Biology subjects

Benacom, D.

Publications and source records attributed to Benacom, D..

2 recordsLinked to original sources

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↗