Crosstalk between kisspeptin and gonadotropin-inhibitory hormone in the silence of puberty: preclinical evidence from a calcium signaling study.

Kisspeptin and gonadotropin-inhibitory hormone (GnIH) are among suggested neuroendocrine modulators of reproductive function. Intracellular calcium signaling is a critical component in the regulation of a variety of physiological and pathological processes including neurotransmitter release, and, therefore, can be used as signaling indicator for investigating the involvement of kisspeptin, GnIH, and gonadotropin-releasing hormone (GnRH) release. Hence, this study investigated the effects of kisspeptin and GnIH on calcium signaling using immortalized hypothalamic cells (rHypoE-8) as a model. Kisspeptin neurons were loaded with the ratiometric calcium dye (Fura-2 AM, 1 µmol) and intracellular free calcium ([Ca2+]i) responses were quantified using digital fluorescence imaging system. Kisspeptin-10 (100, 300, and 1000 nM) caused a significant increase in [Ca2+]i in rHypoE-8 cells (n = 58, n = 64, and n = 49, respectively, p < 0.001). The kisspeptin receptor antagonist, P234, inhibited the calcium responses to kisspeptin (p < 0.001, n = 32). GnIH (100 and 1000 nM), alone, did not cause any significant change in the mean basal [Ca2+]i levels in kisspeptin cells, but GnIH attenuated the kisspeptin-evoked [Ca2+]i transients (n = 47, p < 0.001). This novel findings of [Ca2+]i signaling in in vitro setting implicate that kisspeptin and GnIH may exert their effects on hypothalamus-pituitary-gonadal (HPG) axis by modulating kisspeptin neurons. These results also implicate that kisspeptin neurons may have an autocrine regulation.

Asprosin, a novel therapeutic candidate for painful neuropathy: an experimental study in mice.

Recent studies indicate presence of a strong link between adipokines and neuropathic pain. However, the effects of asprosin, a novel adipokine, on neuropathic pain have not been studied in animal models.Mouse models were employed to investigate the antinociceptive effectiveness of asprosin in the treatment of three types of neuropathic pain, with metabolic (streptozocin/STZ), toxic (oxaliplatin/OXA), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, respectively. Changes in nociceptive behaviors were assessed relative to controls using thermal (the hot plate and cold plate tests, at 50 °C and 4 °C respectively) and mechanical pain (von Frey test) tests after intraperitoneal (i.p.) administration of asprosin (10 µg/kg) and gabapentin (50 mg/kg) in several times intervals. Besides, possible effect of asprosin on the motor coordination of mice was assessed with a rotarod test. Serum level of asprosin was quantified by ELISA.In neuropathic pain models (STZ, OXA, and CCI), asprosin administration significantly reduced both mechanical and thermal hypersensitivity, indicating that it exhibits a clear-cut antihypersensitivity effect in the analyzed neuropathic pain models. The most effective time of asprosin on pain threshold was observed 60 min after its injection. Also, asprosin displayed no notable effect on the motor activity. Asprosin levels were significantly lower in neuropathic pain compared to healthy group (p < 0.05).The results yielded by the present study suggest that asprosin exhibits an analgesic effect in the neuropathic pain models and may have clinical utility in alleviating chronic pain associated with disease and injury originating from peripheral structures.