Biology subjects

Parise, E.

Publications and source records attributed to Parise, E..

7 recordsLinked to original sources

bioRxiv2026

Molecular dissection of protein complexes isolated from sections of human brain

Molecular studies of brain receptors and transporters have typically relied on recombinant systems, limiting insight into their organization in native tissue. Here, we develop nanobody-based immunoprecipitation coupled with native mass spectrometry to interrogate endogenous protein assemblies from post-mortem mouse and human brain sections. We exemplify our approach by characterizing the synaptic proteins VGluT1 and mGluR2. From a single mouse brain, we discover mGluR2/3 heterodimers, alongside mGluR2 homodimers. Considering regions of human brain heterodimeric mGluR2/3 is highly abundant in the OFC and sgACC ([~]70% and 50%, respectively) and forms regional-specific interactions with additional synaptic proteins. In a modest cohort of biobanked human tissue, associated with depression and suicide, we find increased mGluR2/3 in the OFC. Consistent with this, mice exhibit similar associations between heterodimer levels and stress-susceptibility. Overall, our approach provides a direct means for establishing molecular-behavioural links at the level of receptor organization in brain.

biochemistry↗

bioRxiv2026

A shared transcriptional network in the nucleus accumbens supports resilience to chronic stress across sex.

Although chronic stress increases the risk for depression, only a subset of exposed individuals develop psychiatric illness. The biological mechanisms that protect against depression remain incompletely understood, particularly at the molecular level. Here, we identify a transcriptional network in the nucleus accumbens (NAc), a central brain reward region, that supports stress resilience in both sexes and demonstrate the causal contribution of key hub genes. Using chronic social defeat stress, RNA-seq, and co-expression network analysis, we find sex-specific but overlapping gene modules linked to resilience, anchored by shared hub genes embedded within a common network architecture. Overexpression of these hub genes in stress-naive mice confers stress protection and induces a transcriptional state that is discrete from both susceptible and resilient profiles. These findings position resilience as a structured and targetable molecular phenotype and provide a basis for investigating sex-informed mechanisms of stress adaptation.

neuroscience↗

bioRxiv2025

Transcriptional Profiles in Nucleus Accumbens of Antidepressant Resistance in Chronically Stressed Mice

Treatment-resistant depression (TRD), defined by unsuccessful response to multiple antidepressants, affects approximately one-third of individuals with major depressive disorder, yet its underlying molecular mechanisms remain poorly understood. Here, we developed a preclinical model of TRD in which mice exposed to chronic social defeat stress were sequentially treated with fluoxetine (FLX) and ketamine (KET), allowing behavioral stratification into antidepressant responsive and non-responsive mice. RNA sequencing of the nucleus accumbens (NAc) and prefrontal cortex (PFC) revealed transcriptional signatures associated with treatment outcomes. Prior exposure to FLX exerted a priming effect that facilitated molecular and behavioral responsiveness to KET in a subset of animals in both the NAc and PFC. However, this priming effect was absent in non-responders, despite identical treatment regimes, suggesting a transcriptional divergence underlying differential outcomes. Gene co-expression network analysis identified modules enriched for differentially expressed genes unique to stress-susceptible and FLX-KET nonresponsive mice, as well as modules overlapping with both stress susceptibility and antidepressant resistance. These findings suggest that failed antidepressant treatment can shape the brains molecular landscape in a way that influences subsequent treatment outcomes, and that resistance arises not simply from treatment failure but from an absence of adaptive molecular priming. This work provides insight into the gene networks contributing to antidepressant non-response and highlights a mechanistic framework for modeling TRD in preclinical systems. By identifying molecular correlates of sequential pharmacological resistance, our findings may inform the development of novel therapeutic strategies for individuals with TRD.

