Biology subjects

Benacom, D.

Publications and source records attributed to Benacom, D..

4 recordsLinked to original sources

bioRxiv2026

Short-term, Long-term, and Genetic Determinants of Human Plasma Proteome Variability

Plasma proteomics is increasingly used for biomarker discovery and predictive modeling, yet diurnal protein trajectories remain insufficiently characterized. In our review of recent proteomic biomarker studies, 43% of the identified biomarkers had previously been reported to display 24-h rhythmicity. We demonstrate that ignoring these short-term dynamic effects compromises the robustness of reported models predicting health outcomes. We integrated a population-scale multi-ethnic longitudinal cohort with repeated measures over 10 years, with two cohorts of healthy adults undergoing frequent plasma sampling across days under controlled circadian, sleep and food-intake conditions. This design enabled estimation of short-term intraindividual variability (ST), long-term intraindividual variability (LT), population-level variability (POP) and genetic effects (GEN) across 7,289 protein targets. ST, LT, POP, and GEN define diverse protein trajectories, including rapid dynamics, long-term change, and individual-specific signatures. Using and generalizing this framework will facilitate covariate selection, study design, biomarker prioritization, and variability-aware modeling by users of proteomic data.

genomics↗

bioRxiv2024

Motor cortex perineuronal net modulation improves motor function in a Parkinson's disease mouse model

The 6-OHDA mouse model recapitulates midbrain dopaminergic cell loss and associated motor deficits akin to those observed in Parkinsons disease. Emerging evidence suggests that modulating interneurons in the primary motor cortex could offer a means to mitigate symptoms. In the cortex, perineuronal nets (PNNs), a specialized extracellular matrix structure generally present around fast-spiking parvalbumin interneurons, can modulate neural activity and circuit plasticity. We found that removing PNNs through unilateral or bilateral ChABC injection in the motor cortex temporarily altered motor behavior. Surprisingly, bilateral reduced motor cortex PNNs are observed two weeks after unilateral 6-OHDA midbrain lesions, whereas five weeks after lesion, PNNs return to control levels. Subsequent bilateral ChABC injections significantly improved motor function in 6-OHDA animals only when associated with motor stimulation involving enriched housing and daily motor training. Thus, PNN modulation in the motor cortex of a Parkinsons disease model enables local circuits to adapt to the loss of dopaminergic inputs, resulting in improved motor behavior.

neuroscience↗

bioRxiv2023

Plasticity state-dependent changes in visual cortex parvalbumin interneuron mRNA translation and chromatin

The juvenile brain is shaped by critical periods (CPs) of plasticity regulated in part by parvalbumin (PV) interneurons. The "reopening" of CPs has been explored in brain disorders, yet it remains unclear whether adult enhanced plasticity recapitulates developmental mechanisms. We profiled visual cortex PV-specific ribosome-associated mRNAs at the CP peak and in two adult plasticity paradigms, chondroitinase ABC (ChABC) injection and extracellular OTX2 blockade. No shared translatomic signature emerged between the three conditions. Nonetheless, CP and ChABC-induced plasticity shared genes coding for synaptic components and extracellular matrix. Condition-specific pathways highlighted mechano-transduction and cytoskeletal remodeling for ChABC plasticity and DNA repair and heterochromatin for CP plasticity. These juvenile pathways were supported by elevated {gamma}H2AX, H3K9me3, and DAPI foci in PV cells uniquely during the CP. Thus, adult plasticity does not simply reinstate juvenile mechanisms, but instead may recruit partially overlapping, condition-specific molecular pathways revealing candidate targets for enhancing adult plasticity.

neuroscience↗

bioRxiv2021

OTX2 homeoprotein functions in adult choroid plexus

Choroid plexus secretes cerebrospinal fluid important for brain development and homeostasis. The OTX2 homeoprotein is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative roles for OTX2 in choroid plexus function, including cell signaling and adhesion, and show that it regulates the expression of factors secreted into cerebrospinal fluid, notably transthyretin. We show that Otx2 expression impacts choroid plexus immune and stress responses, and also affects splicing which leads to changes in mRNA isoforms of proteins implicated in oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell autonomous target regions such as visual cortex and ventricular-subventricular zone, we identified putative targets involved in cell adhesion, chromatin structure and RNA processing. Thus, OTX2 retains important roles in choroid plexus function and brain homeostasis throughout life.

neuroscience↗