Biology subjects

Banasr, M.

Publications and source records attributed to Banasr, M..

14 recordsLinked to original sources

bioRxiv2026

The Aging Brain Matrix: Cross-Species Evidence Linking FREM3 to Brain and Cognitive Aging

The human extracellular-matrix-related FREM3 gene is strongly age-dependent, enriched in age-sensitive excitatory long-range-projecting neurons, and implicated in neurodegenerative diseases. To establish the first translationally relevant causal evidence for the role of FREM3 in brain structure and cognition, we developed an excitatory-neuron-specific Frem3 conditional knockout mouse model (Frem3-cKO) and computed genetically regulated expression of FREM3 (FREM3-GReX) in humans, enabling convergent neurostructural and cognitive characterizations. Frem3-cKO mice showed widespread lower global and regional brain volume in middle age vs young adulthood, consistent with drastic age-dependent volume loss absent in wildtype mice. These effects were strongest in cognitively relevant cortical regions and paralleled by lower cognitive performance. In humans, lower FREM3-GReX was associated with lower total surface area, which further mediated an indirect link to lower cognitive performance across multiple age-sensitive domains. We provide the first translationally relevant cross-species evidence supporting a key role for FREM3/Frem3 in maintaining brain and cognitive health across aging.

neuroscience↗

bioRxiv2026

Dual Roles of Interferon-γ Receptor in Somatostatin Interneurons at Baseline and During Inflammation

Background: Neuropsychiatric disorders such as major depressive disorder show converging evidence of gamma-aminobutyric acid (GABA) dysfunction, including consistent reductions in somatostatin (SST) interneuron markers. SST interneurons are selectively vulnerable to inflammation, yet the underlying mechanisms remain unclear. Interferon-gamma (IFN-{gamma}), a pro-inflammatory cytokine implicated in mood and anxiety disorders, signals through the IFN-{gamma} receptor (IFNGR), which is expressed in neurons. We tested whether IFNGR signaling in SST interneurons regulates anxiety-like and cognitive behavior and prevents inflammation-induced molecular deficits. Methods: We generated mice with conditional deletion of IFNGR from SST cells and assessed anxiety-like behavior using elevated plus maze and working memory using Y-maze at baseline and after lipopolysaccharide (LPS) induced inflammation. Expression of SST-related, neurotrophic, synaptic, and glial markers was quantified. Results: At baseline and after LPS-induced inflammation, IFNGR deletion in SST cells increased anxiety-like behavior without affecting working memory. In control mice, LPS reduced Sst (p=0.0006), neuropeptide Y (Npy) (p=0.0022), brain-derived neurotrophic factor (Bdnf) (p<0.0001), and synapsin 1 (Syn1) (p=0.0150); these reductions were not significant in mice lacking IFNGR in SST cells. Knockouts also showed lower baseline Bdnf, Syn1, Gephyrin (Gphn), and allograft inflammatory factor 1 (Aif1, encoding Iba1) than controls. Conclusions: IFNGR signaling in SST cells plays a dual role: supporting normal behavior and molecular homeostasis while mediating LPS-induced molecular deficits. These findings link immune signaling to the GABAergic dysfunction implicated in major depressive disorder and suggest IFNGR signaling in SST cells may regulate cortical microcircuit integrity at baseline and during inflammatory challenge.

