Effects of kisspeptin analogues on the behavior of <i>Danio rerio</i>
Abstract: BACKGROUND: Previously has been shown that fish kisspeptin 1 (Kiss1) acts on the brains serotonin system to reduce anxiety-phobic reactions in Danio rerio. The kissspeptin gene (kiss1) of teleost fish is also a conservative orthologue of the kissspeptin gene (KISS1/Kiss1) of mammals. AIM: In this work we investigated the possible anxiolytic effect of mammalian kisspeptin analogs Kiss1 in Danio rerio in comparison with antidepressants of the serotonin-type of action. MATERIALS AND METHODS: A novelty… Show more
Search citation statements
Paper Sections
Citation Types
Year Published
Publication Types
Relationship
Authors
Journals
Cited by 5 publications
References 34 publications
Reactive changes of kisspeptin-producing hypothalamic neuroendocrine cells during hypogonadism and its replacement therapy by the kisspeptin analogue in rats
BACKGROUND: This study is devoted to the morphological substantiation of the model of male hypogonadism and to establishing the effectiveness of its replacement therapy at the level of the central link of the hypothalamic-pituitary-testicular axis using morphological methods. Information about reactive changes in neuroendocrine cells that synthesize the peptide kisspeptin, which regulates the production of gonadoliberin when modeling male and female hypogonadism, has not been described in the literature, which prevents the creation of a micro-morphological basis for the development of models of hypogonadism and the implementation of further preclinical studies of the effectiveness of its replacement therapy. The goal is to carry out a morphological analysis of kisspeptin-producing neuroendocrine cells of the hypothalamus in normal conditions, with experimental hypogonadism and after replacement therapy. AIM: To carry out a morphological analysis of kisspeptin-producing neuroendocrine cells of the hypothalamus in normal conditions, with experimental hypogonadism and after replacement therapy. MATERIALS AND METHODS: The objects of the study were 3 groups of adult male Wistar rats 6–8 months of age. In animals of the first and second groups, after anesthesia, total ischemia of both testicles was caused by ligating the left and right spermatic cord with the vascular bundle of the testicle for 60 minutes. Rats of the second group, a few minutes after restoration of testicular blood flow, were given replacement therapy by daily administration of a synthetic analogue of kisspeptin KS6 for 7 days. Control animals of the third group were subjected to sham surgery. After 10 days, all animals were sacrificed, their brains were removed and embedded in paraffin. Nissl-stained frontal histological sections of the most massive areas of the kisspeptin-producing nuclei of the hypothalamus-periventricular and arcuate-were examined using the Imagescope program (Electronic Analysis, Russia). The number of cell bodies of viable and dead neurons was counted (under the control of immunohistochemical identification of the caspase-3 antigen), and the area of the body, nucleus and cytoplasm of viable cells was calculated. Statistical processing of the data was carried out using the GraphPad PRISM (USA) program to determine the median, upper and lower quartiles. Differences were considered significant at p 0.01. RESULTS: Simulation of acute ischemia caused a significant increase in the number of dead neurons, a slight decrease in the number of viable neurons and a decrease in the area of their cytoplasm in both kisspeptin-producing nuclei. As a result of KS6 replacement therapy, most neuronal cell bodies retained their original phenotype, but the number of dead neurons was high in both experimental groups. CONCLUSIONS: Modeling of male hypogonadism using the method of bilateral acute testicular ischemia induces death and partially reversible degenerative changes in kisspeptin-producing neuroendocrine cells of the hypothalamus. Neuropeptide KS6 has a pronounced restorative effect on kisspeptin-producing neurons of the hypothalamus, which is due to its specific activating effect on endocrine cells of all parts of the hypothalamic-pituitary-testicular axis.
