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Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS.

Dahal S, Chitti SV, Nair MP, Saxena SK - Front Microbiol (2015)

Bottom Line: Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND).HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration.Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND.

View Article: PubMed Central - PubMed

Affiliation: CSIR-Centre for Cellular and Molecular Biology , Hyderabad, India.

ABSTRACT
Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to DA, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND). HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the blood brain barrier (BBB) in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies against HIV-1 infection in cocaine using HIV infected population.

No MeSH data available.


Related in: MedlinePlus

Prevalence of cocaine use in 2010 (UNODC). Source: UNODC estimates based on annual report questionnaire data and other official sources. The bound-aries and names shown and the designations used on this map do not imply official endorsement or acceptance by the United Nations. Final boundary between the Republic of Sudan and the Republic of South Sudan has not yet been determined. Dashed lines represent undermined bound-aries. Dotted line represents approximately the line of Control in Jammu and Kashmir agreed upon by India and Pakistan. The final status of Jammu and Kashmir has not yet been agreed upon by the parties. The final boundary between the Republic of Sudan and the Republic of South Sudan has not yet been determined.
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Figure 1: Prevalence of cocaine use in 2010 (UNODC). Source: UNODC estimates based on annual report questionnaire data and other official sources. The bound-aries and names shown and the designations used on this map do not imply official endorsement or acceptance by the United Nations. Final boundary between the Republic of Sudan and the Republic of South Sudan has not yet been determined. Dashed lines represent undermined bound-aries. Dotted line represents approximately the line of Control in Jammu and Kashmir agreed upon by India and Pakistan. The final status of Jammu and Kashmir has not yet been agreed upon by the parties. The final boundary between the Republic of Sudan and the Republic of South Sudan has not yet been determined.

Mentions: Acquired immunodeficiency syndrome (AIDS) is a condition caused by a virus called human immunodeficiency virus (HIV). AIDS is one of the most critically acclaimed endemic diseases, caused by lentivirus HIV-1 and HIV-2 which fatally impairs the immune system (Diwan et al., 2013). According to the 2013 World Health Organization report over 35 million people were living with HIV. HIV infection and progression of AIDS can be modulated by a number of cofactors, including drugs of abuse such as opioids, cocaine, cannabinoids, methamphetamine, alcohol, and others. According to the United Nations Office on Drugs and Crime (UNODC) (2012), about 230 million people (15–64 age group, Figure 1) are estimated to have used an illicit drug and estimated number of problem drug users in 2010 was between 15.5 million and 38.6 million and more over drug users continue to be a problem with drug dependence disorders such as the prevalence of HIV (20%), hepatitis C (46.7%) and hepatitis B (14.6%). Drug abuse and addiction have been linked with HIV/AIDS since the beginning of the epidemic (Reddy et al., 2012). Substance abuse is a major barrier in eradication of the HIV outbreak the reason is that, it serves as a powerful co-factor for transmission of virus, disease progression, and AIDS related mortality. Cocaine is one of the commonly abused drugs among HIV1 patients and it has been suggested to accelerate AIDS progression. However, the principal mechanism remains largely unknown, but in recent times it was been shown that cocaine alter the behavior and mood, causing feelings of euphoria by stimulating key pleasure centers within the brain. One of the most damaging effects of cocaine abuse is that it compromises judgment capacity leading to risky sexual behavior, thereby increasing chances of contracting HIV infection. Cocaine is the second most popular abused drug in United States (Zenón et al., 2014). It is a powerfully addictive CNS stimulating drug, which increases the level of neurotransmitter DA in the brain. It has been associated with known adverse effects on cardiac, gastrointestinal tract, cerebrovascular, and pulmonary systems. Cocaine abuse increases the incidence and severity of HIV neuropathology and associated cognitive deficits by enhancing viral replication. Enhancement of AIDS pathology includes multiple immunomodulatory effects of cocaine, its capability to dysregulate neurotoxins such as quinolinic acid (QUIN) and arachidonic acid (AA) metabolites and exacerbates neurotoxicity by co-operating with viral toxins (Yao et al., 2009; Nair and Samikkannu, 2012). Additionally cocaine is also familiar as an immunosuppressant and is capable of reducing number and distribution of immune cells, white blood cells and thymocytes. The battle between human and the HIV are on, with both of them rapidly improving their attacking and defense strategies (Saxena et al., 2002).


Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS.

Dahal S, Chitti SV, Nair MP, Saxena SK - Front Microbiol (2015)

Prevalence of cocaine use in 2010 (UNODC). Source: UNODC estimates based on annual report questionnaire data and other official sources. The bound-aries and names shown and the designations used on this map do not imply official endorsement or acceptance by the United Nations. Final boundary between the Republic of Sudan and the Republic of South Sudan has not yet been determined. Dashed lines represent undermined bound-aries. Dotted line represents approximately the line of Control in Jammu and Kashmir agreed upon by India and Pakistan. The final status of Jammu and Kashmir has not yet been agreed upon by the parties. The final boundary between the Republic of Sudan and the Republic of South Sudan has not yet been determined.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562305&req=5

Figure 1: Prevalence of cocaine use in 2010 (UNODC). Source: UNODC estimates based on annual report questionnaire data and other official sources. The bound-aries and names shown and the designations used on this map do not imply official endorsement or acceptance by the United Nations. Final boundary between the Republic of Sudan and the Republic of South Sudan has not yet been determined. Dashed lines represent undermined bound-aries. Dotted line represents approximately the line of Control in Jammu and Kashmir agreed upon by India and Pakistan. The final status of Jammu and Kashmir has not yet been agreed upon by the parties. The final boundary between the Republic of Sudan and the Republic of South Sudan has not yet been determined.
Mentions: Acquired immunodeficiency syndrome (AIDS) is a condition caused by a virus called human immunodeficiency virus (HIV). AIDS is one of the most critically acclaimed endemic diseases, caused by lentivirus HIV-1 and HIV-2 which fatally impairs the immune system (Diwan et al., 2013). According to the 2013 World Health Organization report over 35 million people were living with HIV. HIV infection and progression of AIDS can be modulated by a number of cofactors, including drugs of abuse such as opioids, cocaine, cannabinoids, methamphetamine, alcohol, and others. According to the United Nations Office on Drugs and Crime (UNODC) (2012), about 230 million people (15–64 age group, Figure 1) are estimated to have used an illicit drug and estimated number of problem drug users in 2010 was between 15.5 million and 38.6 million and more over drug users continue to be a problem with drug dependence disorders such as the prevalence of HIV (20%), hepatitis C (46.7%) and hepatitis B (14.6%). Drug abuse and addiction have been linked with HIV/AIDS since the beginning of the epidemic (Reddy et al., 2012). Substance abuse is a major barrier in eradication of the HIV outbreak the reason is that, it serves as a powerful co-factor for transmission of virus, disease progression, and AIDS related mortality. Cocaine is one of the commonly abused drugs among HIV1 patients and it has been suggested to accelerate AIDS progression. However, the principal mechanism remains largely unknown, but in recent times it was been shown that cocaine alter the behavior and mood, causing feelings of euphoria by stimulating key pleasure centers within the brain. One of the most damaging effects of cocaine abuse is that it compromises judgment capacity leading to risky sexual behavior, thereby increasing chances of contracting HIV infection. Cocaine is the second most popular abused drug in United States (Zenón et al., 2014). It is a powerfully addictive CNS stimulating drug, which increases the level of neurotransmitter DA in the brain. It has been associated with known adverse effects on cardiac, gastrointestinal tract, cerebrovascular, and pulmonary systems. Cocaine abuse increases the incidence and severity of HIV neuropathology and associated cognitive deficits by enhancing viral replication. Enhancement of AIDS pathology includes multiple immunomodulatory effects of cocaine, its capability to dysregulate neurotoxins such as quinolinic acid (QUIN) and arachidonic acid (AA) metabolites and exacerbates neurotoxicity by co-operating with viral toxins (Yao et al., 2009; Nair and Samikkannu, 2012). Additionally cocaine is also familiar as an immunosuppressant and is capable of reducing number and distribution of immune cells, white blood cells and thymocytes. The battle between human and the HIV are on, with both of them rapidly improving their attacking and defense strategies (Saxena et al., 2002).

Bottom Line: Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND).HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration.Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND.

View Article: PubMed Central - PubMed

Affiliation: CSIR-Centre for Cellular and Molecular Biology , Hyderabad, India.

ABSTRACT
Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to DA, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND). HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the blood brain barrier (BBB) in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies against HIV-1 infection in cocaine using HIV infected population.

No MeSH data available.


Related in: MedlinePlus