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Published in: Brain Structure and Function 7/2021

Open Access 01-09-2021 | Cannabinoid | Original Article

Expression of type one cannabinoid receptor in different subpopulation of kisspeptin neurons and kisspeptin afferents to GnRH neurons in female mice

Authors: Tamás Wilheim, Krisztina Nagy, Mahendravarman Mohanraj, Kamil Ziarniak, Masahiko Watanabe, Joanna Sliwowska, Imre Kalló

Published in: Brain Structure and Function | Issue 7/2021

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Abstract

The endocannabinoids have been shown to target the afferents of hypothalamic neurons via cannabinoid 1 receptor (CB1) and thereby to influence their excitability at various physiological and/or pathological processes. Kisspeptin (KP) neurons form afferents of multiple neuroendocrine cells and influence their activity via signaling through a variation of co-expressed classical neurotransmitters and neuropeptides. The differential potency of endocannabinoids to influence the release of classical transmitters or neuropeptides, and the ovarian cycle-dependent functioning of the endocannabinoid signaling in the gonadotropin-releasing hormone (GnRH) neurons initiated us to study whether (a) the different subpopulations of KP neurons express CB1 mRNAs, (b) the expression is influenced by estrogen, and (c) CB1-immunoreactivity is present in the KP afferents to GnRH neurons. The aim of the study was to investigate the site- and cell-specific expression of CB1 in female mice using multiple labeling in situ hybridization and immunofluorescent histochemical techniques. The results support that CB1 mRNAs are expressed by both the GABAergic and glutamatergic subpopulations of KP neurons, the receptor protein is detectable in two-thirds of the KP afferents to GnRH neurons, and the expression of CB1 mRNA shows an estrogen-dependency. The applied estrogen-treatment, known to induce proestrus, reduced the level of CB1 transcripts in the rostral periventricular area of the third ventricle and arcuate nucleus, and differently influenced its co-localization with vesicular GABA transporter or vesicular glutamate transporter-2 in KP neurons. This indicates a gonadal cycle-dependent role of endocannabinoid signaling in the neuronal circuits involving KP neurons.
Literature
go back to reference Bardoczi Z, Wilheim T, Skrapits K, Hrabovszky E, Racz G, Matolcsy A, Liposits Z, Sliwowska JH, Dobolyi A, Kallo I (2018) GnRH neurons provide direct input to hypothalamic tyrosine hydroxylase immunoreactive neurons which is maintained during lactation. Front Endocrinol (lausanne) 9:685. https://doi.org/10.3389/fendo.2018.00685CrossRef Bardoczi Z, Wilheim T, Skrapits K, Hrabovszky E, Racz G, Matolcsy A, Liposits Z, Sliwowska JH, Dobolyi A, Kallo I (2018) GnRH neurons provide direct input to hypothalamic tyrosine hydroxylase immunoreactive neurons which is maintained during lactation. Front Endocrinol (lausanne) 9:685. https://​doi.​org/​10.​3389/​fendo.​2018.​00685CrossRef
go back to reference Brents LK (2016) Marijuana, the endocannabinoid system and the female reproductive system. Yale J Biol Med 89(2):175–191PubMedPubMedCentral Brents LK (2016) Marijuana, the endocannabinoid system and the female reproductive system. Yale J Biol Med 89(2):175–191PubMedPubMedCentral
go back to reference Di S, Malcher-Lopes R, Halmos KC, Tasker JG (2003) Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J Neurosci 23(12):4850–4857CrossRef Di S, Malcher-Lopes R, Halmos KC, Tasker JG (2003) Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J Neurosci 23(12):4850–4857CrossRef
go back to reference Hrabovszky E, Molnar CS, Sipos MT, Vida B, Ciofi P, Borsay BA, Sarkadi L, Herczeg L, Bloom SR, Ghatei MA, Dhillo WS, Kallo I, Liposits Z (2011) Sexual dimorphism of kisspeptin and neurokinin B immunoreactive neurons in the infundibular nucleus of aged men and women. Front Endocrinol (lausanne) 2:80. https://doi.org/10.3389/fendo.2011.00080CrossRef Hrabovszky E, Molnar CS, Sipos MT, Vida B, Ciofi P, Borsay BA, Sarkadi L, Herczeg L, Bloom SR, Ghatei MA, Dhillo WS, Kallo I, Liposits Z (2011) Sexual dimorphism of kisspeptin and neurokinin B immunoreactive neurons in the infundibular nucleus of aged men and women. Front Endocrinol (lausanne) 2:80. https://​doi.​org/​10.​3389/​fendo.​2011.​00080CrossRef
go back to reference Hrabovszky E, Wittmann G, Kallo I, Fuzesi T, Fekete C, Liposits Z (2012) Distribution of type 1 cannabinoid receptor-expressing neurons in the septal-hypothalamic region of the mouse: colocalization with GABAergic and glutamatergic markers. J Comp Neurol 520(5):1005–1020. https://doi.org/10.1002/cne.22766CrossRefPubMed Hrabovszky E, Wittmann G, Kallo I, Fuzesi T, Fekete C, Liposits Z (2012) Distribution of type 1 cannabinoid receptor-expressing neurons in the septal-hypothalamic region of the mouse: colocalization with GABAergic and glutamatergic markers. J Comp Neurol 520(5):1005–1020. https://​doi.​org/​10.​1002/​cne.​22766CrossRefPubMed
go back to reference Porteous R, Petersen SL, Yeo SH, Bhattarai JP, Ciofi P, de Tassigny XD, Colledge WH, Caraty A, Herbison AE (2011) Kisspeptin neurons co-express met-enkephalin and galanin in the rostral periventricular region of the female mouse hypothalamus. J Comp Neurol 519(17):3456–3469. https://doi.org/10.1002/cne.22716CrossRefPubMed Porteous R, Petersen SL, Yeo SH, Bhattarai JP, Ciofi P, de Tassigny XD, Colledge WH, Caraty A, Herbison AE (2011) Kisspeptin neurons co-express met-enkephalin and galanin in the rostral periventricular region of the female mouse hypothalamus. J Comp Neurol 519(17):3456–3469. https://​doi.​org/​10.​1002/​cne.​22716CrossRefPubMed
Metadata
Title
Expression of type one cannabinoid receptor in different subpopulation of kisspeptin neurons and kisspeptin afferents to GnRH neurons in female mice
Authors
Tamás Wilheim
Krisztina Nagy
Mahendravarman Mohanraj
Kamil Ziarniak
Masahiko Watanabe
Joanna Sliwowska
Imre Kalló
Publication date
01-09-2021
Publisher
Springer Berlin Heidelberg
Published in
Brain Structure and Function / Issue 7/2021
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-021-02339-z

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