Central Neuropeptide Y Plays an Important Role in Mediating the Adaptation Mechanism Against Chronic Stress in Male Rats

Abstract

Exposure to continuous life stress often causes gastrointestinal (GI) symptoms. Studies have shown that neuropeptide Y (NPY) counteracts the biological actions of corticotrophin-releasing factor (CRF) and is involved in the termination of the stress response. However, in chronic repeated restraint stress (CRS) conditions, the actions of NPY on GI motility remain controversial. To evaluate the role of NPY in mediation of the adaptation mechanism and GI motility in CRS conditions, a CRS rat model was set up. Central CRF and NPY expression levels were analyzed, serum corticosterone and NPY concentrations were measured, and GI motor function was evaluated. The NPY Y1 receptor antagonist BIBP-3226 was centrally administered before stress loading, and on days 1 through 5 of repeated stress, the central CRF and the serum corticosterone concentrations were measured. In addition, gastric and colonic motor functions were evaluated. The elevated central CRF expression and corticosterone concentration caused by acute stress began to fall after 3 days of stress loading, whereas central NPY expression and serum NPY began to increase. GI dysmotility also returned to a normal level. Pretreatment with BIBP-3226 abolished the adaptation mechanism and significantly increased CRF expression and the corticosterone concentration, which resulted in delayed gastric emptying and accelerated fecal pellet output. Inhibited gastric motility and enhanced distal colonic motility were also recorded. CRS-produced adaptation, overexpressed central CRF, and GI dysmotility observed in acute restraint stress were restored to normal levels. Central NPY via the Y1 receptor plays an important role in mediating the adaptation mechanism against chronic stress.

Intranasal Administration of Oxytocin Attenuates Stress Responses Following Chronic Complicated Stress in Rats

“…All procedures were carried out according to the manufacturer's instructions, as previously reported. 24,25 Quantitative Real-time Polymerase Chain Reaction…”

“…Punches were collected from the left and right PVN (1.8 mm caudal to bregma; 0.4 mm lateral to midline; 7.6 mm ventral to the brain surface), as previously reported. 8,24 All coordinates were based on the rat brain atlas and hypothalamic images of previously reported. 26 Samples were stored at -80℃ until use.…”

“…For an internal control, the following were designed to amplify rat β-actin: sense primer 5'-TGGCACCACACCTTCTACAATGAG-3', antisense primer 5'-GGGTCATCTTTTCACGGTTGG-3', as previously reported. 8,24 Quantitative polymerase chain reaction (PCR) was performed by using SYBR Premix Ex Taq (TaKaRa Biotech, Dalian, China). Amplification reactions were performed using ABI 7500 Real-time PCR instrument (Applied Biosystems, San Mateo, CA, USA).…”

“…The relative amount of each mRNA was normalized by the amount of β-actin mRNA, as previously reported. 8,24 Measurement of Solid Gastric Emptying Rats were fasted for 24 hours prior to the measurement of GE. Preweighed standard rodent pellets (1.6 g) were given, the rats that did not consume 1.6 g of food within 10 minutes were excluded from the study.…”

Neuropeptide Y Gene × Environment Interaction Predicts Resilience and Positive Future Focus

“…In previous studies, it has been proven that the NPY gene can adapt the internal mechanism against chronic stress, and also resists the biological actions of the corticotrophin‐releasing factor (CRF) and inhibits negative reactions to stress (Yang et al., ). The C allele of NPY rs16147 competes with other allelic variants of the promoter haplotypes, resulting in a 30 per cent decrease in basal expression.…”