Different Roles of Beclin1 in the Interaction Between Glia and Neurons after Exposure to Morphine and the HIV- Trans-Activator of Transcription (Tat) Protein

Lapierre, Jessica; Karuppan, Mohan Kumar Muthu; Perry, Marissa; Rodriguez, Myosotys; El‐Hage, Nazira

doi:10.1007/s11481-021-10017-4

Cited by 7 publications

(9 citation statements)

References 111 publications

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“…The rationale for using motor behavioral assessments is based on the neurocognitive impairment seen in HIV, which includes a progressive loss/weakness in limbs and motor skills [ 6 , 54 ]. In a previous report by us [ 30 ], we used similar mouse models exposed to the HIV Tat protein via intracranial injection for a short period of time. We reported an increase in the performance of the horizontal bar in Tat-exposed Becn1 +/− when compared to Tat-exposed control animals [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…In a previous report by us [ 30 ], we used similar mouse models exposed to the HIV Tat protein via intracranial injection for a short period of time. We reported an increase in the performance of the horizontal bar in Tat-exposed Becn1 +/− when compared to Tat-exposed control animals [ 30 ]. Here, our findings showed a decrease in the performance of the horizontal bar and rotarod in mice infected with EcoHIV, irrespective of the strain.…”

Section: Discussionmentioning

confidence: 99%

“…The maximum strength of the grip prior to grip release was recorded. After the gs test, each animal was placed on the hb test, consisting of a 2 mm and a 4 mm bar, to measure the strength of the forelimbs [ 28 , 29 , 30 ].…”

Section: Methodsmentioning

confidence: 99%

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Implication of the Autophagy-Related Protein Beclin1 in the Regulation of EcoHIV Replication and Inflammatory Responses

Rodriguez,

Owens,

Perry

et al. 2023

Viruses

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The protein Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) plays an important role in the initiation and the normal process of autophagy in cells. Moreover, we and others have shown that Beclin1 plays an important role in viral replication and the innate immune signaling pathways. We previously used the cationic polymer polyethyleneimine (PEI) conjugated to mannose (Man) as a non-viral tool for the delivery of a small interfering (si) Beclin1-PEI-Man nanoplex, which specifically targets mannose receptor-expressing glia (microglia and astrocytes) in the brain when administered intranasally to conventional mice. To expand our previous reports, first we used C57BL/6J mice infected with EcoHIV and exposed them to combined antiretroviral therapy (cART). We show that EcoHIV enters the mouse brain, while intranasal delivery of the nanocomplex significantly reduces the secretion of HIV-induced inflammatory molecules and downregulates the expression of the transcription factor nuclear factor (NF)-kB. Since a spectrum of neurocognitive and motor problems can develop in people living with HIV (PLWH) despite suppressive antiretroviral therapy, we subsequently measured the role of Beclin1 in locomotor activities using EcoHIV-infected BECN1 knockout mice exposed to cART. Viral replication and cytokine secretion were reduced in the postmortem brains recovered from EcoHIV-infected Becn1+/− mice when compared to EcoHIV-infected Becn1+/+ mice, although the impairment in locomotor activities based on muscle strength were comparable. This further highlights the importance of Beclin1 in the regulation of HIV replication and in viral-induced cytokine secretion but not in HIV-induced locomotor impairments. Moreover, the cause of HIV-induced locomotor impairments remains speculative, as we show that this may not be entirely due to viral load and/or HIV-induced inflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Implication of the Autophagy-Related Protein Beclin1 in the Regulation of EcoHIV Replication and Inflammatory Responses

Rodriguez,

Owens,

Perry

et al. 2023

Viruses

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“…Aging leads to neuronal alterations–such as changes in neuronal morphology, neuronal damage, and dysregulation of neuronal signaling pathways–which also contribute to neuroinflammation and aging. Emerging studies have demonstrated that neuronal autophagy plays an essential role in neuroinflammation, aging, and HIV-1 dementia [ 167 , 168 , 169 ]. Atg7 is an E1-like enzyme required for autophagosome biogenesis [ 170 ].…”

Section: Neurons Autophagy and Agingmentioning

confidence: 99%

“…Studies also demonstrated that in these patients, dysregulation of neuronal autophagy was associated with HIV-1 dementia and encephalitis [ 167 , 168 ]. As the brain is a target of various drugs of abuse, including morphine, which results in various cellular signaling alterations [ 177 , 178 ], it is not surprising that increased neuronal loss was found in HIV-1 Tat and morphine-administered Becn1 +/+ mice but not in Becn1 +/− mice [ 169 , 179 ]. These findings also suggest a role of autophagy in HIV-1 Tat and morphine-mediated neuronal damage.…”

Section: Neurons Autophagy and Agingmentioning

confidence: 99%

Role of Autophagy in HIV-1 and Drug Abuse-Mediated Neuroinflammaging

Sil

Thangaraj

Oladapo

et al. 2022

Viruses

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Chronic low-grade inflammation remains an essential feature of HIV-1 infection under combined antiretroviral therapy (cART) and contributes to the accelerated cognitive defects and aging in HIV-1 infected populations, indicating cART limitations in suppressing viremia. Interestingly, ~50% of the HIV-1 infected population on cART that develops cognitive defects is complicated by drug abuse, involving the activation of cells in the central nervous system (CNS) and neurotoxin release, altogether leading to neuroinflammation. Neuroinflammation is the hallmark feature of many neurodegenerative disorders, including HIV-1-associated neurocognitive disorders (HAND). Impaired autophagy has been identified as one of the underlying mechanisms of HAND in treated HIV-1-infected people that also abuse drugs. Several lines of evidence suggest that autophagy regulates CNS cells’ responses and maintains cellular hemostasis. The impairment of autophagy is associated with low-grade chronic inflammation and immune senescence, a known characteristic of pathological aging. Therefore, autophagy impairment due to CNS cells, such as neurons, microglia, astrocytes, and pericytes exposure to HIV-1/HIV-1 proteins, cART, and drug abuse could have combined toxicity, resulting in increased neuroinflammation, which ultimately leads to accelerated aging, referred to as neuroinflammaging. In this review, we focus on the potential role of autophagy in the mechanism of neuroinflammaging in the context of HIV-1 and drug abuse.

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Methamphetamine and HIV-1 Tat Protein Synergistically Induce Endoplasmic Reticulum Stress to Promote TRIM13-Mediated Neuronal Autophagy

Wang,

Yang,

Huang

et al. 2024

Mol Neurobiol

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Different Roles of Beclin1 in the Interaction Between Glia and Neurons after Exposure to Morphine and the HIV- Trans-Activator of Transcription (Tat) Protein

Cited by 7 publications

References 111 publications

Implication of the Autophagy-Related Protein Beclin1 in the Regulation of EcoHIV Replication and Inflammatory Responses

Implication of the Autophagy-Related Protein Beclin1 in the Regulation of EcoHIV Replication and Inflammatory Responses

Role of Autophagy in HIV-1 and Drug Abuse-Mediated Neuroinflammaging

Methamphetamine and HIV-1 Tat Protein Synergistically Induce Endoplasmic Reticulum Stress to Promote TRIM13-Mediated Neuronal Autophagy

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