Biology subjects

Solano, J. L.

Publications and source records attributed to Solano, J. L..

4 recordsLinked to original sources

bioRxiv2026

Low testosterone promotes anxiety through astrocytic mitochondrial remodelling at the nucleus accumbens blood-brain barrier

Low testosterone is linked to anxiety in men, but its causal role and underlying brain mechanisms remain unknown. Here, using outbred male rats stratified by natural variation in anxiety-like behaviour, we establish its causal endocrine contribution and uncover an astrocytic mitochondrial mechanism at the nucleus accumbens (NAc) blood-brain barrier (BBB). High-anxiety rats showed a NAc-selective increase in BBB permeability, alongside reduced astrocytic endfoot coverage, disrupted endfoot mitochondrial organisation and mitochondria-endoplasmic reticulum contacts, and lower mitofusin 2 (Mfn2). Testosterone suppression increased anxiety in low-anxiety rats, whereas physiological testosterone restoration reduced anxiety, reconfigured astrocytic mitochondrial and BBB-related transcriptional programmes, increased astrocytic endfoot coverage and Mfn2, recovering BBB permeability, with related effects in aged low-testosterone rats. NAc androgen receptor (AR) knockdown blunted behavioural and neurovascular responses, whereas NAc astrocyte-specific Mfn2 overexpression reduced anxiety. Thus, testosterone-AR signalling engages an astrocytic mitochondrial programme at the NAc neurovascular interface linking low testosterone to anxiety vulnerability.

neuroscience↗

bioRxiv2026

Early life stress exposure alters brain vasculature transcriptomic profiles in areas regulating stress resilience

Early life stress (ELS) events during sensitive postnatal time periods can recalibrate future stress responsiveness and precipitate mental disorders. Neurovascular adaptations can influence cognition, mood, and stress responses. Disruption of blood-brain barrier (BBB) integrity, which is formed by endothelial cells, astrocytes, and pericytes, has been implicated in affective disorders such as depression, which often arise from chronic stress experiences. Despite the BBB undergoing critical maturation stages during development, it remains poorly known how ELS influences brain vascular function, as previously shown for adult stress, and whether it augments BBB vulnerability to subsequent challenges. First, we took advantage of a public two-hit stress RNA-sequencing dataset and filtered for vascular enriched genes in the prefrontal cortex and nucleus accumbens, the two brain regions where BBB integrity is frequently compromised. This analysis revealed BBB-related gene ontology categories modulated by either ELS alone or its combination with adult stress. Then, using a mouse model combining ELS with chronic social defeat stress (CSDS) in adulthood, we found that ELS did not exacerbate CSDS susceptibility; instead, it increased social interactions and the likelihood of a resilient profile in both males and females. Transcriptomic profiling in our cohort further identified distinct sex- and region-specific BBB gene expression patterns associated with ELS and its interaction with CSDS. Additionally, we observed a reduction of corticosterone levels, the primary stress hormone, following CSDS. Altogether, these results indicate that ELS modulates stress responses when facing emotional challenges in adulthood, possibly through long-lasting changes of BBB function via the glucocorticoid system. HighlightsO_LIRNA-seq vascular filtering reveals BBB distinct ontology categories for ELS and AS C_LIO_LIELS increases the likelihood of a high social and resilient profile. C_LIO_LIPericytes gene expression associated to resilience is sex- and region-specific. C_LIO_LICORT response desensitizes after adult CSDS in both sexes. C_LI

neuroscience↗

bioRxiv2023

Environmental enrichment and physical exercise prevent stress-induced behavioral and blood-brain barrier alterations via Fgf2

Chronic stress can promote loss of blood-brain barrier (BBB) integrity leading to passage of circulating inflammatory mediators in mood-regulating brain areas and establishment of depressive behaviors. Conversely, neurovascular adaptations favoring resilience to stress exposure remain undetermined. Here, we report that environmental enrichment dampens stress-induced loss of endothelial tight junction protein Claudin-5 (Cldn5) along with anxiety- and depression-like behaviors in mice via an increase in fibroblast growth factor 2 (Fgf2). Treatment of mouse and human endothelial cells with Fgf2 preceding an immune challenge with the proinflammatory cytokine TNF, elevated after chronic stress and in depression, reduces BBB dysfunction, and altered cell signaling. Coping with voluntary physical exercise also protects the BBB from stress deleterious effects by increasing Fgf2 preventing Cldn5 loss, exacerbated inflammation, and social avoidance. Circulating FGF2 level is linked with depression severity and symptomatology in humans supporting involvement of this growth factor in mood disorders and stress-induced BBB changes.

neuroscience↗

bioRxiv2022

Chronic stress exposure alters the gut barrier: sex-specific effects on microbiota and jejunum tight junctions

Major depressive disorder (MDD) is the leading cause of disability worldwide. However, 30-50% of patients are unresponsive to commonly prescribed antidepressants, highlighting untapped causal biological mechanisms. Dysfunction in the microbiota-gut-brain axis, the bidirectional communications between the central nervous system and gastrointestinal tract that are modulated by gut microorganisms, has been implicated in MDD pathogenesis. Exposure to chronic stress disrupts blood-brain barrier integrity, still, little is known about intestinal barrier function in these conditions particularly for the small intestine where most food and drug absorption takes place. Thus, here we investigate how chronic social or variable stress, two mouse models of depression, impact the jejunum (JEJ) intestinal barrier in males and females. Mice were subjected to stress paradigms followed by analysis of gene expression profiles of intestinal barrier-related targets, fecal microbial composition, and blood-based markers. Altered microbial populations as well as changes in gene expression of JEJ tight junctions were observed depending on the type and duration of stress, with sex-specific effects. We took advantage of machine learning to characterize in detail morphological tight junction properties identifying a cluster of ruffled junctions in stressed animals. Junctional ruffling is associated with inflammation, so we evaluated if LPS injection recapitulates stress-induced changes in the JEJ and observed profound sex differences. Finally, LPS-binding protein (LBP), a marker of gut barrier leakiness, was associated with stress vulnerability in mice and translational value was confirmed on blood samples from women with MDD. Our results provide evidence that chronic stress disrupts intestinal barrier homeostasis in conjunction with the manifestation of depressive-like behaviors in a sex-specific manner in mice and possibly, human depression.

neuroscience↗