventory (STAI). DNA methylation levels at 33 CpG sites within the DAT1 promoter region were quantified through methylation-specific PCR and sequencing. Although no significant group differences were found in overall methylation levels, logistic regression revealed significant associations between methylation status and personality dimensions. CUD was linked to higher neuroticism and openness, lower agreeableness and conscientiousness, and elevated anxiety scores. Importantly, reduced DAT1 methylation was a significant predictor of CUD. These findings underscore the interplay between personality, gene regulation, and addiction, supporting a role for epigenetic mechanisms in the development and maintenance of substance use disorders. Future research should explore site-specific CpG alterations and their longitudinal impact on neurobehavioral outcomes.
To optimize health, organisms must coordinate energy intake and expenditure and apportion related behaviors to appropriate times of day. In the fruit fly, Drosophila melanogaster, the SIFamide (SIFa) neuropeptide impacts multiple behavioral outputs important for energy regulation, including reproductive activity, sleep, and feeding. SIFa-expressing neurons receive convergent inputs from circadian and homeostatic brain regions and extend elaborate projections throughout the central nervous system. Consistent with this distribution pattern, the SIFa receptor (SIFaR) is widely expressed in the brain and ventral nerve cord, providing the anatomical substrate for SIFa signaling to influence a broad range of neuronal functions. To further explore the pleiotropic role of SIFa signaling in behavioral control, we have assessed survival, locomotor activity, sleep, and feeding in SIFaR mutant flies, as well as in flies with RNA interference-induced reduction of SIFaR expression. We find that loss of SIFaR has a complex effect on fly survival that is background- and allele-specific. However, outcrossed SIFaR mutant flies are viable, enabling monitoring of adult behavior. These flies exhibit elevated locomotor activity, reduced sleep, and increased feeding at specific times of day. We also find that SIFaR mutations drastically decrease starvation resistance. These results suggest a prominent role for SIFaR in integrating homeostatic and circadian information to coordinate the magnitude and timing of energy balance-related behaviors.
While observational studies have linked birth weight to developmental-behavioral disorders, establishing genetic correlations and causal relationships remains challenging due to potential confounding factors. In this study, we assessed genetic correlations between birth weight and developmental-behavioral disorders using linkage disequilibrium score regression (LDSC), identified pleiotropic loci and genes through Pleiotropy Analysis under Composite Null Hypothesis (PLACO), and investigated causal relationships via Mendelian randomization (MR) analysis. The results revealed significant negative genetic correlations between ADHD and birth weight (fetal: rg = -0.087, 95% CI -0.134 to -0.040; maternal: rg = -0.088, 95% CI -0.139 to -0.0337; maternal effect: rg = -0.107, 95% CI -0.183 to -0.030). We identified 41 pleiotropic genes enriched in cardiovascular, brain, and liver tissues, and 122 pleiotropic loci through eQTL integration. However, MR analysis showed no causal associations between birth weight and developmental behavioral disorders. These analyses establish both shared genetic etiology and biological pleiotropy underlying birth weight and developmental-behavioral disorder associations.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with both genetic and environmental contributions. Previous work identified a de novo mutation in the dopamine transporter (DAT T356M) in an autism proband that results in profound behavioral changes when expressed homozygously in mice. Since complex human genetics are more likely to be present as heterozygous (single allele) mutations, we characterized mice that were heterozygous for the mutation. Both male and female DAT T356M+/- mice exhibited hyperactivity but normal habituation to novel environments. The difference in hyperactivity compared to wild-type littermates was dramatically smaller than previously reported in homozygous animals. Other behavioral alterations were sex-specific, with only male heterozygous mice exhibiting greater repetitive behaviors and impaired spatial learning in the Barnes maze. Sensorimotor gating measured by prepulse inhibition of the startle response was largely unchanged in both sexes. Motor performance on the rotarod showed opposing effects, with male heterozygotes showing decreased latency to fall while females demonstrated increased latency (i.e., enhanced performance). These findings suggest that even a single copy of the DAT T356M variant can impact behavior in a sex-specific manner. The identification of intermediate phenotypes makes these mice an appropriate model for future studies examining how environmental factors might interact with genetic susceptibility to influence autism-relevant behaviors, particularly in the context of dopaminergic dysfunction.
Investigating the spatiotemporal patterns of gene expression in the brain is a critical step toward unraveling the molecular mechanisms underlying social behavior. While significant progress has been made in identifying neurogenomic states associated with diverse social contexts and their biological pathways, genomic studies often yield hundreds of candidate genes. This necessitates pinpointing key genes that drive behavior for more targeted research. In this study, we examine how the spatiotemporal expression of selected candidate genes varies between mating and social contexts. Building on insights from previous transcriptomic analyses, we identified promising gene candidates and examined their expression patterns in the female guppy brain (Poecilia reticulata). We evaluated these patterns within the brain's social decision-making network at 10 and 30 min post-exposure to either a mating or social stimulus. Genes such as gria1a, thap6, gria2, and agap3 exhibited the most pronounced differences in expression between mating and social contexts, suggesting their potential roles in regulating mating behavior. Employing a novel hierarchical coexpression network analysis, we captured the intricate gene expression changes underlying behavior. This approach allowed us to visualize distinct patterns of brain activity, revealing that the response to mating stimuli was localized to anterior nuclei, whereas the response to social stimuli was more evenly distributed across the social decision-making network. Additionally, we observed greater variability in gene expression between social and mating contexts at the 10-min time point.
