Useful Effects of Melatonin in Peripheral Nerve Injury and Development of the Nervous System

Uyanıkgil, Yiğit; Çavuşoğlu, Türker; Kılıç, Kubilay Doğan; Yiğittürk, Gürkan; Çelik, Servet; Tubbs, R. Shane; Turğut, Mehmet

doi:10.1055/s-0036-1597838

Cited by 19 publications

(11 citation statements)

References 43 publications

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“…The present study demonstrated that the melatonin treatment induced an increase in the number of nerve fibers, which was supported by findings of Uyanikgil et al (2017) who proved that melatonin affected the morphological features of nerve tissue and has a neuroprotective role through involvement in regeneration of peripheral nerves. Moreover, melatonin exerted a positive effect on axon length and development after peripheral nerve stress.…”

Section: Discussionsupporting

confidence: 91%

Melatonin Elicits Stimulatory Action on the Adrenal Gland of Soay Ram: Morphometrical, Immunohistochemical, and Ultrastructural Study

2017

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Endogenous melatonin is a hormone secreted by pineal gland; it has several roles in metabolism, reproduction, and remarkable antioxidant properties. Studies on the melatonin effect on the adrenal glands which are important endocrine organs, controlling essential physiological functions, are still deficient. In this study, we attempted to investigate the effect of exogenous melatonin treatment on the adrenal cortex and medulla using several approaches. Adrenal glands of 15 Soay ram were examined to detect the effect of melatonin treatment. Our results revealed that the cells of adrenal cortex of the treated animals were separated by wide and numerous blood sinusoids and showed signs of increase steroidogenic activity, which are evidenced by functional hypertrophy with increase profiles of mitochondria, smooth endoplasmic reticulum, and lipid droplets. The most striking ultrastructural features in the medulla of the treated group were the engorgement of chromaffin cells with enlarged secretory granules enclosed within a significantly increased diameter of these cells. The cytoplasm of these cells showed numerous mitochondria, rough endoplasmic reticulum (rER), Golgi apparatus, lysosomes, and glycogen granules. Exocytosis of secretory granules to the lumen of blood vessels was evident in the treated group. Piecemeal degranulation mode of secretion was recorded after melatonin treatment. Chromaffin cells in the control group expressed moderate immunoreactivity to Synaptophysin and tyrosine hydroxylase, compared with intensified expression after melatonin treatment. The ganglion cells of the melatonin-treated group showed a significant increase in diameter with numerous rER. The most interesting feature in this study is the presence of small granule chromaffin cells (SGC) and telocytes (TCs) for the first time in the adrenal glands of sheep. Moreover, these SGC cells, Schwann cells, fibroblasts, and progenitor stem cells showed a stimulatory response. The TCs were small branched cells scattered in the adrenal glands around cortical cells, chromaffin cells, nerve fibers, and blood vessels. These cells increased significantly in number, length of their telopodes, and secretory activity after melatonin treatment. In addition, multiple profiles of unmyelinated nerve fibers were demonstrated in all treated specimens. These results indicated that melatonin treatment caused a stimulatory action on all cellular and neuronal elements of the adrenal gland. This study may act as a new direction for treatment of adrenal insufficiency.

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Section: Discussionsupporting

confidence: 91%

Melatonin Elicits Stimulatory Action on the Adrenal Gland of Soay Ram: Morphometrical, Immunohistochemical, and Ultrastructural Study

2017

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“…Although MLT receptor agonists are approved for the treatment of sleep and depressive disorders, none of them have been yet approved for the treatment of NP. However, many promising pre-clinical findings suggest that MLT and its receptor agonists have a strong potential in managing chronic pain conditions 5–9…”

Section: Introductionmentioning

confidence: 99%

<p>Melatonin MT2 receptor agonist IIK-7 produces antinociception by modulation of ROS and suppression of spinal microglial activation in neuropathic pain rats</p>

Kuthati

Davuluri

Yang

et al. 2019

JPR

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Background In recent years, several melatonin (MLT) receptor agonists have been approved by FDA for the treatment of sleep disorders and depression. Very few studies have shed light on their efficacy against neuropathic pain (NP). IIK-7 is an MT-2 agonist known to promote sleep. Whether IIK-7 suppresses NP has not been reported, and the signaling profile is unknown. Objective To investigate the effect of melatonin type 2 receptor agonist IIK-7 on partial sciatic nerve transection-induced NP in rats and elucidate the underlying molecular mechanisms. Methods NP was induced by the PSNT in the left leg of adult male Wistar rats. On post-transection day 7, rats were implanted with intrathecal (i.t) catheter connected to an infusion pump and divided in to four groups: sham-operated/vehicle, PSNT/vehicle, PSNT/0.5 μg/hr IIK-7 and PSNT/0.5 μg IIK-7/1 μg 4-p/hr. To test the MT-2 dependence on IIK-7 activity, the animals were implanted with a single i.t catheter and injected MT-2 antagonist 4-Phenyl-2-propionamidotetralin (4-p) 20 mins prior to IIK-7 injection on day 7 after PSNT. The antinociceptive response was measured using a mechanical paw withdrawal threshold. Activation of microglial cells and the expression of NP-associated proteins in the spinal cord dorsal horn was assessed by immunofluorescence assay (IFA) and Western blotting (WB). Reactive oxygen species (ROS) scavenging ability of IIK-7 was evaluated by using bone marrow-derived macrophages (BMDM). Results Treatment with the MT-2 agonist IIK-7 significantly alleviated PSNT-induced mechanical allodynia and glial activation along with the inhibition of P44/42 MAPK, HMGB-1, STAT3, iNOS and casp-3 proteins. Conclusion IIK-7 attenuates NP through the suppression of glial activation and suppression of proteins involved in inflammation and apoptosis. MT-2 receptor agonists may establish a promising and unique therapeutic approach for the treatment of NP.

