The potential role of the novel hypothalamic neuropeptides nesfatin-1, phoenixin, spexin and kisspeptin in the pathogenesis of anxiety and anorexia nervosa

Abstract

Due to the dynamic development of molecular neurobiology and bioinformatic methods several novel brain neuropeptides have been identified and characterized in recent years. Contemporary techniques of selective molecular detection e.g. in situ Real-Time PCR, microdiffusion and some bioinformatics strategies that base on searching for single structural features common to diverse neuropeptides such as hidden Markov model (HMM) have been successfully introduced. A convincing majority of neuropeptides have unique properties as well as a broad spectrum of physiological activity in numerous neuronal pathways including the hypothalamus and limbic system. The newly discovered but uncharacterized regulatory factors nesfatin-1, phoenixin, spexin and kisspeptin have the potential to be unique modulators of stress responses and eating behaviour. Accumulating basic studies revelaed an intriguing role of these neuropeptides in the brain pathways involved in the pathogenesis of anxiety behaviour. Nesfatin-1, phoenixin, spexin and kisspeptin may also distinctly affect the energy homeostasis and modulate food intake not only at the level of hypothalamic centres. Moreover, in patients suffered from anxiety and anorexia nervosa a significant, sex-related changes in the plasma neuropeptide levels occurred. It should be therefore taken into account that the targeted pharmacomodulation of central peptidergic signaling may be potentially helpful in the future treatment of certain neuropsychiatric and metabolic disorders. This article reviews recent evidence dealing with the hypothetical role of these new factors in the anxiety-related circuits and pathophysiology of anorexia nervosa.

Xiaoyaosan Ameliorates Chronic Immobilization Stress-Induced Depression-Like Behaviors and Anorexia in Rats: The Role of the Nesfatin-1–Oxytocin–Proopiomelanocortin Neural Pathway in the Hypothalamus

“…In addition, changes in appetite and weight are common diagnostic markers for major depressive disorder (4), and approximately 48% of adult depressed patients show depression-related loss of appetite (5). The induction of some anorexigenic peptides by stress has been associated with the pathogenesis of depression (6).…”

Phoenixin and Its Role in Reproductive Hormone Release

“…In addition to evidence demonstrating phoenixin and its effects on kisspeptin expression, phoenixin has also been observed to co-localize with a further neuropeptide, nesfatin. 17 Nesfatin-1 is a novel neuropeptide, whose expression has been described in the forebrain, hindbrain, brainstem, and spinal cord 18 with nesfatin-1 expressing neurons identified in the arcuate, paraventricular, and supraoptic nuclei. 18 Acting through an unidentified G-protein-coupled receptor, nesfatin is a satiety peptide with potent anorexigenic effects, playing an important role in glucose and energy homeostasis.…”

“…21 Given the similar distribution of phoenixin and nesfatin expression, and the known association between energy homeostasis and reproduction, Pałasz et al sought to determine whether these two neuropeptides were co-localized. 17 Utilizing immunohistochemical techniques, they were able to demonstrate in male Sprague-Dawley rats that more than 86% of phoenixin-immunoreactive arcuate neurons demonstrated coexpression with nesfatin-1, and that 70% of phoenixin-immunopositive cells co-localized with nefastin-1 in the paraventricular nucleus and hypothalamus, and 76% of phoenixin-immunopositive cells in the ventromedial hypothalamus also coexpressed nesfatin-1.…”

“…While the authors were not able to comment further on any physiological relationship between the two neuropeptides, it is important to note that they observed that their description of a novel population of phoenixin expressing neurons in the arcuate nucleus and ventromedial hypothalamus provides supportive evidence that phoenixin may be released into the median eminence and thus affect pituitary hormone secreting cells, in addition to being secreted into the general circulation via the hypophyseal portal system. 17 Further to the description of co-localization of nesfatin and phoenixin, animal and human studies have sought to identify whether phoenixin may modulate energy intake and feeding behaviors.…”

“…Recently, it has been hypothesized that given the effects of phoenixin on anxiety and feeding behaviors in animals, and the observation of a correlation with anxiety in humans, phoenixin may play a contributory role to the pathogenesis of eating disorders. 17 However, this remains a purely speculative hypothesis, and one that is yet to be tested.…”