Biology subjects

Zheng, J. Q.

Publications and source records attributed to Zheng, J. Q..

4 recordsLinked to original sources

bioRxiv2024

Sexual Dimorphism in Age-Dependent Neurodegeneration After Mild Head Trauma in Drosophila: Unveiling the Adverse Impact of Female Reproduction

Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration. However, it remains challenging to establish a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegenerative deficits, nor do we know how sex and age compound the outcome. Using a Drosophila model, we demonstrate that exposure to mild head trauma causes neurodegenerative conditions that emerge late in life and disproportionately affect females. Increasing age-at-injury further exacerbates this effect in a sexually dimorphic manner. We further identify Sex Peptide (SP) signaling as a key factor in female susceptibility to post-injury brain deficits. RNA sequencing highlights a reduction in innate immune defense transcripts specifically in mated females during late life. Our findings establish a causal relationship between early head trauma and late-life neurodegeneration, emphasizing sex differences in injury response and the impact of age-at-injury. Finally, our findings reveal that reproductive signaling adversely impacts female response to mild head insults and elevates vulnerability to late-life neurodegeneration.

neuroscience↗

bioRxiv2023

A novel enhancer-AAV approach selectively targeting dentate granule cells

The mammalian brain contains the most diverse array of cell types of any organ, including dozens of neuronal subtypes with distinct anatomical and functional characteristics. The brain leverages these neuron-type-specializations to perform diverse circuit operations and thus execute different behaviors properly. Through the use of Cre lines, access to specific neuron types has steadily improved over past decades. Despite their extraordinary utility, development and cross-breeding of Cre lines is time-consuming and expensive, presenting a significant barrier to entry for many investigators. Furthermore, cell-based therapeutics developed in Cre mice are not clinically translatable. Recently, several AAV vectors utilizing neuron-type-specific regulatory transcriptional sequences (enhancer-AAVs) were developed which overcome these limitations. Using a publicly available RNAseq dataset, we evaluated the potential of several candidate enhancers for neuron-type-specific targeting in the hippocampus. Here we identified a promising enhancer-AAV for targeting dentate granule cells and validated its selectivity in wild-type adult mice.

neuroscience↗

bioRxiv2022

Characterizing the role of Ca2+ fluxes in defining fast and slow components of spontaneous Ca2+ local transients in OPCs using computational modeling

1Spontaneous Ca2+ local transients (SCaLTs) in isolated oligodendrocyte precursor cells (OPCs) are largely regulated by the following fluxes: store-operated Ca2+ entry (SOCE), Na+/Ca2+ exchange (NCX), Ca2+ pumping through Ca2+-ATPases, and Ca2+-induced Ca2+-release through Ryanodine receptors (RyR) and inositoltriphosphate receptors (IP3R). However, the relative contributions of these fluxes in mediating fast spiking and slow baseline oscillations seen in SCaLTs remain incompletely understood. Here, we developed a stochastic spatiotemporal computational model to simulate SCaLTs in a homogeneous medium with ion flow between the extracellular, cytoplasmic and endoplasmic-reticulum compartments. By simulating the model and plotting both the histograms of SCaLTs obtained experimentally and from the model as well as the standard deviation of interspike intervals (ISI) against ISI averages of multiple model and experimental realizations we revealed that: SCaLTs exhibit very similar characteristics between the two datasets, they are mostly random, they encode information in their frequency, and the slow baseline oscillations could be due to the stochastic slow clustering of IP3R (modeled as an Ornstein-Uhlenbeck noise process). Bifurcation analysis of a deterministic temporal version of the model shows that the contribution of fluxes to SCaLTs depends on the parameter regime and that the combination of excitability, stochasticity, and mixed-mode oscillations are responsible for irregular spiking and doublets in SCaLTs. Additionally, our results demonstrate that blocking each flux reduces SCaLTs frequency and that the reverse (forward) mode of NCX decreases (increases) SCaLTs. Taken together, these results provide a quantitative framework for SCaLT formation in OPCs.

neuroscience↗

bioRxiv2021

Repetitive Mild Head Trauma Induces Activity-Mediated Lifelong Brain Deficits in a Novel Drosophila Model

Mild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Here, we developed a novel head impact system to investigate the long-term effects of mild head trauma on brain structure and function, as well as the underlying mechanisms in Drosophila melanogaster. We find that Drosophila subjected to repetitive head impacts develop long-term deficits, including impaired startle-induced climbing, progressive brain degeneration, and shortened lifespan, all of which are substantially exacerbated in female flies. Interestingly, head impacts elicit an elevation in neuronal activity and its acute suppression abrogates the detrimental effects in female flies. Together, our findings validate Drosophila as a suitable model system for investigating the long-term effects of mild head trauma, suggest an increased vulnerability in brain injury in female flies, and indicate that early altered neuronal excitability may be a key mechanism linking mild brain trauma to chronic degeneration.

neuroscience↗