Heritability of cognitive function is estimated to be 50%-80%. Genome-wide association studies (GWASs) have identified multiple cognitive function-associated loci, primarily in the European population. However, those in Asian populations, particularly in individuals of Japanese ancestry, remain limited. Hence, this GWAS aimed to identify cognitive function-associated genetic loci in elderly individuals of Japanese ancestry. Herein, 2571 elderly participants from the Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study were included. Their cognitive function was assessed using the Japanese version of the Mini-Mental State Examination (MMSE), and both binary and continuous MMSE scores were analysed. Genotyping was performed using the Affymetrix Axiom Japonica Array v2, and imputation was conducted with 3.5KJPNv2 and 1KGP3. Statistical analyses were performed using FastGWA-GLMM and FastGWA for binary and continuous MMSE scores, respectively. Although no genome-wide significant loci were identified using binary MMSE values, the following two were detected using continuous MMSE values: rs77877360 (20p12.1) near BANF2 and SNX5 and rs9460729 (6p22.3) near PRL and HDGFL1. Additionally, functional annotation suggested the involvement of these loci in pathways related to cognitive function, including chromatin structure regulation, neuroinflammation, and iron metabolism. Notably, SNX5, identified through chromatin-interaction mapping, has been implicated in neurodegenerative processes, particularly in Parkinson's disease. The findings of this study provide preliminary genome-wide evidence suggesting a genetic predisposition to impaired cognitive function in elderly Japanese individuals.
The amygdala participates in the processing of stimulus signals from stimuli and the coordination of the physiological and behavioral responses. The sexually dimorphic structure of the amygdala also contributes to sex-specific molecular and functional profiles. The present study compares the response of the amygdala molecular mechanisms to different environmental stimuli between sexes. The amygdala of female and male pigs was profiled under control, immunostimulation, and the metabolic stimulus of fasting using RNA-sequencing. Differential expression analysis (False Discovery Rate -adjusted p value < 0.05) identified 958 genes affected by stimulus and 504 genes affected by sex within treatments. The functional categories presenting a predominance of differentially expressed genes included the synaptic vesicle cycle pathway, vascular smooth muscle contraction pathway, epithelial cell proliferation process, chemokine signaling, and apoptosis. Network analysis revealed hub genes, including Stx1a, Cplx1, Clam3, and Myh11, among the gene modules susceptible to stimuli. The regulatory element SUZ12 was associated with differential gene expression between stimuli in both sexes, whereas RELA and IRF1 were uniquely detected in males and females, respectively. The findings from the multifaceted approach provide genomic leads to investigating interventions that can mitigate the effects of stimuli on the amygdala function.
Major depressive disorder is a prevalent and debilitating psychiatric illness that produces significant disability. Clinical data suggest that the pathophysiology of depression is due, in part, to a dysregulation of inflammation and glutamate levels in the brain. The systemic administration of lipopolysaccharide (LPS) has been shown to induce depressive-like behaviors in mice. Dapagliflozin (DPG), a sodium-glucose cotransporter-2 inhibitor (SGLT2i), used to treat type 2 diabetes, has been reported to produce neuroprotective effects in various animal models. This study aimed to determine the efficacy of DPG (0.5 mg/kg) to decrease LPS-induced depressive-like behaviors in mice. Thirty-six male mice were divided into four groups (n = 9): Saline (normal saline, 1 mL/kg, i.p., for 14 days), LPS (saline for 7 days followed by 1 mg/kg of LPS, i.p.), DPG (0.5 mg/kg, oral gavage for 14 days), and LPS and DPG (DPG alone for 7 days, followed by LPS and DPG for another 7 days). The forced swim (FST) and tail suspension tests (TST), putative animal models of depression, were conducted at the end of the study. After euthanization, brain tissues and blood samples were collected. The expression of glutamate transporter 1 (GLT-1), solute carrier family 7-member 11 (SLC7A11), and nuclear factor kappa β (NF-κB) mRNA was determined using q-PCR. LPS induced depressive-like behavior and significantly increased mRNA levels of GLT-1, SLC7A11, and NF-κB. DPG alone also affected baseline performance in the TST. Furthermore, DPG significantly decreased the LPS-induced changes, suggesting that it may alleviate LPS-induced depressive behaviors by modulating glutamate homeostasis and inflammatory pathways.