neuroscience↗

bioRxiv2025

Neuronal and Astrocytic Activity Changes Induced by Acute and Chronic Stress

Exposure to acute, repeated, or chronic stress elicits a spectrum of cellular changes ranging from adaptive to maladaptive, including in the prefrontal cortex (PFC) where both neurons and astroglia undergo morphological, cellular and molecular remodeling. However, whether these alterations translate into altered cell activity and neuron-astroglia communication and how such changes evolve with recurrent stress or chronic stress exposure remains poorly understood. To address these questions, we used dual-color in vivo fiber photometry to longitudinally record PFC neuronal and astroglial calcium (Ca{superscript 2}) signals in the same mice during a brief (tail pinch), sustained (immobilization) acute stress, repeated homotypic stress across weeks, and unpredictable chronic mild stress (UCMS), tracking of same cellular network across time. We found that acute stressors elicited coordinated increases in neuronal and astroglial Ca{superscript 2} activity and enhanced their Ca2+ signal coupling. Repeated intermittent stress induced comparable per-cell-type responses but progressively strengthened coupling, suggesting adaptation. We also demonstrated that this trajectory is reversed under UCMS; neuronal Ca{superscript 2} reactivity to stress challenge was sensitized whereas astroglial reactivity was blunted. This was associated with a weakened intercellular coupling (-3.5 fold) and astroglia became progressively hyporesponsive to neuronal drive. UCMS-induced neuron-astroglia functional coupling impairment coincided with the onset of anhedonia- and anxiety-like behavioral deficits. These findings position impaired neuron-astroglial functional coupling as a potential substrate of stress-induced cortical dysfunction that may distinguish adaptive from maladaptive stress responses, offering a mechanistically tractable target for intervention in stress-related psychiatric disease such as depression, where dysfunction in both cell types has been consistently reported.

neuroscience↗

bioRxiv2023

Prefrontal Cortex Astroglia Modulate Anhedonia-like Behavior

Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.

neuroscience↗

bioRxiv2023

Lifespan Changes in Brain Structure and Cognitive Performance Associated with Normal Aging in Mice

IntroductionAs the population skews toward older age, elucidating mechanisms underlying human brain aging becomes imperative. Structural MRI has facilitated non-invasive investigation of lifespan brain morphology changes, yet this domain remains uncharacterized in rodents despite increasing use as models of disordered human brain aging. MethodsYoung (2m, n=10), middle-age (10m, n=10) and old (22m, n=9) mice were utilized for maturational (young vs. middle-age) and aging-related (middle-age vs. old mice) comparisons. Regional brain volume was averaged across hemispheres and reduced to 32 brain regions. Pairwise group differences in regional volume, residualized for total brain volume, and associations between volume and cognitive performance on the Y-maze task were tested. General linear models with total brain volume as a covariate, and logistic regression for sample wide associations were employed respectively, correcting for multiple comparisons. Structural covariance networks were generated using the R package igraph. Group differences in network centrality (degree), integration (mean distance), and segregation (transitivity, modularity) were tested across network densities (5-40%), using 5,000 (1,000 for degree) permutations with significance criteria of p<0.05 at [≥]5 consecutive density thresholds. ResultsWidespread significant maturational changes in volume occurred in 18 brain regions, including considerable loss in isocortex regions and increases in brainstem regions and white matter tracts. The aging-related comparison yielded 6 significant changes in brain volume, including further loss in isocortex regions and increases in white matter tracts. No significant volume changes were observed across either comparison for subcortical regions. Additionally, smaller volume of the anterior cingulate area ({chi}2=2.325, pO_SCPLOWBHC_SCPLOW=0.044) and larger volume of the hippocampal formation ({chi}2=-2.180, pO_SCPLOWBHC_SCPLOW=0.044) were associated with poorer cognitive performance. Maturational network comparisons yielded significant degree changes in 9 regions, but no aging related changes, aligning with network stabilization trends in humans. Maturational decline in modularity occurred (24-29% density), mirroring human trends of decreased segregation in young adulthood, while mean distance and transitivity remained stable. Conclusions/ImplicationsThese findings offer a foundational account of age effects on brain volume, structural brain networks, and cognition in mice, informing future work in facilitating translation between rodent models and human brain aging.

neuroscience↗

bioRxiv2021

Behavioral and Neurostructural changes associated with Chronic Amygdala Hyperactivation

