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Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies.

ABSTRACT: Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and substance abuse are often comorbid, we discuss the potential role of EVs in the intersection of substance abuse and HIV. Taken together, the studies presented in this comprehensive review shed light on the potential role of EVs in the exacerbation of substance use and HIV. As a subject of growing interest, EVs may continue to provide information about mechanisms and pathogenesis in substance use disorders and CNS pathologies, perhaps allowing for exploration into potential therapeutic options.

SUBMITTER: Odegaard KE

PROVIDER: S-EPMC7554956 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies.

Odegaard Katherine E KE Chand Subhash S Wheeler Sydney S Tiwari Sneham S Flores Adrian A Hernandez Jordan J Savine Mason M Gowen Austin A Pendyala Gurudutt G Yelamanchili Sowmya V SV

International journal of molecular sciences 20200915 18

Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the f ...[more]

PMID: 32942668

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Project description:Extracellular vesicles are released by all cell types and contain proteins, microRNAs, mRNAs, and other bioactive molecules. Extracellular vesicles play an important role in intercellular communication and in the modulation of the immune system and neuroinflammation. The cargo of extracellular vesicles (e.g., proteins and microRNAs) is altered in pathological situations. Extracellular vesicles contribute to the pathogenesis of many pathologies associated with sustained inflammation and neuroinflammation, including cancer, diabetes, hyperammonemia and hepatic encephalopathy, and other neurological and neurodegenerative diseases. Extracellular vesicles may cross the blood-brain barrier and transfer pathological signals from the periphery to the brain. This contributes to inducing neuroinflammation and cognitive and motor impairment in hyperammonemia and hepatic encephalopathy and in neurodegenerative diseases. The mechanisms involved are beginning to be understood. For example, increased tumor necrosis factor α in extracellular vesicles from plasma of hyperammonemic rats induces neuroinflammation and motor impairment when injected into normal rats. Identifying the mechanisms by which extracellular vesicles contribute to the pathogenesis of these diseases will help to develop new treatments and diagnostic tools for their easy and early detection. In contrast, extracellular vesicles from mesenchymal stem cells have therapeutic utility in many of the above pathologies, by reducing inflammation and neuroinflammation and improving cognitive and motor function. These extracellular vesicles recapitulate the beneficial effects of mesenchymal stem cells and have advantages as therapeutic tools: they are less immunogenic, may not differentiate to malignant cells, cross the blood-brain barrier, and may reach more easily target organs. Extracellular vesicles from mesenchymal stem cells have beneficial effects in models of ischemic brain injury, Alzheimer's and Parkinson's diseases, hyperammonemia, and hepatic encephalopathy. Extracellular vesicles from mesenchymal stem cells modulate the immune system, promoting the shift from a pro-inflammatory to an anti-inflammatory state. For example, extracellular vesicles from mesenchymal stem cells modulate the Th17/Treg balance, promoting the anti-inflammatory Treg. Extracellular vesicles from mesenchymal stem cells may also act directly in the brain to modulate microglia activation, promoting a shift from a pro-inflammatory to an anti-inflammatory state. This reduces neuroinflammation and improves cognitive and motor function. Two main components of extracellular vesicles from mesenchymal stem cells which contribute to these beneficial effects are transforming growth factor-β and miR-124. Identifying the mechanisms by which extracellular vesicles from mesenchymal stem cells induce the beneficial effects and the main molecules (e.g., proteins and mRNAs) involved may help to improve their therapeutic utility. The aims of this review are to summarize the knowledge of the pathological effects of extracellular vesicles in different pathologies, the therapeutic potential of extracellular vesicles from mesenchymal stem cells to recover cognitive and motor function and the molecular mechanisms for these beneficial effects on neurological function.

Project description:BackgroundTraditional healers are acceptable and highly accessible health practitioners throughout sub-Saharan Africa. Patients in South Africa often seek concurrent traditional and allopathic treatment leading to medical pluralism.Methods & findingsWe studied the cause of five traditional illnesses known locally as "Mavabyi ya nhloko" (sickness of the head), by conducting 27 in-depth interviews and 133 surveys with a randomly selected sample of traditional healers living and working in rural, northeastern South Africa. These interviews were carried out to identify treatment practices of mental, neurological, and substance abuse (MNS) disorders. Participating healers were primarily female (77%), older in age (median: 58.0 years; interquartile range [IQR]: 50-67), had very little formal education (median: 3.7 years; IQR: 3.2-4.2), and had practiced traditional medicine for many years (median: 17 years; IQR: 9.5-30). Healers reported having the ability to successfully treat: seizure disorders (47%), patients who have lost touch with reality (47%), paralysis on one side of the body (59%), and substance abuse (21%). Female healers reported a lower odds of treating seizure disorders (Odds Ratio (OR):0.47), patients who had lost touch with reality (OR:0.26; p-value<0.05), paralysis of one side of the body (OR:0.36), and substance abuse (OR:0.36) versus males. Each additional year of education received was found to be associated with lower odds, ranging from 0.13-0.27, of treating these symptoms. Each additional patient seen by healers in the past week was associated with roughly 1.10 higher odds of treating seizure disorders, patients who have lost touch with reality, paralysis of one side of the body, and substance abuse. Healers charged a median of 500 South African Rand (~US$35) to treat substance abuse, 1000 Rand (~US$70) for seizure disorders or paralysis of one side of the body, and 1500 Rand (~US$105) for patients who have lost touch with reality.ConclusionsWhile not all healers elect to treat MNS disorders, many continue to do so, delaying allopathic health services to acutely ill patients.

Dataset Information

Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies.

Publications

Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies.

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