Acute thermal stress severely disrupts the systemic coordination essential for thermal homeostasis in bivalves, yet the underlying neuro-peripheral regulatory mechanisms remain poorly resolved. In the present study, the temporal coordination of neural and peripheral responses to acute heat stress in the Yesso scallop ( Mizuhopecten yessoensis ) was systematically investigated leveraging time-resolved transcriptomics, co-expression network analysis, and in vivo functional validation. Transcriptomic profiling demonstrated that the neural ganglion mounts a rapid and robust transcriptional response within 15–30 min, significantly preceding the downstream activation of antioxidant defenses in the adductor muscle at 60 min. This distinct temporal divergence is indicative of a highly coordinated neuro-peripheral axis. Subsequent weighted gene co-expression network analysis (WGCNA) identified a critical early-response module enriched in transmembrane transport mechanisms, pinpointing two solute carrier transporters ( SLC6A5 and SLC17A5 ) as the regulatory hub genes. These specific transporters likely act antagonistically to orchestrate an excitatory/inhibitory (E/I) balance, which is crucial for maintaining central neural homeostasis and ensuring accurate signal propagation to peripheral tissues. In vivo RNA interference (RNAi) targeting either transporter impaired systemic antioxidant mobilization and exacerbated cellular apoptosis, confirming their indispensable roles in mitigating systemic stress injury. Notably, exogenous glycine supplementation fortified thermal resilience by stabilizing inhibitory transport mechanisms, thereby prolonging the effective physiological intervention window and significantly reducing apoptotic lesions in both ganglion and muscle tissues. Together, these findings elucidate a temporally coordinated neuro-peripheral regulatory framework for thermal adaptation in marine bivalves. Furthermore, we underscore SLC-mediated neurotransmitter balance as a promising molecular target, suggesting that targeted amino acid supplementation represents a viable, functional nutritional strategy to mitigate mass summer mortalities in commercial scallop aquaculture under escalating climate change scenarios.
Qiao et al. (Fri,) studied this question.