BackgroundThe amygdala (AMY) is a key brain region of the limbic system that plays a critical role in emotion processing and stress response. Functional magnetic resonance imaging (fMRI) studies identified abnormal AMY activation in psychiatric illnesses including major depressive disorder (MDD). Stress exposure is a major precipitating factor of MDD episodes which are associated with AMY hyperactivity. Preclinical studies using of pharmacologic, opto- and chemogenetic approaches to activate AMY neurons have consistently demonstrated that acute AMY hyperactivation induces anxiety-like behaviors in mice. However, it remains unknown if chronic hyperactivation of the amygdala (cHOA) is sufficient to induce chronic stress-like deficits or is a susceptibility factor for chronic stress-induced behavioral, volumetric and synaptic deficits. MethodsUsing designer receptor exclusively activated by designer drug (DREADD) approach, basolateral amygdala (BLA) neurons of Camk2a-cre mice infected with a virus driving the expression of the Gq-coupled DREADD were activated with clozapine-N-oxide (in drink water for 5 weeks). Mice were then exposed to chronic restraint stress (CRS; 1X/day for 1hr) for 2 weeks. All mice were behaviorally assessed in the Phenotyper (PT), and sucrose consumption tests (SCT) each week and in the novelty supressed feeding (NSF, once at the end of the experiment). Animals were then perfused for ex vivo-MRI and puncta density analysis. ResultsWe found that mice with cHOA displayed a progressive increase in baseline anxiety-like deficits in the PT test and slightly more marked deficits following CRS compared to controls, but not statistically different from animals subjected to CRS alone. Also, cHOA did not exacerbate CRS effect in the NSF. No significant cAH effect was found in the SCT before or after CRS. MRI analysis revealed no statistical charges between groups, while increased synaptic puncta density was found in cHOA mice subjected to CRS compared to cHOA or CRS alone. ConclusionWe demonstrate that cAH is sufficient to induce anxiety and may exacerbate CRS effects on anxiety and synaptic measures. Results also suggest that cHOA was not sufficient to induce depressive-like behavior and was not a vulnerability factor for stress-induced depressive-like behavior in mice. Altogether, our findings imply that a strong causal link between AMY hyperactivity and elevated anxiety, but not depressive-like behaviors and provide critical information to clinical research focused on using AMY activity level as a biomarker in stress-related illnesses.

neuroscience↗

bioRxiv2021

Dynamic behavioral and molecular changes induced by chronic stress exposure in mice

Depression is a leading cause of disabilities around the world, and the underlying mechanisms involved in its pathophysiology are broad and complex. Exposure to chronic stress is a risk factor for developing depressive-symptoms and contributes to cellular and molecular changes precipitating the emergence of symptoms. In the brain, excitatory neurons, inhibitory interneurons and supporting astroglial cells are all sensitive to chronic stress exposure and are known to be impaired in depression. Using an animal model of chronic stress, we assessed the impact of variable durations of chronic stress on the emergence of behavioral deficits and associated molecular changes in the prefrontal cortex (PFC), brain region highly sensitive to stress and impaired in depression. Mice were exposed to up to 35 days of chronic restraint stress and were assessed weekly on behavioral tests measuring anxiety and anhedonia. PFC Protein and RNA levels of specific markers of excitatory, inhibitory synapses and astroglia were quantified using western blot and qPCR, respectively. Correlation and integrative network analyses were used to investigated the impact of chronic stress on the different compartments. Results showed that chronic stress induces anxiety-like behaviors within 7 days, while anhedonia-like behaviors were observed only after 35 days. At the molecular level, alterations of many markers were observed, in particular with longer exposure to chronic stress. Finally, correlation analyses and integrative network analyses revealed that male and female mice react differently to chronic stress exposure and that some markers seem to be more correlated to behaviors deficits in males than in females. Our study demonstrate that chronic induces a dynamic changes that can be observed at the behavioral and molecular levels, and that male and female mice, while exhibiting similar symptoms, have different underlying pathologies.

neuroscience↗

bioRxiv2021

Chronic Stress Alters Astrocyte Morphology in Mouse Prefrontal Cortex

BackgroundNeuromorphological changes are consistently reported in the prefrontal cortex (PFC) of patients with stress-related disorders and in rodent stress models, but the effects of stress on astrocyte morphology and potential link to behavioral deficits are relatively unknown. MethodsTo answer these questions, transgenic mice expressing green fluorescent protein (GFP) under the glial fibrillary acid protein (GFAP) promotor were subjected to 7, 21 or 35 days of chronic restraint stress (CRS). CRS induced behavioral effects on anhedonia- and anxiety-like behaviors were measured using the sucrose intake and the PhenoTyper tests, respectively. PFC GFP+ or GFAP+ cells morphology was assessed using Sholl analysis and associations with behavior were determined using correlation analysis. ResultsCRS-exposed male and female mice displayed anxiety-like behavior at 7, 21 and 35 days and anhedonia-like behavior at 35 days. Analysis of GFAP+ cell morphology revealed significant atrophy of distal processes following 21 and 35 days of CRS. CRS induced similar decreases in intersections at distal radii for GFP+ cells, accompanied by increased proximal processes. In males, the number of intersections at the most distal radius step significantly correlated with anhedonia-like behavior (r=0.622, p<0.05) for GFP+ cells and with behavioral emotionality calculated by z-scoring all behavioral measured deficits (r=-0.667, p<0.05). Similar but not significant correlations were observed in females. No correlation between GFP+ cell atrophy with anxiety-like behavior was found. ConclusionChronic stress exposure induces a progressive atrophy of cortical astroglial cells, potentially contributing to maladaptive neuroplastic and behavioral changes associated with stress-related disorders.

