Impact of methamphetamine on infection and immunity

Salamanca, Sandra Martin; Sorrentino, Edra E.; Nosanchuk, Joshua D.; Martinez, Luis R.

doi:10.3389/fnins.2014.00445

Cited by 93 publications

(90 citation statements)

References 160 publications

(222 reference statements)

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“…Since HIV-positive individuals on therapeutic treatment are frequently users of recreational drugs, such as METH, we next investigated the effect of this psychostimulant combined with different ARV compounds on neuronal-glial cultures after 24 h (referred to here as short-term exposure) and 7 days (referred to here as long-term exposure) of treatment. A concentration of 100 M METH was chosen for our experiments, based on previous studies suggesting that a concentration in this range can be reached in the brain during METH binges (56,57). Neuronal damage was assessed by quantifying the immunofluorescence signals of MAP-2-positive neurons and synaptophysinstained presynaptic terminals (Fig.…”

Section: Short-term Exposure To Arv Drugs Does Not Alter Dendritic Mamentioning

confidence: 99%

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Sánchez

Varano

Rozieres

et al. 2016

Antimicrob Agents Chemother

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b HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART).Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.

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Section: Short-term Exposure To Arv Drugs Does Not Alter Dendritic Mamentioning

confidence: 99%

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Sánchez

Varano

Rozieres

et al. 2016

Antimicrob Agents Chemother

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“…A variety of substances of abuse, including methamphetamine (Meth), opiates, cocaine, and alcohol, are known to induce immune suppression and enhance HIV replication (Martin-Thormeyer and Paul 2009; Salamanca et al 2014). Accumulating evidence from neuropsychological, neuroimaging, and neuropathological studies suggests that substance abuse heightens the adverse effects of HIV infection on the CNS (Anthony et al 2008; Rosenbloom et al 2010; Fama et al 2011; Pfefferbaum et al 2012; Zahr et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models

Soontornniyomkij

Kesby

Morgan

et al. 2016

J Neuroimmune Pharmacol

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Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value.

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“…METH abuse can alter biological processes and immune functions necessary for host defense [33, 34]. Antigen presenting cells play major roles as sentinels for first line alerts or as mediators that shape the adaptive immune response.…”

Section: Discussionmentioning

confidence: 99%

Capsular specific IgM enhances complement-mediated phagocytosis and killing of Cryptococcus neoformans by methamphetamine-treated J774.16 macrophage-like cells

Aslanyan

Ekhar

DeLeon-Rodriguez

et al. 2017

International Immunopharmacology

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Methamphetamine (METH) is a powerful and highly addictive stimulant that affects the central nervous system of users in the United States and worldwide, and its consumption is associated to the acquisition of HIV and AIDS-related infections. METH enhances cryptococcosis in mice, an opportunistic infection caused by the encapsulated fungus Cryptococcus neoformans. Due to its ability to survive within macrophages, C. neoformans is an ideal model to study pathogen-macrophage interactions. METH abrogates normal macrophage function, which might contribute to the higher rate and more rapid progression of infections in drug abusers. Hence, we investigated the role of complement and specific IgM to C. neoformans capsular polysaccharide on the function of J774.16 macrophage-like cells after exposure to METH. We found that complement and IgM significantly promotes complement-mediated phagocytosis of C. neoformans by J774.16 cells in comparison to co-incubation with complement alone. IgM enhances the expression of complement receptor 3 on the surface macrophages treated with the drug. Also, IgM-increased macrophage phagocytosis of C. neoformans may be associated with upregulation of GTPase-RhoA, a key regulator of the actin polymerization signaling cascade. Fungal cells incubated with complement and IgM in the presence of METH demonstrated higher number of cells per aggregate, a possible explanation for their enhanced ingestion by phagocytes. IgM increased killing of yeast cells by macrophages by inhibiting the alkalization of the phagosome and stimulating the intracellular production of nitric oxide. Together, our findings suggest that IgM stimulates the effector functions of macrophages against opportunistic pathogens in the setting of drug abuse.

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Impact of methamphetamine on infection and immunity

Cited by 93 publications

References 160 publications

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models

Capsular specific IgM enhances complement-mediated phagocytosis and killing of Cryptococcus neoformans by methamphetamine-treated J774.16 macrophage-like cells

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