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“…Similar findings were detected by Mokhtar, et al 26 and Hussein, et al 27 on the adrenal gland. Also, melatonin plays a key role in peripheral nerve regeneration and development of the nervous system via its antioxidant activity 43 Our results revealed that melatonin administration induces hypertrophy and hyperplasia on sebaceous glands. Moreover, sebaceous gland activity depends on melatonin levels 44 .…”

Section: After Melatonin Treatmentmentioning

confidence: 53%

Melatonin induces a stimulatory action on the scrotal skin components of Soay ram in the non-breeding season

Mustafa

Abdel-Maksoud

Hassan

et al. 2020

Sci Rep

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Fifteen adult Soay rams were employed in this study to investigate the effect of melatonin on the scrotal skin using histological, histochemical, and morphometrical analysis. the results revealed that the melatonin treated group showed a significant increase in the thickness of the epidermis, the cross-sectional area of blood capillaries and nerve fibers compared with the control one. In addition, obvious hypertrophy and hyperplasia were detected in the sebaceous glands in association with a significant increase in the number and diameter of apocrine sweat glands with well-developed secretory activity. S100 protein and cytokeratin-19 strongly stained the basal cells of sebaceous glands in the melatonin treated group incomparable to the control group. Moreover, the nerve fibers were intensively immunoreacted for S100 and cytokeratin proteins in the melatonin treated group in contrast to the control one. A high number of telocytes (TCs) could be identified in the treated group around the nerve fibers and blood vessels in the dermis. The number of Langerhans cells showed a significant increase in the melatonin groups that were identified by MHC II and PGP 9.5 within the epidermal layer. Furthermore, a significant increase in the number of dendritic cells was identified in the melatonin group, which were distributed within the dermis, around hair follicles, sebaceous glands, and sweat glands and were strongly expressed PGP-9.5, MHC-II, VAMP, SNAP, keratin-5, and cytokeratin-19 immunoreactivity. Notably, Merkel cells showed a significant increase in the number in the melatonin group that could be stained against nestin, SNAP, and VAMP. On the other hand, the secretory granules in sweat glands were exhibited a strong positive reactivity for synaptophysin in melatonin group. The current study showed that the administration of melatonin induced a stimulatory effect on keratinocytes, non-keratinocytes, sebaceous and sweat glands, hair follicles, as well as the vascular, neuronal, and cellular constituents of the dermis. Melatonin is a Multitasking hormone that performs several functions to protect the body from different environmental conditions 1. Melatonin is not only produced by the Pineal gland but also synthesized by the ovary, testes, retina, Harderian gland and skin 2-4. Melatonin acts as an anti-inflammatory, antioxidant, anti-cancer agent, and exhibited strong anti-aging characters 5,6. The skin is considered the largest organ and covered 7-12% of the body and performs several vital functions 7. The skin is made of two distinguished parts, epidermis and dermis. The superficial one was the epidermis and formed mainly of keratinocytes and non-keratinocytes. Keratinocytes proliferation is regulated by melatonin 8. On the other hand, the non-keratinocytes including Langerhans cells that act as immune cells (dendritic cells of the epidermis), Merkel cells represent neuroendocrine cells of the epidermis and melanocytes, which are the main source of melanin that responsible for skin pigmentation and protection from ultr...

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Useful Effects of Melatonin in Peripheral Nerve Injury and Development of the Nervous System

Cited by 19 publications

References 43 publications

Melatonin Elicits Stimulatory Action on the Adrenal Gland of Soay Ram: Morphometrical, Immunohistochemical, and Ultrastructural Study

Melatonin Elicits Stimulatory Action on the Adrenal Gland of Soay Ram: Morphometrical, Immunohistochemical, and Ultrastructural Study

<p>Melatonin MT2 receptor agonist IIK-7 produces antinociception by modulation of ROS and suppression of spinal microglial activation in neuropathic pain rats</p>

Melatonin induces a stimulatory action on the scrotal skin components of Soay ram in the non-breeding season

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