animal behavior and cognition↗

bioRxiv2020

Reduced anterior cingulate cortex volume induced by chronic stress correlates with increased behavioral emotionality and decreased synaptic puncta density

Clinical and preclinical studies report that chronic stress induces behavioral deficits as well as volumetric and synaptic alterations in corticolimbic brain regions including the anterior cingulate cortex (ACC), amygdala (AMY), nucleus accumbens (NAc) and hippocampus (HPC). Here, we aimed to investigate the volumetric changes associated with chronic restraint stress (CRS) and link these changes to the CRS-induced behavioral and synaptic deficits. We first confirmed that CRS increases behavioral emotionality, defined as collective scoring of anxiety- and anhedonia-like behaviors. We then demonstrated that CRS induced a reduction of total brain volume which negatively correlated with behavioral emotionality. Region-specific analysis identified that only the ACC showed significant decrease in volume following CRS (p<0.05). Reduced ACC correlated with increased behavioral emotionality (r=-0.56; p=0.0003). Although not significantly altered by CRS, AMY and NAc (but not the HPC) volumes were negatively correlated with behavioral emotionality. Finally, using structural covariance network analysis to assess shared volumetric variances between the corticolimbic brain regions and associated structures, we found a progressive decreased ACC degree and increased AMY degree following CRS. At the cellular level, reduced ACC volume correlated with decreased PSD95 (but not VGLUT1) puncta density (r=0.35, p<0.05), which also correlated with increased behavioral emotionality (r=-0.44, p<0.01), suggesting that altered synaptic strength is an underlying substrate of CRS volumetric and behavioral effects. Our results demonstrate that CRS effects on ACC volume and synaptic density are linked to behavioral emotionality and highlight key ACC structural and morphological alterations relevant to stress-related illnesses including mood and anxiety disorders. HighlightsO_LIChronic restraint stress (CRS) decreases anterior cingulate cortex (ACC) volume C_LIO_LIACC and amygdala (AMY) volumes negatively correlate with behavioral emotionality C_LIO_LICRS decreased the strength and degree of the ACC structural covariance network C_LIO_LICRS increased the strength and degree of the AMY structural covariance network C_LIO_LIPSD95 puncta density correlates with behavioral emotionality and ACC volume. C_LI

neuroscience↗

bioRxiv2020

Chronic stress induces coordinated cortical microcircuit cell type transcriptomic changes consistent with altered information processing

Major depressive disorder (MDD) is associated with altered GABAergic and glutamatergic signalling, suggesting altered excitation-inhibition balance (EIB) in cortical mood- and cognition-regulating brain regions. Information processing in cortical microcircuits involves regulation of pyramidal (PYR) cells by Somatostatin-(SST), Parvalbumin-(PV), and Vasoactive intestinal peptide-(VIP) expressing interneurons. Human and rodent studies suggest that impaired PYR-cell dendritic morphology and decreased SST-cell function may mediate altered EIB in MDD. However, knowledge of co-ordinated changes across microcircuit cell types is virtually absent. We thus investigated the co-ordinated transcriptomic effects of UCMS on microcircuit cell types in the medial prefrontal cortex. C57Bl/6 mice, exposed to unpredictable chronic mild stress (UCMS) or control housing for five weeks were assessed for anxiety- and depressive-like behaviours. Microcircuit cell types were laser-microdissected and processed for RNA-sequencing. UCMS-exposed mice displayed predicted elevated behavioural emotionality. Each microcircuit cell type showed a unique transcriptional signature after UCMS. Pre-synaptic functions, oxidative stress response, metabolism, and translational regulation were differentially dysregulated across cell types, whereas nearly all cell types showed down-regulated post-synaptic gene signatures. At the microcircuit level, we observed a shift from distributed transcriptomic co-ordination across cell types in controls towards UCMS-induced increased co-ordination between PYR-, SST- and PV-cells, and a hub-like role for PYR-cells. Lastly, we identified a microcircuit-wide co-expression network enriched in synaptic, bioenergetic, and oxidative stress response genes that correlated with UCMS-induced behaviours. Together, these findings suggest cell-specific deficits, microcircuit-wide synaptic reorganization, and a shift in cortical EIB mediated by increased co-ordinated regulation of PYR-cells by SST- and PV-cells.

