PDF(Pubmed)
Abstract：
Precise control of neuronal activity is crucial for the proper functioning of neurons. How lipid homeostasis contributes to neuronal activity and how much of it is regulated by cells autonomously is unclear. In this study, we discovered that absence of the lipid regulator nhr-49, a functional ortholog of the peroxisome proliferator-activated receptor (PPAR) in Caenorhabditis elegans, resulted in defective pathogen avoidance behavior against Pseudomonas aeruginosa (PA14). Functional NHR-49 was required in the neurons, and more specifically, in a set of oxygen-sensing body cavity neurons, URX, AQR, and PQR. We found that lowering the neuronal activity of the body cavity neurons improved avoidance in nhr-49 mutants. Calcium imaging in URX neurons showed that nhr-49 mutants displayed longer-lasting calcium transients in response to an O2 upshift, suggesting that excess neuronal activity leads to avoidance defects. Cell-specific rescue of NHR-49 in the body cavity neurons was sufficient to improve pathogen avoidance, as well as URX neuron calcium kinetics. Supplementation with oleic acid also improved avoidance behavior and URX calcium kinetics, suggesting that the defective calcium response in the neuron is due to lipid dysfunction. These findings highlight the role of cell-autonomous lipid regulation in neuronal physiology and immune behavior.
摘要：
神经元活动的精确控制对于神经元的正常运作至关重要。目前尚不清楚脂质稳态如何促进神经元活动以及其中有多少受细胞自主调节。在这项研究中,我们发现缺乏脂质调节剂nhr-49，这是秀丽隐杆线虫中过氧化物酶体增殖物激活受体（PPAR）的功能性直系同源物，导致针对铜绿假单胞菌（PA14）的病原体回避行为缺陷。神经元需要功能性NHR-49，更具体地说，在一组氧感应体腔神经元中，URX,AQR,和PQR。我们发现，降低体腔神经元的神经元活性可改善nhr-49突变体的回避。URX神经元的钙成像显示，nhr-49突变体在响应O2升高时表现出更持久的钙瞬变，这表明过度的神经元活动会导致回避缺陷。在体腔神经元中NHR-49的细胞特异性拯救足以改善病原体的回避，以及URX神经元钙动力学。补充油酸也改善了回避行为和URX钙动力学，提示神经元中的钙反应缺陷是由于脂质功能障碍。这些发现强调了细胞自主脂质调节在神经元生理和免疫行为中的作用。
