Methamphetamine induces <scp>DNA</scp> damage in specific regions of the female rat brain

Johnson, Z.; Venters, Jace; Guarraci, Fay A.; Zewail-Foote, Maha

doi:10.1111/1440-1681.12404

Cited by 17 publications

(7 citation statements)

References 50 publications

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“…High doses of METH induce DNA breaks 8 59 and apoptotic and necrotic death of SGZ and SVZ cells 9 46 60 . LINE-1 can “jump” into DNA at strand breaks 61 .…”

Section: Discussionmentioning

confidence: 99%

Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

Moszczynska

Flack

Qiu

et al. 2015

Sci Rep

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Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum.

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“…High doses of METH induce DNA breaks 8 59 and apoptotic and necrotic death of SGZ and SVZ cells 9 46 60 . LINE-1 can “jump” into DNA at strand breaks 61 .…”

Section: Discussionmentioning

confidence: 99%

Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

Moszczynska

Flack

Qiu

et al. 2015

Sci Rep

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“…A similar effect on DNA damage was observed after treatment of rats with the 5-HT2A agonist (±)DOI and MDMA. The oxidative damage of DNA was reported in brains of animals treated chronically with high doses of MDMA and methamphetamine (Frenzilli et al 2007 ; Johnson et al 2015 ). The mechanism of DNA oxidation by amphetamine derivatives is related to an oxidative stress and the formation of highly reactive free radicals.…”

Section: Discussionmentioning

confidence: 98%

Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats

et al. 2016

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5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, ‘foxy’) is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors. In this study, using microdialysis in freely moving rats, we examined the effect of 5-MeO-DIPT on dopamine (DA), serotonin (5-HT), and glutamate release in the rat striatum, nucleus accumbens, and frontal cortex. In search of a possible neurotoxic effect of 5-MeO-DIPT, we measured DA and 5-HT tissue content in the above rat brain regions and also determined the oxidative DNA damage with the comet assay. Moreover, we tested drug-elicited head-twitch response and a forepaw treading induced by 8-OH-DPAT. 5-MeO-DIPT at doses of 5, 10, and 20 mg/kg increased extracellular DA, 5-HT, and glutamate level but the differences in the potency were found between brain regions. 5-MeO-DIPT increased 5-HT and decreased 5-HIAA tissue content which seems to result from SERT inhibition. On the other hand, a decrease in DA, DOPAC, and HVA tissue contents suggests possible adaptive changes in DA turnover or damage of DA terminals by 5-MeO-DIPT. DNA single and double-strand breaks persisted up to 60 days after the treatment, indicating marked neurotoxicity of 5-MeO-DIPT. The induction of head-twitch response and potentiation of forepaw treading induced by 8-OH-DPAT indicate that hallucinogenic activity seems to be mediated through the stimulation of 5-HT2A and 5-HT1A receptors by 5-MeO-DIPT.

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“…All these molecules share structural and pharmaceutical similarities with amphetamine derivatives which are also considered to be risk factors for PAH [ 108 , 198 , 199 , 200 , 201 ]. Fenfluramines, amphetamines and derivatives had been reported to induce systemic DNA damages through oxidative stress [ 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 ]. Fenfluramine derivatives are also substrates for the serotonin transporter and potent serotonin uptake inhibitors [ 201 , 212 ].…”

Section: Dna Damage In Pulmonary Arterial Hypertensionmentioning

confidence: 99%

DNA Damage and Pulmonary Hypertension

Ranchoux

Meloche

Paulin

et al. 2016

IJMS

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Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis.

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Methamphetamine induces DNA damage in specific regions of the female rat brain

Cited by 17 publications

References 50 publications

Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats

DNA Damage and Pulmonary Hypertension

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