Resveratrol alleviates hippocampal oxidative stress, neuroinflammation and pyroptosis and reduces anxiety-like behavior in broilers under cold exposure.

Abstract

Resveratrol (Res) exhibits antioxidant properties and neuroprotection. To investigate its protective effect, 576 one-day-old broilers were assigned to eight groups, reared under normal temperature or cold exposure (CE) and received the basal diet with 0, 250, 500, and 750 mg/kg Res, respectively. Broilers underwent behavioral tests, and hippocampus were collected. The results showed that after CE, the latency to first move and vocalise in open field test, induction times in tonic immobility test, and the latency to move, eat and vocalise in attention bias test were increased, while the numbers of movement steps and total vocalizations in attention bias test were decreased. Hematoxylin-eosin and Nissl staining displayed the perivascular aggregation of inflammatory cells and necrosis, disordered and sparse neurons, and reduced number of neurons in CE-broiler hippocampus. Transmission electron microscopy showed that CE caused synaptic terminals swelling and reduced the number of synaptic vesicles. Res restored abnormal changes in behaviors, histopathology and microstructure. CE decreased the CAT, T-SOD, GSH-px, and T-AOC activities, increased the H₂O₂ and MDA levels, upregulated the expression of genes and proteins related to inflammation (NF-κBp65, TNF-α, IL-2, IL-6, IL-8, IL-17) and pyroptosis (NLRP3, Caspase-1, GSDMD, ASC, IL-1β, IL-18), and depressed the expression of SIRT1 and BDNF/TrκB (CREB, FRS2, CRF, BRAF, PI3K) mRNA and proteins. Res normalized the abnormal expression in CE-broiler hippocampus. Overall, 500 mg/kg Res, an optimal supplementation dosage, relieved oxidative and inflammatory injuries by enhancing antioxidative capacity and inhibiting NF-κB signaling and NLRP3 inflammasome, alleviating anxiety-like behaviors in CE-broilers via modulating the SIRT1/BDNF/TrκB signaling.