Search

3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate. [ABSTRACT FROM AUTHOR]

Serotonin (5-HT) plays a crucial role in modulating the afferent fiber discharge rate in the inferior colliculus, auditory cortex, and other nuclei of the ascending auditory system. Resveratrol, a natural polyphenol phytoalexin, can inhibit serotonin transporters (SERT) to increase synaptic 5-HT levels. In this study, we investigated the effects of resveratrol on noise-induced damage in the serotonergic system. Male Sprague-Dawley rats were anaesthetized and exposed to an 8-kHz tone at 116 dB for 3.5 h. Resveratrol (30 mg/kg, intraperitoneal injection [IP]) and citalopram (20 mg/kg, IP), a specific SERT inhibitor used as a positive control, were administered once a day for four consecutive days, with the first treatment occurring 2 days before noise exposure. Auditory brainstem response testing and positron emission tomography (PET) with N , N -dimethyl-2-(2-amino-4-[ 18 F]fluorophenylthio)benzylamine (4-[ 18 F]-ADAM, a specific radioligand for SERT) were used to evaluate functionality of the auditory system and integrity of the serotonergic system, respectively, before and after noise exposure. Finally, immunohistochemistry was performed 1 day after the last PET scan. Our results indicate that noise-induced serotonergic fiber loss occurred in multiple brain regions including the midbrain, thalamus, hypothalamus, striatum, auditory cortex, and frontal cortex. This noise-induced damage to the serotonergic system was ameliorated in response to treatment with resveratrol and citalopram. However, noise exposure increased the hearing threshold in the rats regardless of drug treatment status. We conclude that resveratrol has protective effects against noise-induced loss of SERT.

3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [ 123 I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [ 123 I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [ 123 I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.

Purpose: To investigate the protective effects of glucosamine (GlcN) using oxidative stress and rat models of ischemia-reperfusion (I/R) injury and to determine the antiapoptotic and anti-inflammatory mechanisms of GlcN treatment., Methods: We determined the effects of GlcN and the levels of O-linked N-acetylglucosamine (O-GlcNAc) in in vitro retinal ganglion cells (RGCs) treated with or without H₂O₂. The survival and apoptosis rates of RGCs were compared after the addition of GlcN, glucose, or O-(2-acetamido-2-deoxy-Dglucopyranosylidene) amino-N-phenylcarbamate (PUGNAc). Retinal I/R injury was induced in Sprague-Dawley rats by elevating the IOP to 110 mm Hg for 60 minutes. An intraperitoneal injection of GlcN (1000 mg/kg) or normal saline was administered in the different groups, including a control group, a GlcN group, an I/R group, a GlcN+I/R group (1000 mg/kg GlcN 24 hours before I/R injury), and an I/R+GlcN group (7-day period of 1000 mg/kg GlcN 24 hours after I/R injury). The rats were killed 7 days after the I/R injury, and the retinas were collected from each rat for thickness measurements. Quantitative analysis of RGC survival was further determined using labeling with FluoroGold., Results: The GlcN increased levels of O-GlcNAc in a dose-dependent manner in the RGCs treated with or without H₂O₂. The GlcN resulted in increased cell survival and reduced apoptosis in the RGCs under oxidative stress conditions. In the rat model of I/R injury, GlcN significantly protected against I/R-induced retinal thinning and suppressed the I/R-induced reductions in a- and b-wave amplitudes of the ERG. In terms of RGC survival, significant incremental density of RGCs was found in the I/R+GlcN group compared with the I/R group. Notably, the use of GlcN in the rat retina decreased apoptosis and the formation of reactive oxygen species (ROS) after I/R injury. We also found that mitogen-activated protein kinase signal pathways played a critical role in the GlcN-mediated attenuation of ROS-induced damage in vitro and I/R injury in vivo., Conclusions: Glucosamine treatment provides multiple levels of retinal protection, including antiapoptotic, anti-inflammatory, and antioxidative benefits. More research on the role of GlcN as a potential agent for the prevention and treatment of glaucoma is warranted., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)