Chronic leptin administration in developing rats reduces stress responsiveness partly through changes in maternal...

Area of Science:

• Neuroendocrinology
• Developmental Biology
• Hormone Research

Background:

• Leptin's role in adult neuroendocrine function is established, typically inhibiting the hypothalamic-pituitary-adrenal (HPA) axis.
• Neonatal rats exhibit high leptin levels, prompting investigation into leptin's function during early development.
• The influence of leptin on basal and stress-induced HPA activity in neonates remains unclear.

Purpose of the Study:

• To investigate the physiological role of leptin in modulating HPA axis activity in neonatal rats.
• To determine the effects of chronic leptin administration on metabolic parameters and HPA axis function in developing rat pups.
• To explore potential indirect effects of leptin on HPA function via alterations in maternal behavior.

Main Methods:

• Neonatal rat pups were treated daily with vehicle or leptin (1 or 3 mg/kg) from days 2-9 or 6-10 of life.
• Effects on body weight gain, fat pad deposits, and HPA axis activity (CRF mRNA, ACTH, corticosterone) were assessed.
• In situ hybridization was used to measure hypothalamic CRF mRNA levels.
• Plasma hormone concentrations were measured under basal conditions and following ether stress.
• Maternal care behaviors, specifically anogenital licking, were observed.

Main Results:

• Chronic leptin treatment led to dose-dependent reductions in body weight gain and fat pad weight.
• Basal CRF mRNA expression and secretion of ACTH and corticosterone were not significantly altered by leptin.
• Leptin treatment reduced CRF expression post-stress and shortened the ACTH response duration to stress.
• Mothers of leptin-treated pups exhibited increased anogenital licking behavior.
• These findings suggest altered glucocorticoid feedback and potential modulation by maternal behavior.

Conclusions:

• Leptin signaling is functional in neonatal rats, impacting the HPA axis response to stress.
• Leptin can directly influence the HPA axis or indirectly modulate stress responses through maternal behavior.
• Neonatal leptin exposure may alter the developmental trajectory of HPA axis regulation and stress sensitivity.