Marino Marianna, Di Pietro Paola, D'Auria Raffaella, Lombardi Martina, Pastorino Grazia Maria Giovanna, Troisi Jacopo, Operto Francesca Felicia, Carrizzo Albino, Vecchione Carmine, Viggiano Andrea, Meccariello Rosaria, Santoro Antonietta
Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.
Child and Adolescent Neuropsychiatry Unit, San Giovanni di Dio Ruggi d'Aragona Hospital, 84131 Salerno, Italy.
Int J Mol Sci. 2025 Apr 23;26(9):3977. doi: 10.3390/ijms26093977.
Neurogenesis is considered the most robust form of plasticity in the adult brain. To better decipher this process, we evaluated the potential crosstalk of Kisspeptin and Endocannabinoid Systems (KPS and ECS, respectively) on hippocampal neurogenesis. Male adolescent rats were exposed to kisspeptin-10 (KP10) and the endocannabinoid anandamide (AEA) administered alone or in combination with the type 1 cannabinoid receptor (CB1R) antagonist SR141716A. The expression of Kiss1 and Kisspeptin receptor (Kiss1R) has been characterized for the first time in rat hippocampus together with the expression of the CB1R and the Transient Receptor Potential Vanilloid 1 ion channel receptor (TRPV1). Results show that both systems inhibit neurogenesis by reducing the extracellular signal-regulated kinase (ERK) signaling. Despite little differences in the expression of Kiss1R and CB1R, TRPV1 is enhanced by both KP10 and AEA treatments, suggesting TRPV1 as a common thread. KP10 administration reduces CB1R expression in the dentate gyrus, while AEA does not. KPS, unlike ECS, promotes the expression of estrogen receptor α (ER-α) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), also upregulating sirtuin 1 (SIRT1), brain-derived-neurotrophic factor (BDNF), and c-Jun. These findings suggest that the interaction between ECS and KPS could be involved in the fine-tuning of neurogenesis, highlighting a novel role for KPS.
神经发生被认为是成年大脑中最强大的可塑性形式。为了更好地解读这一过程，我们评估了亲吻素和内源性大麻素系统（分别为KPS和ECS）对海马神经发生的潜在相互作用。雄性青春期大鼠分别单独或与1型大麻素受体（CB1R）拮抗剂SR141716A联合接受亲吻素-10（KP10）和内源性大麻素花生四烯乙醇胺（AEA）处理。首次对大鼠海马中Kiss1和亲吻素受体（Kiss1R）的表达以及CB1R和瞬时受体电位香草酸亚型1离子通道受体（TRPV1）的表达进行了表征。结果表明，这两个系统均通过降低细胞外信号调节激酶（ERK）信号传导来抑制神经发生。尽管Kiss1R和CB1R的表达差异不大，但TRPV1在KP10和AEA处理后均增强，表明TRPV1是一个共同因素。给予KP10可降低齿状回中CB1R的表达，而AEA则无此作用。与ECS不同，KPS促进雌激素受体α（ER-α）和甘油醛-3-磷酸脱氢酶（GAPDH）的表达，同时上调沉默调节蛋白1（SIRT1）、脑源性神经营养因子（BDNF）和c-Jun。这些发现表明，ECS和KPS之间的相互作用可能参与神经发生的微调，突显了KPS的新作用。
