Effects of Galp and alarin peptides on HPA axis gene expression and adrenal function: In vivo experiments

Abstract

Background. Many experimental data indicate interactions between peptides involved in the control of food intake, energy homeostasis and adrenocortical hormone release. Glucocorticoids stimulate or inhibit the secretion of orexigenic and anorexigenic peptides, which in turn are involved in the regulation of adrenal growth, structure and function. Galanin-like peptide (Galp) and alarin (Ala) are involved in the regulation of food intake. Galp and Ala mRNAs have already been shown to be present in the arcuate nucleus (ARC) of the hypothalamus in both rats and mice.Objectives. To investigate the expression of Ala, Galp and their receptors in the hypothalamus and pituitary and adrenal glands of the rat hypothalamic-pituitary-adrenal (HPA) axis after intraperitoneal administration of peptides in vivo. Materials and methods.Experimental in vivo models were used: acute and long-term exposure to peptides.Results. The expression of Galp, Ala, their receptors, and steroidogenesis enzymes was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Statistically significant expression changes were found in the hypothalamus and pituitary after 1-hour exposure to the peptides, such as a decrease in corticotropin-releasing hormone (CRH) expression after Ala, Galp and adrenocorticotropic hormone (ACTH) administration, and a decrease in the expression of receptors for galanin (Gal) (Galr1 and Galr2). In the pituitary, there was a statistically significant increase in the expression of Ala, Galr1, Galr2, and Galr3 receptors 1 h after Galp administration. In the adrenal glands, only a statistically significant decrease in Galr2 expression was observed after 1 h of Ala 0.5 administration. The mRNA expression of steroidogenesis enzymes also changed: for example, the expression of cholesterol desmolase increased 24 h after Ala peptide administration. Conclusions.The results indicate that the peptides tested under in vivo conditions can alter the expression of the peptides tested, as well as of Galp, Ala and Gal receptors and steroidogenesis enzymes -Cyp11a1 (cholesterol desmolase), Cyp11b1 (11β-hydroxylase) and Cyp11b2 (aldosterone synthase).

Regulatory effects and potential therapeutic implications of alarin in depression, and arguments on its receptor

“…Zhuang et al consistently showed that central injection of alarin significantly ameliorates depression-like behaviors in the UCMS mouse model (28). Subsequently, the antidepressant properties of alarin were further confirmed by several other studies (11,27,66). However, the antidepressant-like effect of alarin has been shown to be dose-limited, with no remarkable effect at higher doses (at 2.0 nmol or higher).…”

“…Therapeutically, antagonists of galanin receptor (GalR) sub-type 1 (GalR1) and GalR3, as well as agonists of GalR2 have been established to have an antidepressant-like effect by enhancing the activities of selective serotonin reuptake inhibitors (SSRIs) and promoting the availability of transcription factors (64,65). Importantly, recent research has reported that alarin, which is also localized in the brain areas linked with depression, like the medial amygdala and hypothalamus, has been demonstrated to have regulatory effects on depression-like behaviors in various animal models (11,(25)(26)(27)66).…”

“…Another study also found that alarin negatively affects the expression of enzymes involved in steroidogenesis, such as cholesterol desmolase, 11β-hydroxylase, and aldosterone synthase, in the adrenal glands. In addition, although it has no appreciable effect on blood concentrations of aldosterone and CORT, alarin substantially reduces blood hormone levels derived from the HPA axis, such as CRH, ACTH, and pro-opiomelanocortin (POMC) (66). This effect of alarin resembles those of other antidepressants that reduce the elevated levels of ACTH, cortisol, and CORT in depressed subjects (106)(107)(108).…”

The evolving roles of alarin in physiological and disease conditions, and its future potential clinical implications

“…The restored synaptic proteins are essential for the formation, maturation, and function of synapses, thereby alleviating depression ( 78 – 83 ). Alarin is also postulated to have an antidepressant-like effect via the inhibition of the overactivated HPA axis and normalizing the serum levels of crucial glucocorticoid hormones ( 27 , 84 ). Moreover, alarin may help alleviate depression by increasing the expression of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus, which has antidepressant-like actions through neuroprotection and promoting synaptic plasticity ( 27 ).…”

Alarin potentiates ongoing epileptiform activity in rat brain slices: an in vitro electrophysiological study

“…Alarin is a recently discovered 25 amino acid neuropeptide belongs to galanin peptides family and it is a variant transcript of the GALP gene and has a wide distribution in the brain and periphery [6]. Alarin exerts its main function in physiological processes such as feeding and water intake by activating pathways in hypothalamus and pituitary gland [7,8]. Beside the autonomic contribution of alarin it also has extra hypothalamic in uences.…”