Reactive changes of kisspeptin-producing hypothalamic neuroendocrine cells during hypogonadism and its replacement therapy by the kisspeptin analogue in rats
BACKGROUND: This study is devoted to the morphological substantiation of the model of male hypogonadism and to establishing the effectiveness of its replacement therapy at the level of the central link of the hypothalamic-pituitary-testicular axis using morphological methods. Information about reactive changes in neuroendocrine cells that synthesize the peptide kisspeptin, which regulates the production of gonadoliberin when modeling male and female hypogonadism, has not been described in the literature, which prevents the creation of a micro-morphological basis for the development of models of hypogonadism and the implementation of further preclinical studies of the effectiveness of its replacement therapy. The goal is to carry out a morphological analysis of kisspeptin-producing neuroendocrine cells of the hypothalamus in normal conditions, with experimental hypogonadism and after replacement therapy. AIM: To carry out a morphological analysis of kisspeptin-producing neuroendocrine cells of the hypothalamus in normal conditions, with experimental hypogonadism and after replacement therapy. MATERIALS AND METHODS: The objects of the study were 3 groups of adult male Wistar rats 6–8 months of age. In animals of the first and second groups, after anesthesia, total ischemia of both testicles was caused by ligating the left and right spermatic cord with the vascular bundle of the testicle for 60 minutes. Rats of the second group, a few minutes after restoration of testicular blood flow, were given replacement therapy by daily administration of a synthetic analogue of kisspeptin KS6 for 7 days. Control animals of the third group were subjected to sham surgery. After 10 days, all animals were sacrificed, their brains were removed and embedded in paraffin. Nissl-stained frontal histological sections of the most massive areas of the kisspeptin-producing nuclei of the hypothalamus-periventricular and arcuate-were examined using the Imagescope program (Electronic Analysis, Russia). The number of cell bodies of viable and dead neurons was counted (under the control of immunohistochemical identification of the caspase-3 antigen), and the area of the body, nucleus and cytoplasm of viable cells was calculated. Statistical processing of the data was carried out using the GraphPad PRISM (USA) program to determine the median, upper and lower quartiles. Differences were considered significant at p 0.01. RESULTS: Simulation of acute ischemia caused a significant increase in the number of dead neurons, a slight decrease in the number of viable neurons and a decrease in the area of their cytoplasm in both kisspeptin-producing nuclei. As a result of KS6 replacement therapy, most neuronal cell bodies retained their original phenotype, but the number of dead neurons was high in both experimental groups. CONCLUSIONS: Modeling of male hypogonadism using the method of bilateral acute testicular ischemia induces death and partially reversible degenerative changes in kisspeptin-producing neuroendocrine cells of the hypothalamus. Neuropeptide KS6 has a pronounced restorative effect on kisspeptin-producing neurons of the hypothalamus, which is due to its specific activating effect on endocrine cells of all parts of the hypothalamic-pituitary-testicular axis.
In our previous work, we suggested that analogues of mammalian kisspeptin Kiss1 reduce anxiety-phobic reactions to novelty in Danio rerio. The most effective dose for the action of the studied analogues of kisspeptin corresponded to 0.1 mg per 1000 ml of water. In this work, it was shown that other analog of mammalian kisspeptin Kiss1 at a dose of 0.1 mg per 1000 ml of water also reduced the anxious behavior of Danio fish. The effect of Kiss 1 and Kiss 2 kisspeptins on the behavior of Danio rerio was also evaluated. In the novel test it was revealed that the number of freezings decreased by 2 times against the background of the introduction of kisspeptin 10, and by 3 times after the introduction of the analogue of kisspepin. An analogue of mammalian kisspeptin reduced the freezing time by 2 times. The length of the trajectory decreased by 2 times under the influence of the mammalian Kiss 1 analogue of kisspeptin. Also, against the background of the action of kisspeptin 10, the number of transitions to the upper part of the tank increased by 2 times. After the introduction of the kisspeptin analogue, the number of transitions to the upper part of the aquarium increased by 3 times. In the predator test, the number and time of freezings decreased by 1.5 times against the background of the action of mammalian kisspeptins. The length of the trajectory after the introduction of kisspeptin bony fish and kisspeptin 10 mammals increased. The length of the trajectory after the introduction of Kiss1 increased by 1.5 times. The length of the trajectory after the introduction of Kiss2 increased by 3 times. After the introduction of kisspeptin 10, the trajectory increased by 2 times, and the time spent in the lower part of the tank decreased by 2 times. Kisspeptins of bony fish also reduced anxiety-phobic reactions in fish, but to a lesser extent. Thus, kisspeptin 10 and an analogue of mammalian kisspeptin in response to the presentation of a predator had more significant effects on anxiety in Danio rerio compared to the action of kisspeptin bony fish Kiss 1 and Kiss 2. It is concluded that bony fish kisspeptins and mammalian kisspeptins can reduce anxiety-phobic reactions in Danio rerio, but mammalian kisspeptins are most effective. Bony fish kisspeptin Kiss 1 has an anxiolytic effect in contrast to Kiss 2, which suggests that it affects the reduction of fear, and Kiss 2 seems to be responsible for social and sexual behavior. The results support the hypothesis that kisspeptins may be involved in the regulation of anxiety-phobic states, apparently to maintain the emotional aspects of reproductive behavior, such as sexual motivation and arousal.