neuroscience↗

bioRxiv2020

Prophylactic efficacy of riluzole against anxiety- and depressive-like behaviors in two rodent stress models

BackgroundChronic stress-related illnesses, such as major depressive disorder and post-traumatic stress disorder share symptomatology, including anxiety, anhedonia, and helplessness. Across disorders, neurotoxic dysregulated glutamate (Glu) signaling may underlie symptom emergence. Current first-line antidepressant drugs, which do not directly target Glu signaling, fail to provide adequate benefit for many patients and are associated with high relapse rates. Riluzole modulates glutamatergic neurotransmission by increasing metabolic cycling and modulating signal transduction. Clinical studies exploring riluzoles efficacy in stress-related disorders have provided varied results. However, the utility of riluzole for treating specific symptom dimensions or as a prophylactic treatment has not been comprehensively assessed. MethodsWe investigated whether chronic prophylactic riluzole (~12-15mg/kg/day p.o.) could prevent the emergence of behavioral deficits induced by unpredictable chronic mild stress (UCMS) in mice. We assessed: i) anxiety-like behavior using the elevated-plus maze, open field test, and novelty-suppressed feeding, ii) mixed anxiety/anhedonia-like behavior in the novelty-induced hypophagia test and, iii) anhedonia-like behavior using the sucrose consumption test. Z-scoring summarized changes across tests measuring similar dimensions. In a separate learned helplessness (LH) cohort, we investigated whether chronic prophylactic riluzole treatment could block the development of helplessness-like behavior. ResultsUCMS induced an elevation in anhedonia-like behavior, and overall behavioral emotionality that was blocked by prophylactic riluzole. In the LH cohort, prophylactic riluzole blocked the development of helplessness-like behavior. ConclusionThis study supports the utility of riluzole as a prophylactic medication for preventing anhedonia, and helplessness symptoms associated with stress-related disorders.

pharmacology and toxicology↗

bioRxiv2020

Chronic stress exacerbates acute stress-induced neuronal activation in the anterior cingulate cortex and ventral hippocampus that correlates with behavioral deficits in mice

Altered activity of corticolimbic brain regions is a hallmark of stress-related illnesses, including mood disorders, neurodegenerative diseases, and substance abuse disorders. Acute stress adaptively recruits brain region-specific functions for coping, while sustained activation under chronic stress may overwhelm feedback mechanisms and lead to pathological cellular and behavioral responses. The neural mechanisms underlying dysregulated stress response and how they contribute to behavioral deficits are poorly characterized. Here, we tested whether prior exposure to chronic restraint stress (CRS) or unpredictable chronic mild stress (UCMS) in mice could alter neuronal response to acute stress and whether these changes are associated with chronic stress-induced behavioral deficits. More specifically, we assessed neuronal activation indexed by c-Fos+ cell counts in 24 stress- and mood-related brain regions, and determined if changes in acute stress-induced neuronal activation were linked to chronic stress-induced behavioral impairments. Results indicated that CRS and UCMS led to convergent physiological and anxiety-like deficits, whereas cognition was impaired only in UCMS mice. CRS and UCMS exposure exacerbated neuronal activation in response to an acute stressor in anterior cingulate cortex (ACC) area 24b and ventral hippocampal (vHPC) CA1, CA3, and subiculum. In dysregulated brain regions, levels of neuronal activation were positively correlated with principal components capturing variance across widespread behavioral alterations relevant to stress-related disorders. Our data supports an association between a dysregulated stress response, altered corticolimbic excitation/inhibition balance, and the expression of maladaptive behaviors. HighlightsO_LIChronic stress models produce variable profiles of physiological deficits, anxiety-like behavior, and impaired cognition C_LIO_LIAcute stress-induced activation of ACC A24b & vHPC is exacerbated by prior chronic stress exposure C_LIO_LIIn regions dysregulated by chronic stress, altered neuronal activation is positively correlated with behavioral deficits C_LI

