The peroxidative DNA damage and apoptosis in methamphetamine-treated rat brain

Abstract

In this study, we investigated methamphetamine (METH)- induced peroxidative DNA damage in various regions of the rat brain. We injected METH to rats following 2 protocols. For the single administration experiment (group I), 50 mg/kg (i. p.) of METH was administered to observe the acute influence of METH. For the repeated administration experiment (group II), 10 mg/kg/day (i. p.) of METH was injected for 5 days. Immunohistochemically, peroxidative damage DNA, 8-hydroxy-2'- deoxyguanosine (8-OH-dG) was observed, and in situ apoptosis was also observed. In group I, immunoreactivity of 8-OH-dG was only enhanced in neurons of the nucleus accumben of METH-treated rats. On in situ apoptosis detection, positive findings were also enhanced in all examined parts compared to those in the control, though there were no significant increases in 8-OH-dG-immunopositive neurons except in the nucleus accumben. In group II, the nucleus accumben also showed enhanced 8-OH-dG immunopositivity compared to that in the control. There was no significant difference in apoptosis between the control and METH groups. Based on our observations, it is considered that METH induces oxidative DNA damage in the brain, especially in the nucleus accumben. However, those DNA damage might be caused differently between acute and chronic administration.

Molecular, Behavioral, and Physiological Consequences of Methamphetamine Neurotoxicity: Implications for Treatment

“…METH toxicity in cell bodies is manifested by the presence of apoptosis and necrosis, astrocyte or microglia activation, as well as abnormal alterations in cell morphology or structure. METH-induced apoptosis of striatal GABA neurons and frontal cortical neurons depends on GLU and DA and involves mitochondrial dysfunction, endoplasmic reticulum stress, and calcium-influx activation of the calpain pathway (Deng et al, 2001;Jayanthi et al, 2004;Warren et al, 2005Warren et al, , 2007Tokunaga et al, 2008;Gold et al, 2009;Beauvais et al, 2011;Shiba et al, 2011). In the hippocampus, in addition to inducing apoptosis, which is often followed by blebbing of pyramidal neuron dendrites and death of pyramidal neurons and granular cells, METH inhibits neurogenesis and reduces hippocampal volume (Teuchert-Noodt et al, 2000;Deng et al, 2001;Thompson et al, 2004;Kuczenski et al, 2007;Mandyam et al, 2008;Kochman et al, 2009;Hori et al, 2010).…”

Preventive Effect of Baicalein on Methamphetamine-Induced Amnesia in the Passive Avoidance Test in Mice

“…Several lines of evidence showed that high doses or binge administration of methamphetamine increased oxidative stress, nitrotyrosine protein modification, lipid peroxidation, dopamine depletion and neuronal damage, while these effects can be attenuated by antioxidants such as deferoxamine, α-tocopherol and baicalein [8,9,10,11]. Furthermore, high doses or binge administration of methamphetamine also increased peroxidative DNA damage and apoptosis in rat brain [12]. …”

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

“…At high doses, METH causes the degeneration of dopaminergic (DAergic) and serotonergic nerve terminals, particularly in the striatum 3 . In neurons that are post-synaptic to striatal monoaminergic terminals, METH causes apoptosis, and cell death in some species 4 5 6 7 8 . In the hippocampus, METH dysregulates neurogenesis and induces apoptosis, which is often followed by the death of pyramidal neurons and granular cells 8 9 10 11 12 13 14 .…”