Study of the effects of kisspeptin analogs on the behavior of<i> Danio rerio</I>
The neuropeptide kisspeptin is currently most widely known as a regulator of mammalian sexual behavior. For pharmacological analysis, mammalian Kiss1 kisspeptin analogues were used, Clone (USA): KS4, KS5, KS6, KS7, KS8, KS9 and Kiss 10. Kisspeptins were dissolved in aquarium water and applied in two doses: 1). 0.01 mg per 1000 ml of water; 2). 0.1 mg per 1000 ml of water. Phenazepam was dissolved in water and used in three doses: 1) 0.1 mg per 1000 ml of water; 2) 0.5 mg per 1000 ml of water; 3) 1 mg per 1000 ml of water. This paper compares kisspeptines with anxiolytics using phenazepam as an example in the novelty test. It was shown that in response to the novelty of being placed in the viewing tank, fish responded by diving to the bottom, increasing freesing, and decreasing the number of movements to the upper half of the tank. Fish residence time in the lower part of the tank after administration of phenazepepam decreased, especially when used at a dose of 0.5 and 1 mg/liter. Kisspeptin analogues decreased the indices characterizing the anxious state of the fish. Against the background of Kiss1 kisspeptin analogues, the average fish path length differed significantly in contrast to the effects of phenazepam. KS 4 at a dose of 0.1 mg/L showed a 1.4-fold decrease in the number of freesing, 1.4-fold decrease in the freesing time and 1.4-fold decrease in the trajectory length. The number of transitions to the upper part of the tank increased 1.5 times. The dose of 0.01 mg/l decreased the number of freesing by 1.5 times, freesing time by 1.5 times, trajectory length by 3 times. KS 5 at a dose of 0.1 mg/L decreased the number of freesings by a factor of 1.6, the freesing time by a factor of 1.6, and the trajectory length by a factor of 1.17. The number of transitions to the upper part of the tank increased 1.5 times. The dose of 0.01 mg/l decreased the number of freesing by 3 times, freesing time by 2.8 times, trajectory length by 2.8 times. KS 6 at a dose of 0.1 mg/l decreased the number of freesings by 2.7 times, the freesing time by 2 times, and the trajectory length by 2.5 times. The number of transitions to the upper part of the aquarium increased 2.5 times. The dose of 0, 01 mg/ml decreased the number of freesing by 2.6 times, freesing time by 2.6 times, trajectory length by 1.7 times. KS 7 at a dose of 0.1 mg/L decreased the number of freesing by a factor of 1.7, freesing time by a factor of 1.4, and trajectory length by a factor of 1.3. The number of movements to the top of the aquarium increased 1.6-fold. The dose of 0.01 mg/l decreased the number of freesing by 1.7 times, freesing time by 1.4 times, trajectory length by 1.6 times. KS8 at a dose of 0.1 mg/L decreased the number of freesings by 1.6 times, the freesing time by 1.7 times, and the trajectory length by 1.6 times. The dose of 0.01 mg/l decreased the number of freesing by 2.3 times, the freesing time by 2.2 times, and the trajectory length by 1.8 times. KS9 at a dose of 0.1 mg/l decreased the number of freesing by 2.2 times, the freesing time by 2.2 times, and the trajectory length by 1.2 times. The dose of 0.01 mg/L reduced the number of freesings by 1.5 times, the freesing time by 1.5 times, and the trajectory length by 1.6 times. In Kiss 10 at a dose of 0.1 mg/L, there was a 1.6-fold decrease in the number of frizzings, a 1.5-fold decrease in freezing time, and a 1.4-fold decrease in trajectory length. There was a 2.7-fold increase in the transitions to the upper part of the aquarium. The dose of 0.01 mg/l decreased the number of freesing by 1.7 times, freesing time by 1.6 times, trajectory length by 1.3 times. We observed a 1.3-fold increase in the number of trajectories. Summarizing the obtained indicators, we came to the conclusion that kisspeptin analogues were not inferior in their effect to the effects obtained after taking the tranquilizer phenazepam. Among mammalian kisspeptin analogues, KS6 at a dose of 0.1 mg/L showed the best performance. It is concluded that mammalian Kiss1 kisspeptin analogues and Kiss 10 reduce anxiety-phobic reactions to novelty in Danio rerio. At the same time, the effects of the studied kisspeptin analogues are lower than those of phenazepam. Kisspeptin is involved not only in the modulation of 5-HT-dependent behavior in Danio rerio, but also in the GABA-ergic system as benzodiazepine-type tranquilizers. The results support the hypothesis that kisspeptin may be involved in the regulation of anxiety-phobic states, apparently to maintain the emotional aspects of reproductive behavior, such as sexual motivation and arousal.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
Contact Info
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Product
Resources
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.