neuroscience↗

bioRxiv2018

Repeated assessment of anxiety-like behavior in mice: a new tool with increased reliability and consistency.

Stress-related illnesses such as major depressive and anxiety disorders are characterized by maladaptive responses to stressful life events. Chronic stress-based animal models have provided critical insight into the understanding of these responses. Currently available assays measuring chronic stress-induced behavioral states in mice are limited in their design (short, not repeatable, sensitive to experimenter-bias) and often inconsistent. Using the Noldus PhenoTyper apparatus, we identified a new readout that repeatedly assesses behavioral changes induced by chronic stress in two mouse models i.e. chronic restraint stress (CRS) and chronic unpredictable mild stress (UCMS). The PhenoTyper test consists of overnight monitoring of animals behavior in home-cage setting before, during and after a 1hr light challenge applied over a designated food zone. We tested the reproducibility and reliability of the PhenoTyper test in assessing the effects of chronic stress exposure, and compared outcomes with commonly-used tests. While chronic stress induced heterogeneous profiles in classical tests, CRS- and UCMS-exposed mice showed a very consistent response in the PhenoTyper test. Indeed, CRS and UCMS mice continue avoiding the lit zone in favor of the shelter zone. This \"residual avoidance\" after the light challenge, lasted for hours beyond termination of the challenge, was not observed after acute stress and was consistently found throughout stress exposure in both models. Chronic stress-induced residual avoidance was alleviated by chronic imipramine treatment but not acute diazepam administration. This behavioral index should be instrumental for studies aiming to better understand the trajectory of chronic stress-induced deficits and potentially screen novel anxiolytics and antidepressants.

animal behavior and cognition↗

bioRxiv2018

Potential combined pro-cognitive, anxiolytic and antidepressant properties of novel GABAA receptor positive modulators with preferential efficacy at the α5-subunit

Altered {gamma}-aminobutyric acid (GABA) function is consistently reported in psychiatric disorders, normal aging and neurodegenerative disorders, and reduced function of somatostatin - expressing GABA interneurons is associated with both mood and cognitive symptoms. Somatostatin-neurons signal in part through 5-subunit containing GABAA receptors (5-GABAA-Rs) which are localized in brain regions implicated in emotion and cognition. We hypothesize that enhancing 5-GABAA-R activity has therapeutic potential for both mood and cognitive symptoms in stress-based and aging rodent models.\n\nWe synthesized four novel imidazobenzodiazepine (IBZD) amide ligands, tested them for positive allosteric modulation at 5-GABAA-R (5-PAM), pharmacokinetic properties, and for anxiolytic and antidepressant activities in adult mice. Pro-cognitive activity was tested in adult mice submitted to chronic stress and in old mice. Diazepam (DZP), with broad PAM activity at GABAA-Rs, was used as a control.\n\nThree novel IBZD amide ligands (GL-II-73, GL-II-74 and GL-II-75) demonstrated adequate brain penetration, affinity and 5-PAM activity, and metabolic stability for in vivo studies. GL-II-73/74/75 showed significant anxiolytic and antidepressant efficacies in adult mice. GL-II-73 and GL-II-75 significantly reversed cognitive deficits induced by stress or occurring throughout normal aging. This activity was maintained after sub-chronic administration for GL-II-73. In contrast DZP displayed anxiolytic but no antidepressant or pro-cognitive activities.\n\nWe demonstrate for the first time the potential for combined anxiolytic, antidepressant and pro-cognitive therapeutic, mediated by newly designed IBDZ amide ligands with efficacy at 5-GABAA-Rs. These results suggest a novel therapeutic approach targeting both mood and cognitive symptoms in depression and/or aging.

pharmacology and toxicology↗