Impaired hypothalamic cocaine‐ and amphetamine‐regulated transcript expression in lateral hypothalamic area and paraventricular nuclei of dehydration‐induced anorexic rats

Abstract

Negative energy balance promotes physiological adaptations that ensure the survival of animals. The hypothalamic-pituitary-thyroid axis regulates basal energy expenditure and its down-regulating adaptation to negative energy balance is well described: in fasting, the serum content of thyrotrophin (TSH) and thyroid hormones (TH) decreases, enhancing the survival odds of individuals. By contrast, dehydration-induced anorexic (DIA) rats present an impaired hypothalamic-pituitary-thyroid (HPT) axis adaptation despite their negative energy balance: increased circulating TSH levels. The implication of cocaine- and amphetamine-regulated transcript (CART), an anorexic peptide, in HPT axis function impairment and food-avoidance behaviour displayed by DIA animals is unknown. Because CART is co-expressed with the peptide that regulates the HPT axis in hypophysiotrophic paraventricular nucleus (PVN) neurones (TSH-releasing hormone), we analysed CART expression and possible implications with respect to high TSH levels of DIA animals. We examined whether changes in CART expression from the lateral hypothalamic area (LHA) and arcuate nucleus (ARC) could participate in food-avoidance of DIA rats. DIA and forced-food restricted (FFR) animals reduced their body weight and food intake. FFR rats had a down-regulation of their HPT axis (reduced serum TH and TSH content), whereas DIA animals had reduced TH but increased TSH levels. CART mRNA expression in the ARC decreased similarly between experimental groups and diminished in anterior, medial PVN and in LHA of FFR animals, whereas DIA animals showed unchanged levels. This impaired CART mRNA expression in the anterior PVN and LHA could be related to the aberrant feeding behaviour of DIA rats but not to their deregulated HPT axis function.

The physiological control of eating: signals, neurons, and networks

“…Although details of how osmolality interacts with the upper brainstem eating control network to suppress eating are still unknown, attenuated Fos responses to 2DG in the pre-autonomic part of the PVH and particularly in the LHA suggest key roles for these two regions (506). LHA CART and LHA ORX neurons may contribute to the progression and reversal of DE-anorexia (507,508). But of particular interest is that a subset of an extensive and heterogenous GABA/neurotensin (NT) population in the LHA (see Section V E 2 b-v for more details) is well-placed to contribute by virtue of their ability to suppress food intake when stimulated chemogenetically (509).…”

“…In addition, the neurochemical makeup of LHA neurons is highly complex. For example, depending on their location some LHA MCH neurons also synthesize CART (656), while LHA NT neurons are plastic and varied with regards to their peptide configuration (508,657). These factors greatly complicate our understanding of how the LHA controls eating behaviors.…”

Glial cells in anorexia

“…The survival rate of the individual enhances as the serum content of thyrotropin and thyroid hormones decreases. This adaptation is observed in the FFR group, but HPT axis function fails to decrease and thyrotropin levels remain high in the DIA group of rats ( Jaimes-Hoy et al, 2008 ; García-Luna et al, 2010 , 2017 ). On the other hand, decreased leptin, estradiol, insulin, thyroid hormones and POMC expression, together with increased Neuropeptide Y and corticosterone serum levels, are common metabolic changes observed in FFR and DIA experimental groups ( Jaimes-Hoy et al, 2008 ; García-Luna et al, 2010 , 2017 ).…”