Peripheral ammonia and blood brain barrier structure and function after methamphetamine

Northrop, Nicole A.; Halpin, Laura E.; Yamamoto, Bryan K.

doi:10.1016/j.neuropharm.2016.03.018

Cited by 32 publications

(27 citation statements)

References 58 publications

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“…HIV-1 proteins also stimulate matrix metalloproteinase (MMP) and proteasome activity, which can increase the degradation of barrier proteins that impact barrier continuity [ 67 , 68 ]. Methamphetamine has pro-inflammatory effects in brain [ 69 ] and detrimental effects on blood-brain barrier integrity via activation of MMP-9 in rodents [ 70 , 71 ]. It is plausible that the capacity of methamphetamine to alter intestinal tight junctions may also involve the pro-inflammatory cascades or increased MMP pathways.…”

Section: Discussionmentioning

confidence: 99%

Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats

et al. 2018

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The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.

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Section: Discussionmentioning

confidence: 99%

Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats

et al. 2018

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“…METH induces peripheral kidney and liver damage that leads to toxic ammonia levels in the blood and subsequently, the brain. Ammonia that is not cleared by the liver as normal accumulates and causes oxidative damage of endothelial cells, activation of matrix metalloproteases (MMPs) and neuro-inflammation via microglia and astrocyte activation, leading to BBB disruption (28)(29)(30) (Fig. 1).…”

Section: Meth and The Blood-brain Barriermentioning

confidence: 99%

Methamphetamine: Effects on the brain, gut and immune system

Prakash

Tangalakis

Antonipillai

et al. 2017

Pharmacological Research

143

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Methamphetamine (METH) is a powerful central nervous system stimulant which elevates mood, alertness, energy levels and concentration in the short-term. However, chronic use and/or at higher doses METH use often results in psychosis, depression, delusions and violent behavior. METH was formerly used to treat conditions such as obesity and attention deficit hyperactivity disorder, but now is primarily used recreationally. Its addictive nature has led to METH abuse becoming a global problem. At a cellular level, METH exerts a myriad of effects on the central and peripheral nervous systems, immune system and the gastrointestinal system. Here we present how these effects might be linked and their potential contribution to the pathogenesis of neuropsychiatric disorders. In the long term, this pathway could be targeted therapeutically to protect people from the ill effects of METH use. This model of METH use may also provide insight into how gut, nervous and immune systems might break down in other conditions that may also benefit from therapeutic intervention.

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“…; Northrop et al . )]. Furthermore, neuroinflammation is associated with a variety of neurotoxicant exposures, which induce damage to the CNS (Thomas et al .…”

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confidence: 99%

Corticosterone and exogenous glucose alter blood glucose levels, neurotoxicity, and vascular toxicity produced by methamphetamine

Bowyer

Tranter

Sarkar

et al. 2017

Journal of Neurochemistry

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Our previous studies have raised the possibility that altered blood glucose levels may influence and/or be predictive of methamphetamine (METH) neurotoxicity. This study evaluated the effects of exogenous glucose and corticosterone (CORT) pretreatment alone or in combination with METH on blood glucose levels and the neural and vascular toxicity produced. METH exposure consisted of four sequential injections of 5, 7.5, 10, and 10 mg/kg (2h between injections) D-METH. The three groups given METH in combination with saline, glucose (METH+Glucose), or CORT (METH+CORT) had significantly higher glucose levels compared to the corresponding treatment groups without METH except at 3 h after the last injection. At this last time point, the METH and METH+Glucose groups had lower levels than the non-METH groups, while the METH+CORT group did not. CORT alone or glucose alone did not significantly increase blood glucose. Mortality rates for the METH+CORT (40%) and METH+Glucose (44%) groups were substantially higher than the METH (< 10%) group. Additionally, METH+CORT significantly increased neurodegeneration above all other treatments (≈ 2.5-fold in the parietal cortex). Thus, maintaining elevated levels of glucose during METH exposure increases lethality and may exacerbate neurodegeneration. Neuroinflammation, specifically microglial activation, was associated with degenerating neurons in the parietal cortex and thalamus after METH exposure. The activated microglia in the parietal cortex were surrounding vasculature in most cases and the extent of microglial activation was exacerbated by CORT pretreatment. Our findings implicate elevated blood levels of glucose and hyperthermia in METH-induced neurotoxicity, neurovascular damage, and lethality, and that acute elevation of CORT exacerbates both neurotoxicity and neuroinflammation.

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Peripheral ammonia and blood brain barrier structure and function after methamphetamine

Cited by 32 publications

References 58 publications

Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats

Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats

Methamphetamine: Effects on the brain, gut and immune system

Corticosterone and exogenous glucose alter blood glucose levels, neurotoxicity, and vascular toxicity produced by methamphetamine

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