TY - JOUR

T1 - Effects of chronic silencing of relaxin-3 production in nucleus incertus neurons on food intake, body weight, anxiety-like behaviour and limbic brain activity in female rats

AU - de Avila, Camila

AU - Chometton, Sandrine

AU - Ma, Sherie

AU - Pedersen, Lola Torz

AU - Timofeeva, Elena

AU - Cifani, Carlo

AU - Gundlach, Andrew L.

PY - 2020

Y1 - 2020

N2 - Eating disorders are frequently triggered by stress and are more prevalent in women than men. First signs o similar to ften appear during early adolescence, but the biological basis for the sex-specific differences is unknown. Central administration of native relaxin-3 (RLN3) peptide or chimeric/truncated analogues produces differential effects on food intake and HPA axis activity in adult male and female rats, but the precise role of endogenous RLN3 signalling in metabolic and neuroendocrine control is unclear. Therefore, we examined the effects of microRNA-induced depletion (knock-down) of RLN3 mRNA/(peptide) production in neurons of the brainstem nucleus incertus (NI) in female rats on a range of physiological, behavioural and neurochemical indices, including food intake, body weight, anxiety, plasma corticosterone, mRNA levels of key neuropeptides in the paraventricular nucleus of hypothalamus (PVN) and limbic neural activity patterns (reflected by c-fos mRNA). Validated depletion of RLN3 in NI neurons of female rats (n = 8) produced a small, sustained (similar to 2%) decrease in body weight, an imbalance in food intake and an increase in anxiety-like behaviour in the large open field, but not in the elevated plus-maze or light/dark box. Furthermore, NI RLN3 depletion disrupted corticosterone regulation, increased oxytocin and arginine-vasopressin, but not corticotropin-releasing factor, mRNA, in PVN, and decreased basal levels of c-fos mRNA in parvocellular and magnocellular PVN, bed nucleus of stria terminalis and the lateral hypothalamic area, brain regions involved in stress and feeding. These findings support a role for NI RLN3 neurons in fine-tuning stress and neuroendocrine responses and food intake regulation in female rats.

AB - Eating disorders are frequently triggered by stress and are more prevalent in women than men. First signs o similar to ften appear during early adolescence, but the biological basis for the sex-specific differences is unknown. Central administration of native relaxin-3 (RLN3) peptide or chimeric/truncated analogues produces differential effects on food intake and HPA axis activity in adult male and female rats, but the precise role of endogenous RLN3 signalling in metabolic and neuroendocrine control is unclear. Therefore, we examined the effects of microRNA-induced depletion (knock-down) of RLN3 mRNA/(peptide) production in neurons of the brainstem nucleus incertus (NI) in female rats on a range of physiological, behavioural and neurochemical indices, including food intake, body weight, anxiety, plasma corticosterone, mRNA levels of key neuropeptides in the paraventricular nucleus of hypothalamus (PVN) and limbic neural activity patterns (reflected by c-fos mRNA). Validated depletion of RLN3 in NI neurons of female rats (n = 8) produced a small, sustained (similar to 2%) decrease in body weight, an imbalance in food intake and an increase in anxiety-like behaviour in the large open field, but not in the elevated plus-maze or light/dark box. Furthermore, NI RLN3 depletion disrupted corticosterone regulation, increased oxytocin and arginine-vasopressin, but not corticotropin-releasing factor, mRNA, in PVN, and decreased basal levels of c-fos mRNA in parvocellular and magnocellular PVN, bed nucleus of stria terminalis and the lateral hypothalamic area, brain regions involved in stress and feeding. These findings support a role for NI RLN3 neurons in fine-tuning stress and neuroendocrine responses and food intake regulation in female rats.

KW - Anxiety

KW - Feeding

KW - Female rats

KW - Nucleus incertus

KW - Relaxin-3

KW - Stress

KW - CORTICOTROPIN-RELEASING-FACTOR

KW - PITUITARY-ADRENAL AXIS

KW - NERVOUS-SYSTEM CONTROL

KW - RECEPTOR RXFP3

KW - MESSENGER-RNA

KW - BED NUCLEUS

KW - STRIA TERMINALIS

KW - BINDING-SITES

KW - STRESS

KW - PEPTIDE

U2 - 10.1007/s00213-019-05439-1

DO - 10.1007/s00213-019-05439-1

M3 - Journal article

C2 - 31897576

VL - 237

SP - 1091

EP - 1106

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 4

ER -