Effects of kisspeptin-13 on the hypothalamic-pituitary-adrenal axis, thermoregulation, anxiety and locomotor activity in rats

Csabafi, Krisztina; Jászberényi, Miklós; Bagosi, Zsolt; Lipták, Nándor; Telegdy, Gyula

doi:10.1016/j.bbr.2012.11.039

Cited by 56 publications

(73 citation statements)

References 63 publications

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“…In the novel tank diving test, we also found some anxiolytic effects of Kiss1 (increase in top-to-bottom transitions) and an increase in 5-HT-related genes by Kiss1 administration. This is in good agreement with the antidepressant-like effects and stimulation of locomotor activities by kisspeptin-13 reported in rodents (33,34). In addition, cross-referencing between treatments (Figs.…”

Section: Discussionsupporting

confidence: 90%

Habenular kisspeptin modulates fear in the zebrafish

Ogawa

Nathan

Parhar

2014

Proc. Natl. Acad. Sci. U.S.A.

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Kisspeptin, a neuropeptide encoded by the KISS1/Kiss1, and its cognate G protein-coupled receptor, GPR54 (kisspeptin receptor, Kiss-R), are critical for the control of reproduction in vertebrates. We have previously identified two kisspeptin genes (kiss1 and kiss2) in the zebrafish, of which kiss1 neurons are located in the habenula, which project to the median raphe. kiss2 neurons are located in the hypothalamic nucleus and send axonal projections to gonadotropin-releasing hormone neurons and regulate reproductive functions. However, the physiological significance of the Kiss1 expressed in the habenula remains unknown. Here we demonstrate the role of habenular Kiss1 in alarm substance (AS)-induced fear response in the zebrafish. We found that AS-evoked fear experience significantly reduces kiss1 and serotonin-related genes (plasmacytoma expressed transcript 1 and solute carrier family 6, member 4) in the zebrafish. Furthermore, Kiss1 administration suppressed the AS-evoked fear response. To further evaluate the role of Kiss1 in fear response, zebrafish Kiss1 peptide was conjugated to saporin (SAP) to selectively inactivate Kiss-R1-expressing neurons. The Kiss1-SAP injection significantly reduced Kiss1 immunoreactivity and c-fos mRNA in the habenula and the raphe compared with control. Furthermore, 3 d after Kiss1-SAP injection, the fish had a significantly reduced AS-evoked fear response. These findings provide an insight into the role of the habenular kisspeptin system in inhibiting fear.5-HT | interpeduncular | neuroendocrine | anxiolytic K isspeptin, a hypothalamic neuropeptide derived from the KISS1/Kiss1, with the ability to activate the kisspeptin receptor (Kiss-R), has proven to play a key role in vertebrate reproduction (1). Kisspeptin neurons are present in the hypothalamic region, but their neural targets are not restricted to the hypothalamic region (2, 3). Furthermore, recent studies in mammals have revealed the expression of Kiss1 in several brain regions, including the medial amygdala (4). However, the knowledge of the potential role of kisspeptin-Kiss-R in nonhypothalamic regions remains limited. Using the teleost fish, we have previously identified two homologous genes (kiss1 and kiss2) encoding kisspeptin (5), of which kiss1 is a conserved ortholog of mammalian KISS1/Kiss1, whereas kiss2 has been found in hypothalamic nuclei of only nonmammalian vertebrates, which include amphibians and teleosts (6). In the zebrafish, kiss1 and kissr1 mRNAs are predominantly expressed in the ventral habenula (vHb) (5, 7). In nonmammalian vertebrates, the dorsal habenula (dHb) and the vHb are homologous to the medial (mHb) and lateral (lHb) habenula in mammals (8, 9). The lHb in primates regulates punishment avoidance behavior (10) and in rodents, it controls anxiety and fear (11), which suggests that nonmammalian vHb, homologous to the mammalian lHb, could modulate fear response. Furthermore, the vHb projects Kiss1 neuronal fibers to the median raphe (MR) (7, 12), a site adjacent to serotonergic (5-hydroxytrypt...

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Section: Discussionsupporting

confidence: 90%

Habenular kisspeptin modulates fear in the zebrafish

Ogawa

Nathan

Parhar

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…The functional data regarding kisspeptin's role in anxiety is perhaps less clear. Intracerebroventricular kisspeptin injection in male rodents decreased time spent in the open arms of a maze, suggesting that kisspeptin administration increases anxiety [42]. By contrast, a more recent study observed that DREADD activation of medial amygdala kisspeptin neurones in male rodents increased time in the open arms of a maze suggesting a decrease in anxiety [31].…”

