Biology subjects

Berrocoso, E.

Publications and source records attributed to Berrocoso, E..

4 recordsLinked to original sources

bioRxiv2026

Molecular signaling associated with antidepressant actions exhibits diurnal fluctuations in the prefrontal cortex and hippocampus of adult male and female mice

An increasing number of epidemiological and experimental studies have demonstrated a bidirectional relationship between mood disorders and the circadian system, with disrupted circadian rhythms contributing to depressive states, and their restoration playing a key role in antidepressants effects. In this context, we sought to examine whether key molecular targets of antidepressants exhibit diurnal regulatory patterns. Naive adult male and female C57BL/6 mice were euthanized at 3-hour intervals beginning at Zeitgeber Time 0 (ZT0), and hippocampal (HC) and medial prefrontal cortex (mPFC) tissues were collected for RT-qPCR and western blot analyses. We observed statistically significant diurnal rhythmicity in all analyzed transcripts (cFos, Arc, Nr4a1, Dusp1, Dusp5, and Dusp6) in both HC and mPFC samples, with peak expression occurring during the dark (active) phase (ZT15-18). Phosphorylation levels of TrkBY816 (tropomyosin-related kinase) and GSK3{beta}S9 (glycogen synthase kinase 3{beta}) also showed periodic rhythmicity, peaking during the light (inactive) phase. Levels of p-ERK2T185/Y187 (extracellular-signal regulated kinase) did not display rhythmicity, but peaked during the light phase in the HC, especially in males. Collectively, these findings demonstrate that antidepressant targets are subject to diurnal regulation, highlighting the importance of integrating circadian biology and time-of-day as relevant variables in the development of translationally relevant antidepressant research. HighlightsO_LIKey molecular targets of antidepressants exhibit diurnal regulation in adult mice C_LIO_LIDiurnal patterns were conserved across targets, sexes, and brain regions (HC&PFC) C_LIO_LIcFos, Arc, Nr4a1, Dusp1,5,6 mRNAs display peak expression during the dark phase C_LIO_LITrkBY816 and GSK3{beta}S9 phosphorylation peak during the light (inactive) phase C_LIO_LIAntidepressant mechanisms may be linked with circadian and sleep-wake dynamics C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/716906v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1e65e60org.highwire.dtl.DTLVardef@13e302corg.highwire.dtl.DTLVardef@1ccc25forg.highwire.dtl.DTLVardef@1ed10d3_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

The serum from critical COVID-19 patients induces proteomic changes in olfactory neuroepithelial cells that resemble post-covid neurological complications

Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as Long COVID, comprise a constellation of persistent, recurrent, or newly emerging symptoms that may endure for months or years following acute infection. Beyond respiratory impairment, PASC is characterized by a wide spectrum of extrapulmonary manifestations, among which neurological and neuropsychiatric symptoms are highly prevalent. Reported features include olfactory dysfunction with loss of smell and taste, fatigue, neuroinflammation, cognitive and memory impairment, depression, and anxiety, with some symptoms persisting up to one year post-infection. Despite increasing recognition of these complications, the molecular mechanisms underlying post-COVID neurological sequelae remain poorly defined. In this study, we employed a label-free quantitative (LFQ) proteomics approach to investigate protein alterations in olfactory neuroepithelium-derived stem cells (ONEs), a unique population of neural progenitors located in the olfactory mucosa at the interface between the respiratory system and both the peripheral and central nervous systems. Due to their anatomical exposure and susceptibility to SARS-CoV-2, ONEs represent a highly relevant translational model for exploring virus-associated neurobiological processes. ONEs derived from healthy donors were incubated with serum from either asymptomatic PCR-positive individuals (AS; n=4) or critically ill hospitalized patients (CR; n=6). Proteomic profiling revealed a distinct differential protein expression pattern in ONEs exposed to CR serum compared with AS serum. Altered pathways were associated with viral infection responses, respiratory and cardiovascular dysfunction, and notably, cerebrovascular and nervous system disorders. These findings highlight the vulnerability of ONEs to systemic factors associated with severe COVID-19 and provide molecular insight into mechanisms potentially contributing to persistent neurological sequelae in PASC. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/710460v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@12cfda5org.highwire.dtl.DTLVardef@c0636borg.highwire.dtl.DTLVardef@bf303eorg.highwire.dtl.DTLVardef@1f861e9_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

Sex differences in the impact of nerve injury on Locus Coeruleus function and behaviour in mice

Chronic pain often coexists with stress-related disorders such as anxiety and depression, with a higher prevalence in women. Rodent studies reveal significant sex differences in pain and stress-related behaviours, emphasising the need to explore underlying neurobiological mechanisms. The locus coeruleus (LC), the main noradrenergic nucleus in the brainstem, plays a crucial role in modulating pain and stress responses and exhibits sex-specific characteristics. In this study, we investigated the effects of neuropathic pain on the LC in male and female mice, focusing on sensory thresholds, emotional states, and cognitive function. Nerve injury caused immediate sensory hypersensitivity in both sexes, while depressive-like behaviours and cognitive impairments emerged only after prolonged injury. Interestingly, anxiety-like behaviours and heightened fear conditioning were exclusive to males, which correlated with specific structural and functional changes in the male LC, such as increased noradrenergic cell counts, larger somato-dendritic volume, and greater neuron excitability. In females, however, neuronal excitability was reduced. Chemogenetic inhibition of LC neurons alleviated depressive- and anxiety-like behaviours, as well as fear conditioning, but only in males. Overall, neuropathic pain induces distinct behavioural and neurobiological responses in males and females, challenging traditional views on female vulnerability to pain-induced anxiety and highlighting the need for sex-specific LC-targeted therapies.

neuroscience↗

bioRxiv2024

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors

The brainstem cell group, locus coeruleus (LC), is present across vertebrates and influences cardiorespiratory, metabolic, immune, and cognitive functions by activating in two putatively distinct firing patterns. Yet, the degree to which the LC firing rates and patterns are homogenous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

neuroscience↗