Biology subjects

Bhan, A.

Publications and source records attributed to Bhan, A..

3 recordsLinked to original sources

bioRxiv2025

Evening blue light exposure during adolescence induces avoidance behaviors and rewires medial amygdala circuit.

Adolescents are being increasingly exposed to artificial blue light from electronic devices, raising concerns about its effects on brain development and mental health. The medial amygdala (MeA), a brain region critical for emotional regulation, is light-sensitive, yet how evening blue light during puberty influences its circuitry and behavior remains unknown. Using a light cycle disruption paradigm, we found that adolescent mice exposed to evening blue light displayed increased avoidance behaviors compared to those exposed to darkness or reduced blue light conditions. Single-nuclei RNA sequencing revealed altered cell-type composition and disrupted synaptic communication pathways in the MeA. In vivo calcium imaging showed increased activity in MeA somatostatin neurons during avoidance behaviors, while chemogenetic inhibition of these neurons reduced these behaviors. Our findings identify the MeA as a key integrator of emotional responses to environmental blue light, suggesting evening blue light exposure during puberty as a potential risk factor for affective disorders. TeaserEvening blue light exposure during adolescence alters medial amygdala functions, leading to anxiety-like behaviors.

neuroscience↗

bioRxiv2021

Lower Aβ-PET signal in white matter lesions relates to higher extracellular free water in mixed small vessel disease and Alzheimer's pathology

White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (A{beta}-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered A{beta}-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructural alterations, including free water and tissue-specific properties, to A{beta}-PET in WM and to cognition. We included a unique cohort of 115 participants covering the spectrum of low-to-severe white matter hyperintensity (WMH) burden and cognitively normal to dementia. We applied a bi-tensor diffusion-MRI model that differentiates between (i) the extracellular WM compartment (represented via free water), and (ii) the fiber-specific compartment (via free water-adjusted fractional anisotropy [FA]). We observed that, in regions of WMH, a decrease in A{beta}-PET related most closely to higher free water and higher WMH volume. In contrast, in normal-appearing WM, an increase in A{beta}-PET related more closely to higher cortical A{beta} (together with lower free water-adjusted FA). In relation to cognitive impairment, we observed a closer relationship with higher free water than with either free water-adjusted FA or WM PET. Our findings support free water and A{beta}-PET as markers of WM abnormalities in patients with mixed dementia, and contribute to a better understanding of processes giving rise to the WM PET signal.

neuroscience↗

bioRxiv2019

Integrative Genomic Analysis and Functional Studies Reveal GP5, GRN, MPO and MCAM as Causal Protein Biomarkers for Platelet Traits

RationaleMean platelet volume (MPV) and platelet count (PLT) are platelet measures that have been linked to cardiovascular disease (CVD) and mortality risk. Identifying protein biomarkers for these measures may yield insights into CVD mechanisms. ObjectiveWe aimed to identify causal protein biomarkers for MPV and PLT among 71 CVD-related plasma proteins measured in Framingham Heart Study (FHS) participants. Methods and ResultsWe conducted integrative analyses of genetic variants associated with PLT and MPV with protein quantitative trait locus (pQTL) variants associated with plasma proteins followed by Mendelian randomization (MR) to infer causal relations of proteins for PLT/MPV, and tested protein-PLT/MPV association in FHS participants. Utilizing induced pluripotent stem cell (iPSC)-derived megakaryocyte (MK) clones that produce functional platelets, we conducted RNA-sequencing and analyzed transcriptome-wide differences between low- and high-platelet producing clones. We then performed small interfering RNA (siRNA) gene knockdown experiments targeting genes encoding proteins with putatively causal platelet effects in MK clones to examine effects on platelet production. Protein-trait association analyses were conducted for MPV (n = 4,348) and PLT (n = 4,272). Eleven proteins were associated with MPV and 31 with PLT. MR identified four putatively causal proteins for MPV and four for PLT. Glycoprotein V (GP5), granulin (GRN), and melanoma cell adhesion molecule (MCAM) were associated with PLT in both protein-trait and MR analyses. Myeloperoxidase (MPO) showed significant association with MPV in both analyses. MK RNA-sequencing analysis results were directionally concordant with observed and MR-inferred associations for GP5, GRN, and MCAM. In siRNA gene knockdown experiments, silencing GP5, GRN, and MPO decreased platelet counts. ConclusionsBy integrating population genomics data, epidemiological data, and iPSC-derived MK experiments, we identified four proteins that are causally linked to platelet counts. These proteins and genes may be further explored for their utility in increasing platelet production in bioreactors for transfusion medicine purposes as well as their roles in the pathogenesis of CVD via a platelet/blood coagulation-based mechanism.

genomics↗