neuroscience↗

bioRxiv2024

WTools: a MATLAB-based toolbox for time-frequency analysis

Electroencephalography (EEG) is an established method for investigating neurocognitive functions during human development. In cognitive neuroscience, time-frequency analysis of the EEG is a widely used analytical approach. This paper introduces WTools, a new MATLAB-based toolbox capable of performing time-frequency analysis of EEG signals using complex wavelet transformation. WTools features an intuitive GUI that guides users through the analysis steps, focusing on essential parameters. Being free and open-source, it can be integrated and expanded with new features, making it a handy tool that is growing its popularity in developmental cognitive neuroscience. Here, we provide a detailed description of the WTools algorithm for wavelet transformation and we compare it with state-of-the-art methods implemented in EEGLAB. Alongside the official tool release, we also offer a comprehensive illustrated tutorial to enhance accessibility and promote the transparent and reproducible usage of WTools by the scientific community. HighlightsO_LIWTools is a new MATLAB-based toolbox for time-frequency analysis of the EEG signal C_LIO_LIIt uses wavelet transformation and the algorithm is fully described C_LIO_LIIt is designed to be very user friendly through its simple GUI C_LIO_LIIt is open source and flexible as the code is freely available C_LIO_LIWe provide a step-by-step tutorial and an example dataset to learn the toolbox C_LI

neuroscience↗

bioRxiv2023

Monomethylation of Lysine 27 at Histone 3 Confers Lifelong Susceptibility to Stress

Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling, and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice exposed to early life stress (ELS) or to chronic social defeat stress (CSDS) in adulthood displayed increased enrichment of H3K27me1, and transient decreases in H3K27me2, in the nucleus accumbens (NAc), a key brain-reward region. Stress induction of H3K27me1 was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which is induced by chronic stress and controls H3K27 methylation patterns. Overexpression of the VEFS domain led to social, emotional, and cognitive abnormalities, and altered excitability of NAc D1 mediums spiny neurons. Together, we describe a novel function of H3K27me1 in brain and demonstrate its role as a "chromatin scar" that mediates lifelong stress susceptibility.

neuroscience↗

bioRxiv2023

Transcriptional dissection of symptomatic profiles across the brain of men and women with depression

Major depressive disorder (MDD) is one of the most important causes of disability worldwide. While recent work provides insights into the molecular alterations in the brain of patients with MDD, whether these molecular signatures can be associated with the expression of specific symptom domains in males and females remains unclear. Here, we identified sex-specific gene modules associated with the expression of MDD, combining differential gene expression and co-expression network analyses in six cortical and subcortical brain regions. Our results show varying levels of network homology between males and females across brain regions, although the association between these structures and the expression of MDD remains highly sex-specific. We refined these associations to several symptom domains and identified transcriptional signatures associated with distinct functional pathways, including GABAergic and glutamatergic neurotransmission, metabolic processes, and intracellular signal transduction, across brain regions associated with distinct symptomatic profiles in a sex-specific fashion. In most cases, these associations were specific to males or to females with MDD, although a subset of gene modules associated with common symptomatic features in both sexes was also identified. Together, our findings suggest that the expression of distinct MDD symptom domains is associated with sex-specific transcriptional structures across brain regions.

neuroscience↗

bioRxiv2017

A convergent depression vulnerability pathway encoded by emergent spatiotemporal dynamics

Fluctuations in brain local field potential (LFP) oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these LFP oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors would provide fundamental insights into how the brain signals emotional processes at the network level. Here we use machine learning to integrate LFP activity acquired concurrently from seven cortical and subcortical brain regions into an analytical model that predicts the emergence of depression-related behavioral dysfunction across individual mice subjected to chronic social defeat stress. We uncover a spatiotemporal dynamic network in which activity originates in prefrontal cortex (PFC) and nucleus accumbens (NAc, ventral striatum), relays through amygdala and ventral tegmental area (VTA), and converges in ventral hippocampus (VHip). The activity of this network correlates with acute threat responses and brain-wide cellular firing, and it is enhanced in three independent molecular-, physiological-, and behavioral-based models of depression vulnerability. Finally, we use two antidepressant manipulations to demonstrate that this vulnerability network is biologically distinct from the networks that signal behavioral dysfunction after stress. Thus, corticostriatal to VHip-directed spatiotemporal dynamics organized at the network level are a novel convergent depression vulnerability pathway.

neuroscience↗