The Effect of Intrauterine Acute Ethanol Exposure on Developing Sciatic Nerves and Their Myelination: A Stereological Study

Abstract

Ethanol (ETH) delays myelination in the sciatic nerve of rat following fetal exposure. It has been suggested that melatonin (MLT), a naturally occurring indole, may be a potential protective agent for ETH toxicity, possibly due to its protective effects against free radical damage in experimental models. However, the precise mechanism of MLT protection in the development of the rat sciatic nerves and their myelination is unclear. In this study, the effect of ETH, MLT and ETH+MLT on the myelin thickness, axon number and axonal area of rat sciatic nerve were investigated. Pregnant rats were injected with either 25% ETH (dosage 2g/kg body weight), 25% ETH plus MLT (dosage 2g/kg and 10 mg/kg, respectively), MLT (dosage 10 mg/kg) or physiological saline (dosage 1 ml/kg) at 7, 15 and 20 days post-conception (first, second and third trimesters, respectively). At postnatal day 14, sciatic nerves of offspring were dissected out and processed for stereological analyses. Our results demonstrated that the myelin thickness was increased by exogenous MLT, and decreased by acute ETH, during first and second trimesters. It was found that MLT was protective to developing myelin thickness following fetal exposure during the first trimester, whereas it was toxic to myelin thickness during the third trimester. The presented study is the first stereological study indicating that exogenous MLT has a toxic effect on the myelin thickness of rat sciatic nerves during the third trimester. Based on our findings, we suggested that exogenous MLT, given during the third trimester as an antioxidant agent, as well as acute ETH, given in the first and second trimesters, may alter the normal development of sciatic nerve myelination. Journal of Experimental and Clinical Medicine Deneysel ve Klinik Tıp Dergisi 36A k t a ş e t a l .

Melatonin promotes Schwann cell dedifferentiation and proliferation through the Ras/Raf/ERK and MAPK pathways, and glial cell‑derived neurotrophic factor expression

“…The findings from a previous study suggested that melatonin could suppress collagen scar formation after PNI ( 23 ). Melatonin also increased the number of axons and the thickness of the myelin sheath after PNI ( 4 ). Stavisky et al ( 25 ) demonstrated that melatonin enhanced the repair of sciatic nerve crush injuries in rats.…”

“…After an injury, peripheral axons activate the intrinsic growth capacity in the neuronal cell body and promote axonal regeneration ( 2 ). Previous studies have suggested that Schwann cells are important in the regeneration of peripheral axons and functional recovery ( 3 , 4 ). After the events of a PNI, mature Schwann cells dedifferentiate into progenitor-like Schwann cells, known as Schwann cell precursors, promote myelin debris clearance and tubular reconstruction, and also form a cellular bridge spanning the gap between ends of damaged nerves ( 5 , 6 ).…”

Effect of Melatonin on Peripheral Nerve Damage Resulting from Tibial Defect in Rats

“…Their results showed that the therapeutic use of MLT could be a promising strategy to counteract PNI-induced neuronal disability. It has been defined that MLT has positive effects on axon number and myelin sheath thickness by preventing collagen deposition and neuroma formation after traumatic events in peripheral nerves (Aktas¸ et al, 2009). Degeneration of the endoneural and perineural sheath, hyperplasia of schwannocytus, and degeneration of axonal structures were observed in the defect group.…”

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“…41 Data from the literature, together with our studies using a different kind of experimental injury model, showed that MLT has positive effects on the number of axons and the thickness of the myelin sheath by inhibiting collagen accumulation and neuroma formation following traumatic events to peripheral nerves, and on the myelination of a developing peripheral nerve after intrauterine ethanol exposure. 42 As a result, the minimal dose of MLT necessary for an effect on peripheral nerve regeneration can be ascertained. Ulugol et al determined the effects of intracerebroventricular (i.c.v.)…”