Neurotransmissions of antidepressant-like effects of kisspeptin-13

Tanaka, Masaru; Csabafi, Krisztina; Telegdy, Gyula

doi:10.1016/j.regpep.2012.08.017

Cited by 53 publications

(66 citation statements)

References 18 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%

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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%

“…This indicates that Kiss1 does not return various parameters to controls but far exceeds them. This raises the possibility that the kisspeptin "reversal" of AS effects, as well as anxiolytic effect, could be partly occurring through an interaction of other neurotransmitters, such as adrenergic and cholinergic neurons (33,35).…”

Section: Discussionmentioning

confidence: 99%

Habenular kisspeptin modulates fear in the zebrafish

Ogawa

Nathan

Parhar

2014

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

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“…This is in keeping with the role of the prefrontal area in the internalisation of safety to reduce fear and anxiety to negative stimuli [45] and is an area known to express kisspeptin receptor mRNA in humans [20]. Furthermore, peripheral kisspeptin administration to healthy men reduces negative mood in psychometric tests compared to vehicle [40] consistent with the aforementioned study in rodents [44].…”

Section: Kisspeptin and Moodsupporting

confidence: 84%

“…1). During a forced swimming test in rodents designed to assess depressive behaviour, intracerebroventricular administration of kisspeptin dose-dependently reversed immobility, climbing, and swimming times suggesting antidepressant-like effects which were attenuated by pretreatment with 5-HT 2 and α 2 -adrenergic antagonists [44].…”

Section: Kisspeptin and Moodmentioning

confidence: 97%

“…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%

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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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Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder

et al. 2022

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ImportanceDespite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown.ObjectiveTo test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD.Design, Setting, and ParticipantsThis randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021.InterventionsA 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.Main Outcomes and MeasuresBlood oxygen level–dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli.ResultsOf the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P &lt; .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007). Kisspeptin’s enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects.Conclusions and RelevanceThese findings lay the foundations for clinical applications for kisspeptin in women with HSDD.Trial RegistrationISRCTN trial registry identifier: ISRCTN17271094

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Neurotransmissions of antidepressant-like effects of kisspeptin-13

Cited by 53 publications

References 18 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

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder

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