Lee, T. Y. | Search bioRxiv

bioRxiv2024

Hypothalamus-specific NSCs derived from hPSCs ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus

The hypothalamus is the brain region that regulates systemic body metabolism and multiple brain functions. The adult hypothalamus harbors neural stem/precursor cell (NSC)-like cells. Along with age-related body changes, the hypothalamic NSC (htNSC) population declines, indicating the potential of htNSC replacement as an anti-aging strategy. Here, we developed protocol to generate htNSCs from human pluripotent stem cells (hPSCs). Implanting the hPSC-derived htNSCs into the hypothalamus of aged mice ameliorated age-related declines in metabolic fitness, physical capacity, and cognitive function. Mechanistically, these anti-aging effects were mediated by inter-tissue communication: enhanced neuronal activity in the htNSC-transplanted hypothalamus stimulated adipose tissues to produce and release the anti-aging molecule eNAMPT into systemic circulation via the sympathetic nervous system. Concurrently, the aged inflammatory environment in the hypothalamus was alleviated by peripheral anti-aging signals. Collectively, our findings support the potential of anti- or healthy aging therapies by targeting hypothalamus.

cell biology↗

bioRxiv2022

The neuropeptide FLP-17 regulates an oviposition behavior in the nematode Caenorhabditis elegans that increases maternal reproductive fitness in low oxygen environments

SUMMARYThe ability for animals to adapt their behaviors to specific environments is imperative to increase their evolutionary success. This is particularly true for behaviors such as parental behaviors that directly affect reproductive fitness. Here, we identified an oviposition behavior in the nematode C. elegans that increases the survival of the young. In standard laboratory culture, the bacterivorous hermaphrodite mothers lay eggs across a 2D E. coli lawn with no discernable pattern. However, in 3D culture they display a stereotypical behavior in which they temporarily leave the bacteria to lay eggs far away from the E. coli colony, resulting in a scattered ring of eggs located outside the bacteria. This oviposition behavior requires low oxygen levels and is regulated by the neuropeptide FLP-17 and its cognate receptor EGL-6. We confirm that a circuitry involving the oxygen-sensing BAG neurons and the vulva muscle-controlling HSN motor neurons regulates oviposition behavior. We show that loss of proper oviposition behavior results in lower reproductive fitness for the mothers and embryonic lethality for the eggs laid in bacteria under hypoxic conditions. Finally, we show that the degree of oviposition behavior varies among wild strains of C. elegans found in nature. The ability for C. elegans mothers to sense their environments and adjust their behaviors in adverse conditions is likely an adaptation that has allowed the worm to thrive in diverse and often hazardous habitats.

neuroscience↗