Biology subjects

Yu, T.-S.

Publications and source records attributed to Yu, T.-S..

3 recordsLinked to original sources

bioRxiv2023

Traumatic brain injury-induced fear generalization in mice involves hippocampal memory trace dysfunction and is alleviated by (R,S)-ketamine

INTRODUCTIONTraumatic brain injury (TBI) is a debilitating neurological disorder caused by an impact to the head by an outside force. TBI results in persistent cognitive impairments, including fear generalization, the inability to distinguish between aversive and neutral stimuli. The mechanisms underlying fear generalization have not been fully elucidated, and there are no targeted therapeutics to alleviate this symptom of TBI. METHODSTo identify the neural ensembles mediating fear generalization, we utilized the ArcCreERT2 x enhanced yellow fluorescent protein (EYFP) mice, which allow for activity-dependent labeling and quantification of memory traces. Mice were administered a sham surgery or the controlled cortical impact (CCI) model of TBI. Mice were then administered a contextual fear discrimination (CFD) paradigm and memory traces were quantified in numerous brain regions. In a separate group of mice, we tested if (R,S)-ketamine could decrease fear generalization and alter the corresponding memory traces in TBI mice. RESULTSTBI mice exhibited increased fear generalization when compared with sham mice. This behavioral phenotype was paralleled by altered memory traces in the DG, CA3, and amygdala, but not by alterations in inflammation or sleep. In TBI mice, (R,S)-ketamine facilitated fear discrimination and this behavioral improvement was reflected in DG memory trace activity. CONCLUSIONSThese data show that TBI induces fear generalization by altering fear memory traces, and that this deficit can be improved with a single injection of (R,S)-ketamine. This work enhances our understanding of the neural basis of TBI-induced fear generalization and reveals potential therapeutic avenues for alleviating this symptom.

animal behavior and cognition↗

bioRxiv2021

Astrocyte-derived ApoE is Required for the Maturation of Injury-induced Hippocampal Neurons and Regulates Cognitive Recovery After Traumatic Brain Injury

Polymorphisms in the apolipoprotein E (ApoE) gene confer a major genetic risk for the development of late-onset Alzheimers disease (AD) and are predictive of outcome following traumatic brain injury (TBI). Alterations in adult hippocampal neurogenesis have long been associated with both the development of AD and recovery following TBI, and ApoE is known to play a role in this process. In order to determine how ApoE might influence hippocampal injury-induced neurogenesis, we developed a novel conditional system whereby functional ApoE from astrocytes was ablated just prior to injury. While successfully ablating 90% of astrocytic ApoE just prior to a closed cortical impact injury in mice, we observed an attenuation in the development of newly born neurons using a GFP-expressing retrovirus, but not in existing hippocampal neurons visualized with a Golgi stain. Intriguingly, animals with a "double-hit", i.e. injury and ApoE conditionally inactivated in astrocytes, demonstrated the most pronounced impairments in the hippocampal-dependent Morris water maze test, failing to exhibit spatial memory after both acquisition and reversal training trials. In comparison, conditional knockout mice without injury displayed impairments but only in the reversal phase of the test, suggesting accumulative effects of astrocytic ApoE deficiency and traumatic brain injury on AD-like phenotypes. Together, these findings demonstrate that astrocytic ApoE is required for functional injury-induced neurogenesis following traumatic brain injury. Significance StatementApoE has long been implicated in the development of Alzheimers disease and recovery from traumatic brain injury via unknown mechanisms. Using a novel conditional ablation model of mouse ApoE and subsequent tracing of individual hippocampal neurons, we demonstrate its requirement in injury-induced neurogenesis for proper dendritic arborization and cognitive function in hippocampal-dependent learning and memory tasks.

neuroscience↗

bioRxiv2020

The movement of a leaf-derived mobile AGL24 mRNA specifies floral organ identity in Arabidopsis

Cell-to-cell and inter-organ communication play pivotal roles in synchronizing and coordinating plant development. In addition to serving as templates for protein translation within cells, many mRNAs can move and exert their function non-cell-autonomously. However, because the proteins encoded by some mobile mRNAs are also mobile, whether the systemic function of mobile mRNAs is attributed to proteins transported distally or translated locally remains controversial. Here, we show that Arabidopsis AGAMOUS-LIKE 24 (AGL24) mRNA acts as a leaf-derived signal to specify meristem identity. AGL24 is expressed in both apex and leaves. Upon floral meristem (FM) transition, apex-expressed AGL24 is transcriptionally inhibited by APETALA1 (AP1) to ensure FM differentiation. The leaf-expressed AGL24 can act as a mobile signal to bypass AP1 inhibition and revert FM differentiation. Although AGL24 mRNA is expressed in leaves, AGL24 protein is rapidly degraded in leaves. In contrast, AGL24 mRNA can move long distance from leaf to apex where the translocated AGL24 mRNAs can be used as templates to translate into proteins. Thus, the movement of AGL24 mRNA can provide the developmental plasticity to fit with environmental dynamics.

plant biology↗