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Biology subjects

Kim, T. A.

Publications and source records attributed to Kim, T. A..

2 recordsLinked to original sources

Maternal age modulates progeny social behavior via a small RNA-neuropeptide axis

Parental age influences offspring traits across species, yet the molecular pathways by which maternal state modulates progeny neural function remain poorly defined. Here we demonstrate that maternal age in C. elegans regulates progeny avoidance of the social pheromone by modulating the activity of a defined sensory circuit. Progeny of young mothers exhibit stronger activity of the pheromone-sensing ADL neurons and enhanced pheromone avoidance, whereas progeny of old mothers display reduced neuronal responses and weaker repulsion. We identify an ERI-1-microRNA-neuropeptide signaling axis operating in peptidergic AVH interneurons that modulates ADL circuit responsiveness. ERI-1 promotes expression of the neuropeptide gene flp-26 by repressing mir-8207, and signaling from AVH to ADL establishes pheromone sensitivity. Maternal aging is associated with reduced ERI-1 expression in progeny AVH neurons and dampening this signaling pathway. Consequently, progeny of young mothers, though developmentally less robust, disperse more readily from crowded, pheromone-rich environments, offsetting their early-life disadvantages. Our findings reveal a molecular and circuit-level mechanism by which maternal physiology adaptively configures offspring neural computation and behavioral strategy across generations.

neuroscience↗

Characterization of adult hippocampal neurogenesis in the novel AppSAA Knock-in Alzheimer's disease mouse model

Adult hippocampal neurogenesis (AHN) declines with age and is thought to be severely exacerbated in neurodegenerative disorders like Alzheimers disease (AD). Despite numerous efforts to understand how AHN is altered in AD mouse models, results have been inconsistent, largely due to limitations of first-generation transgenic AD mouse models. The newly developed App Knock-in models address many of these limitations. Here, we provide the first in-depth characterization of hippocampal cell populations and AHN across different ages in the novel AppSAAKnock-in (AppKI) mouse model. Our findings reveal that AppKI mice show no early deficits in excitatory dentate granule cells or inhibitory interneurons at 2 and 4 months, but significant loss of both populations emerges by 6 months of age. We also identified a progressive decline in AHN with the survival of newborn neurons being impaired first at 4 months, followed by a deficit in proliferation at 6 months. Furthermore, we demonstrate that exposure to enriched environment, a form of hippocampus-engaged exploration, robustly enhances AHN in AppKI mice, primarily by promoting survival. In conclusion, our study provides a foundational characterization of the AppKI model, establishing a timeline for cellular and AHN deficits.

neuroscience↗