No abstract

No abstract

Tacrine is a small organic compound that was discovered to mimic the functions of the neural cell adhesion molecule L1 by promoting the cognate functions of L1 in vitro, such as neuronal survival, neuronal migration, neurite outgrowth, and myelination. Based on studies indicating that L1 enhances functional recovery in different central and peripheral nervous system disease paradigms of rodents, it deemed interesting to investigate the beneficial role of tacrine in the attractive zebrafish animal model, by evaluating functional recovery after spinal cord injury. To this aim, larval and adult zebrafish were exposed to tacrine treatment after spinal cord injury and monitored for locomotor recovery and axonal regrowth. Tacrine promoted the rapid recovery of locomotor activities in both larval and adult zebrafish, enhanced regrowth of severed axons and myelination, and reduced astrogliosis in the spinal cords. Tacrine treatment upregulated the expression of L1.1 (a homolog of the mammalian recognition molecule L1) and enhanced the L1.1-mediated intracellular signaling cascades in the injured spinal cords. These observations lead to the hope that, in combination with other therapeutic approaches, this old drug may become a useful reagent to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.

No abstract

Besides several endogenous elements, exogenous factors, including exposure to pesticides, have been recognized as putative factors contributing to the onset and development of neurodegenerative diseases, including Parkinson's disease (PD). Considering the availability, success rate, and limitations associated with the current arsenals to fight PD, there is an unmet need for novel therapeutic interventions. Therefore, based on the previously reported beneficial functions of the L1 cell adhesion molecule, we hypothesized that L1 mimetic compounds may serve to neutralize neurotoxicity triggered by the pesticide paraquat (PQ). In this study, we attempt to use PQ for inducing PD-like pathology and the L1 mimetic compounds phenelzine sulfate (PS) and tacrine (TC) as potential candidates for the amelioration of PD symptoms using zebrafish as a model system. Administration of PQ together with the L1 mimetic compounds PS or TC (250 nM) improved survival of zebrafish larvae, protected them from locomotor deficits, and increased their sensorimotor reflexes. Moreover, application of PQ together with PS (500 nM) or TC (1000 nM) in adult zebrafish counteracted PQ-induced toxicity, maintaining normal locomotor functions and spatial memory in an open field and T-maze task, respectively. Both L1 mimetic compounds prevented reduction in tyrosine hydroxylase and dopamine levels, reduced reactive oxygen species (ROS) generation, protected against impairment of mitochondrial viability, improved the antioxidant enzyme system, and prevented a decrease in ATP levels. Altogether, our findings highlight the beneficial functions of the agonistic L1 mimetics PS and TC by improving several vital cell functions against PQ-triggered neurotoxicity.

These results show the neuroprotective abilities of resveratrol against prenatal-stress-induced oxidative damage in neonatal rat brain.

AIm: Prenatal stress is known to adversely affect the fetal brain development and also neuronal loss. The mechanism(s) associated with prenatal stress induced developmental neurotoxicity remains obscure. Few studies point to the glutathione (GSH) antioxidant system which is an important molecular target for this toxicant. Hence the present study investigates the effect of prenatal stress on glutathione system in neonatal rat brain. mATeRIAL and meTHods: Three to four months old pregnant Wistar rats were subjected to restraint stress during early or late gestational period. The offspring were sacrificed on 40th day and their brain homogenate was subjected to antioxidant studies. The serum corticosterone and adrenal ascorbic acid levels were also estimated from offspring. ResuLTs:The prenatal stress has resulted in an increase in the serum corticosterone and reduced adrenal ascorbic acid levels in neonatal pups. Prenatal stress during early or late gestation life showed reduced glutathione, glutathione reductase (GSSG-Rd) and superoxide dismutase (SOD) activity in offspring brain homogenate.CoNCLusIoN: These data suggest that stress during early or late gestation period affect glutathione system in developing neonatal rat brain, which is associated with elevated serum corticosterone and reduced adrenal ascorbic acid levels.KeywoRds: Prenatal stress, Glutathione, Glutathione reductase, Superoxide dismutase, Antioxidant enzymes ÖZ AmAÇ: Prenatal stresin fetal beyin gelişimi ve ayrıca nöron kaybını olumsuz şekilde etkilediği bilinmektedir. Prenatal stres tarafından indüklenen gelişimsel nörotoksisiteyle ilişkili mekanizma(lar) halen bilinmemektedir. Birkaç çalışma bu toksik madde için önemli bir moleküler hedef olan glutatyon (GSH) antioksidan sistemine işaret etmektedir. Bu nedenle bu çalışma neonatal sıçan beyninde prenatal stresin glutatyon sistemi üzerine etkisini incelemektedir. yÖNTem ve GeReÇLeR: Üç ila dört aylık hamile Wistar sıçanları erken veya geç gestasyonel dönemde zaptetme stresine maruz bırakıldı. Yavrular 40. günde sakrifiye edildi ve beyin homojenatları antioksidan çalışmalara tabi tutuldu. Ayrıca yavrularda serum kortikosteron ve adrenal askorbik asit düzeyleri saptandı.BuLGuLAR: Prenatal stres neonatal sıçanlarda artmış serum kortikosteron ve azalmış adrenal askorbik asit düzeylerine neden oldu. Erken veya geç gestasyonda prenatal stres, yavruların beyin homojenatında azalmış glutatyon, glutatyon redüktaz (GSSG-Rd) ve süperoksit dismutaz (SOD) aktivitesine neden oldu. soNuÇ: Bu veriler erken veya geç gestasyon döneminde stresin gelişen neonatal sıçan beyninde glutatyon sistemini etkilediği ve sonuçta artmış serum kortikosteron ve azalmış adrenal askorbik asit düzeyleriyle ilişkili olduğunu düşündürmektedir.

This study provides new insights into the role of phenelzine in L1-mediated neural functions and modulation of inflammation. The combined results raise hopes that phenelzine may develop into a therapeutic agent for nervous system injuries.