Biology subjects

Li, J.-y.

Publications and source records attributed to Li, J.-y..

3 recordsLinked to original sources

bioRxiv2025

KiF1a-regulated neuronal infrastructures in sensory and prefrontal cortices essential for fear memory and anxiety

Stress in social activities induces fears. Cellular infrastructures and molecular profiles underlying fear-relevant psychosis remain elusive. By giving psychological stress to mice that watched fear scenes in the resident/intruder paradigm, we have studied the features of neuronal infrastructures in visual, auditory and medial prefrontal cortices correlated to fear-induced anxiety by approaches of behavior task, neural tracing, molecular biology and electrophysiology in vivo. This psychological stress causes observational mice fears specific to resident mouse and anxiety. This social phobia is associated with the interconnections newly emerged among visual, auditory and medial prefrontal cortices as well as among intramodal neurons. These cortical neurons receive the new synapse innervations from their interconnected neurons alongside the innate synapse innervations, and become to encode the stress signals including battle image and battle sound. The KiF1a knockdown in the medial prefrontal cortex precludes the formations of neuronal infrastructures and social phobia. KiF1a-mediated intracellular transportation in the medial prefrontal cortex is essential for the recruitment of associative memory neurons that encode fear scenes and anxiety. HighlightO_LIPsychological stress induces fears and interconnections among sensory and prefrontal cortices. C_LIO_LIAssociative memory neurons in these cortices are recruited to encode fear scenes and anxiety. C_LIO_LIKiF1a-mediated transportation essential for these cellular infrastructures relevant to learned fear. C_LI

neuroscience↗

bioRxiv2023

High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen

High-altitude polycythemia (HAPC) is a chronic condition prevalent in individuals residing at high altitudes (HA), characterized by an augmented production of red blood cells (RBCs) due to hypoxic conditions. Despite its prevalence, the pathophysiological basis and molecular mechanisms driving HAPC remain largely unelucidated. In our study, we utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings revealed that HH exposure significantly stimulates erythropoiesis, leading to erythrocytosis. This was accompanied by a notable sequence of splenic changes, initially characterized by splenic contraction, which subsequently progressed to splenomegaly over 14 days. A key observation was the impairment on the capacity of spleen to process RBCs, primarily attributed to a reduction in splenic macrophages located in the red pulp. Extended HH treatment over 7 and 14 days precipitated increased iron mobilization and the onset of ferroptosis within the spleen. This was evidenced by altered expression levels of iron metabolism and ferroptosis-related proteins, paralleling gene expression patterns observed in human peripheral blood mononuclear cells. Single-cell sequencing of splenic tissue post-HH exposure demonstrated a marked decrease in macrophage populations after 7 days. Our study further disclosed a significant increase in RBCs retention in the spleen following HH exposure, likely a consequence of diminished red pulp macrophages (RPMs) and erythrophagocytosis. This hypothesis was corroborated through comprehensive analyses involving flow cytometry, histological staining, and immunostaining, which collectively provided a detailed understanding of RBCs dynamics under HH conditions. In vitro analyses substantiated the decline in primary splenic macrophages and induction of ferroptosis under hypoxic treatment, effects that were relieved by pre-treatment with the ferroptosis inhibitor ferrostatin-1. Collectively, our data suggest that HH exposure initiates splenic ferroptosis, leading primarily to a decrease in RPMs. This decrease potentially impacts erythrophagocytosis, contributing to increased RBCs retention and subsequent splenomegaly. Such changes could potentially foster continuous RBCs production and accelerate the progress of HAPC. In conclusion, our study highlights the important role of the spleen and splenic macrophages in the pathogenesis of HAPC, providing crucial insights into the disease progression and potential therapeutic targets.

physiology↗

bioRxiv2018

The making of a Lewy body: the role of alpha-synuclein post-fibrillization modifications in regulating the formation and the maturation of pathological inclusions.

Although converging evidence point to alpha-synuclein (a-syn) aggregation and Lewy body (LB) formation as central events in Parkinson's disease (PD), the molecular mechanisms that regulate these processes and their role in disease pathogenesis remain poorly understood. Herein, we applied an integrative biochemical, structural and imaging approach to elucidate the sequence, molecular and cellular mechanisms that regulate LB formation in primary neurons. Our results establish that post-fibrillization C-terminal truncation mediated by calpains 1 and 2 and potentially other enzymes, plays critical roles in regulating a-syn seeding, fibrillization and orchestrates many of the events associated with LB formation and maturation. These findings combined with the abundance of a-syn truncated species in LBs and pathological a-syn aggregates have significant implications for ongoing efforts to develop therapeutic strategies based on targeting the C-terminus of a-syn or proteolytic processing of this region.

neuroscience↗