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Biology subjects

Lau, A. G.

Publications and source records attributed to Lau, A. G..

2 recordsLinked to original sources

Persistent Cognitive Impairment and Bone Health Following Helium (4He) Ion Exposure: Implications for Space Travel

The current study investigated the long-term neurobehavioral and physiological effects of low-dose helium (4He; 250 MeV/n) ion exposure, a significant component of galactic cosmic radiation (GCR), on male Long Evans rats. Groups of rats were trained on the rodent psychomotor vigilance test (rPVT) and irradiated at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Following exposure, they were tested in the rPVT from 30 - 180 days, and assessed for social recognition memory at 30, 90, and 180 days. At each time point, blood and bone samples were collected for subsequent analysis. We found that acute exposure to 4He ions (25 cGy) significantly impaired sustained attention, resulting in increased lapses in attention, increased reaction time measures, and decreased correct responses. However, exposure to 5 cGy 4He ions only increased some reaction time measures in the rPVT. Both groups displayed impaired social recognition memory. When deficits were found, they persisted for 180 days post-exposure, showing no signs of recovery. Notably, impairments in sustained attention appeared to worsen over time. While these low exposure doses of 4He did not significantly alter overall bone mechanical properties, specific individual parameters of bone strength were affected, and age-related changes likely played a role in observed skeletal integrity changes. Furthermore, we identified significant correlations between circulating cytokines (TNF-, IL-1{beta}), undercarboxylated osteocalcin (ucOC) levels, and bone biomechanical properties with behavioral performances. These findings suggest the potential for these blood- and bone-based targets to serve as diagnostic biomarkers for radiation-induced neurobehavioral effects, opening avenues for future countermeasure development. The sustained and progressive nature of the neurobehavioral deficits observed underscores the critical need for effective countermeasures to protect astronaut health and performance during exploration-class missions.

animal behavior and cognition↗

Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity

Homeostatic synaptic plasticity is a non-Hebbian synaptic mechanism that adjusts synaptic strength to maintain network stability while achieving optimal information processing. Among the molecular mediators shown to regulate this form of plasticity, synaptic signaling through retinoic acid (RA) and its receptor, RAR, has been shown to be critically involved in the homeostatic adjustment of synaptic transmission in both hippocampus and sensory cortices. In this study, we explore the molecular mechanism through which postsynaptic RA and RAR regulates presynaptic neurotransmitter release during prolonged synaptic inactivity at excitatory synapses. We show that RAR binds to a subset of dendritically sorted brain-derived neurotrophic factor (BDNF) mRNA splice isoforms and represses their translation. The RA-mediated translational de-repression of postsynaptic BDNF results in the retrograde activation of presynaptic Tropomyosin receptor kinase B (TrkB) receptors, facilitating presynaptic homeostatic compensation through enhanced presynaptic release. Together, our study illustrates a RA-mediated retrograde synaptic signaling pathway through which postsynaptic protein synthesis during synaptic inactivity drives compensatory changes at presynaptic site.

neuroscience↗