Developmental changes in the hypothalamic mRNA expression levels of brain‐derived neurotrophic factor and serum leptin levels: Their responses to fasting in male and female rats

Abstract

The actions and responses of hypothalamic appetite regulatory factors change markedly during the neonatal to pre-pubertal period in order to maintain appropriate metabolic and nutritional conditions. In this study, we examined the developmental changes in the hypothalamic mRNA levels of brain-derived neurotrophic factor (BDNF), which is a potent anorectic factor and the changes in the sensitivity of the hypothalamic expression of this factor to fasting during the neonatal to pre-pubertal period. Under fed conditions, hypothalamic BDNF mRNA expression decreased during development in both male and female rats. Similarly, the serum levels of leptin, which is a positive regulator of hypothalamic BDNF expression, also tended to fall during the developmental period. The serum leptin level and the hypothalamic BDNF mRNA level were found to be positively correlated in both sexes under the fed conditions. Hypothalamic BDNF mRNA expression was decreased by 24h fasting (separating the rats from their mothers) in the early neonatal period (postnatal day 10) in both males and females, but no such changes were seen at postnatal day 20. Twenty-four hours' fasting (food deprivation) did not affect hypothalamic BDNF mRNA expression in the pre-pubertal period (postnatal day 30). On the other hand, the rats' serum leptin levels were decreased by 24h fasting (separating the rats from their mothers at postnatal day 10 and 20, and food deprivation at postnatal day 30) throughout the early neonatal to pre-pubertal period. The correlation between serum leptin and hypothalamic BDNF mRNA levels was not significant under the fasted conditions. It can be speculated that leptin partially regulates hypothalamic BDNF mRNA levels, but only in fed conditions. Such changes in hypothalamic BDNF expression might play a role in maintaining appropriate metabolic and nutritional conditions and promoting normal physical development. In addition, because maternal separation induces a negative energy balance and short- and long-term stress responses, it is also possible that reductions in hypothalamic BDNF mRNA levels in the early neonatal period (postnatal day 10) may be partially induced by stress responses of the maternal deprivation.

Feeding and food availability modulate brain-derived neurotrophic factor, an orexigen with metabolic roles in zebrafish

“…Nevertheless, the effects of fasting were opposite in the brain and liver, where it downregulates the expression of the BDNF system. A similar effect of fasting on BDNF was described in the mammalian brain 58,59 . Based on our observations, it is plausible that the increased expression of bdnf in the foregut (directly implicated in sensing the levels of food intake) is enough for eliciting an increase in food intake in fasting states, while the reduced expression in the brain and gut might correlate with other effects of BDNF.…”

Cannabinoid CB1/CB2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity‐based anorexia

“…Thus, the two variables manipulated in the ABA model were able to alter leptin signalling when applied separately. In agreement with this result, leptin levels have been shown to decrease in response to starvation or exercise Endocannabinoid system and activity-based anorexia BJP in both humans and rats (Ahima et al, 1996;Iwasa et al, 2016). It is very important to underline that both THC and CP treatments are able to significantly modify the reduced plasma leptin level exclusively in ABA rats that are exposed concomitantly to food restriction and exercise and not in Restricted and Exercise rats in which each variable is applied independently.…”

Leptin in depression: a potential therapeutic target

“…Growing evidence demonstrates a link between BDNF expression and regulation of metabolic balance. Food deprivation, characterized by lower leptin secretion, can reduces BDNF expression within the dorsal vagal complex (DVC) and hippocampus 95 , 96 . Leptin stimulates BDNF mRNA translation in the dendrites of hypothalamic neurons 97 .…”