Section: Kisspeptin and Moodmentioning

confidence: 89%

“…This included the anterior and posterior cingulate, amygdala, thalamus, and globus pallidus, which are all implicated in romantic, maternal, and unconditional love [53][54][55][56] and consistent with structures known to be involved in kisspeptin signalling in humans [19,20] and rodents [10,15,21,23,24]. Interestingly, kisspeptins enhanced activation of the amygdala in response to bonding images correlated with improved positive mood [40], a Sexual behaviours -Enhances limbic and paralimbic brain activity with correlations to reward, sexual aversion, and positive mood (H) [40] -Triggers erections (R) [51] Fear -Reduces fear responses (Z) [36][37][38]43] Social behaviours -MeA kisspeptin neurone apposition with dopaminergic and vasopressinergic neurones (R) [24] Audition -Male rodent ultrasonic vocalisations increase female ARC kisspeptin activity which correlates to the duration of female searching for male (R) [34] Mood -Antidepressant-like effects (R, H) [40,44] -Anxiolytic effects (R, Z) [31,36] -Anxiogenic effects (R) [42] Olfaction -Kisspeptin anatomical framework (R, H) [24] -Kiss1r and MeA Kiss1 roles in male olfactory partner preference (R) [30,31] -Opposite-sex urinary odours stimulate RP3V and limbic kisspeptin neurones and enhance LH surge (R) [32,33] Kisspeptin signalling potential mechanism that may contribute to the desire to bond with a partner.…”

Section: Kisspeptin and Sexual Processingmentioning

confidence: 99%

Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Comninos

Dhillo

2017

Neuroendocrinology

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The emergence of kisspeptin as a crucial regulator of the hypothalamo-pituitary-gonadal (HPG) axis over the last 14 years has answered many questions as to the control of reproductive hormone secretion from the hypothalamus. More recently, the role of kisspeptin outside the HPG axis has received increasing attention in the hope of delineating the pathways linking various sensory and social behaviours to reproduction. These studies, in a range of species from zebrafish to humans, have identified a role for kisspeptin in behavioural networks related to reproduction including olfaction, audition, fear, anxiety, mood, and sexual arousal. The available evidence suggests that extrahypothalamic kisspeptin signalling encourages positive aspects of emotional and sexual brain processing in a presumed drive towards reproduction and ultimately maintenance of the species at a population level. In this review, we examine these studies, which collectively propose that kisspeptin may integrate sexual and emotional brain processing with the control of the HPG axis.

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“…In the present study, CMS resulted in higher ACTH and CORT levels and higher expression of CRH gene in hypothalamus tissue in the HFD group compared to that in the control group, suggesting that HFD may enhance HPA axis sensitivity to chronic stress. Considerable evidence suggested associations between certain psychiatric disorders and HPA axis alterations, such as elevated glucocorticoid levels (10,(41)(42)(43). Furthermore, several psychiatric disorders associated with HPA dysfunction arise in obese teenagers, who are more prone to develop depression than adults (44).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic-pituitary-adrenal axis hypersensitivity in female rats on a post-weaning high-fat diet after chronic mild stress

Yang

Qian

2017

Experimental and Therapeutic Medicine

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Abstract.A high-fat diet (HFD) is highly correlated to obesity, metabolic diseases and certain behavioral changes. However, the effects of post-weaning HFD in rats during puberty and the role of the hypothalamic-pituitary-adrenal (HPA) axis in this process have remained elusive. The present study hypothesized that the HPA axis mediates the behavioral alterations induced by a post-weaning HFD. To investigate this, female rats were divided into two groups, one of which was fed a HFD from postnatal weeks (PWs) 4-12, while the other group received standard chow. Rats in each group were then subdivided into two subgroups each, and from PW 9-12, animals from one of the two subgroups were subjected to chronic mild stress (CMS), while the other subgroup received no stress. At PW 12, the body weight of rats receiving a HFD but no DMS was significantly higher than that in the control group. The frequency of crossing and rearing in the open field test and the time in the center of the Y-maze were decreased following CMS. Total time to escape was decreased in rats receiving HFD and after CMS. The serum levels of adrenocorticotropic hormone and corticosterone were increased in rats receiving an HFD and after CMS, and the mRNA levels of corticotropin-releasing hormone and arginine vasopressin in the hypothalamus were increased in the HFD + CMS group compared to that in the control group. The mRNA expression of glucocorticoid receptor (GR) in the hippocampi of rats in the HFD + CMS group was significantly decreased and the mineralocorticoid receptor/GR ratio was increased compared to that in the groups receiving either CMS or a HFD. In conclusion, these results indicated that female rats fed a post-weaning HFD showed HPA axis hypersensitivity under CMS, which may mediate behavioral alterations.

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Effects of kisspeptin-13 on the hypothalamic-pituitary-adrenal axis, thermoregulation, anxiety and locomotor activity in rats

Cited by 56 publications

References 63 publications

Habenular kisspeptin modulates fear in the zebrafish

Habenular kisspeptin modulates fear in the zebrafish

Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Hypothalamic-pituitary-adrenal axis hypersensitivity in female rats on a post-weaning high-fat diet after chronic mild stress

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