Author Correction: 7,8-Dihydroxyflavone improves neuropathological changes in the brain of Tg26 mice, a model for HIV-associated neurocognitive disorder

This review presents an up-to-date assessment of the role of the tryptophan metabolic and catabolic pathways in neurodegenerative disease and HIV-associated neurocognitive disorder. The kynurenine pathway and the effects of each of its enzymes and products are reviewed. The differential expression of the kynurenine pathway in cells within the brain, including inflammatory cells, is explored given the increasing recognition of the importance of inflammation in neurodegenerative disease. An overview of common mechanisms of neurodegeneration is presented before a review and discussion of the evidence for a pathogenetic role of the kynurenine pathway in Alzheimer's disease, HIV-associated neurocognitive disorder, Huntington's disease, motor neurone disease, and Parkinson's disease.

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7,8-dihydroxyflavone Improves Neuropathological Changes in the Brain of Tg26 Mice, A Model for HIV-associated Neurocognitive Disorder

10.21203/rs.3.rs-91556/v1 ◽

2020 ◽

Author(s):

Joseph Bryant ◽

Sanketh Andhavarapu ◽

Christopher Bever ◽

Poornachander Guda ◽

Akhil Katuri ◽

...

Keyword(s):

Therapeutic Potential ◽

Brain Regions ◽

Mitochondrial Damage ◽

Data Sets ◽

Neurocognitive Disorder ◽

Hiv Patients ◽

Neuroprotective Effects ◽

Downstream Signaling ◽

Hiv Associated Neurocognitive Disorder ◽

The Brain

Abstract Background: The combined antiretroviral therapy (cART) era has significantly increased the lifespan of HIV patients, turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In HIV+ patients, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile.Methods: We investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. We immunohistochemically stained brain tissue sections from vehicle-treated wild type (WT), vehicle-treated Tg26, and DHF (5 mg/kg, i.p)-treated Tg26 mice to examine activation of TrkB and downstream signaling, expression of HIV-1 chemokine co-receptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. A one-way ANOVA with a Bonferroni Comparison post-hoc test was performed to analyze the data sets. Results: In the brain regions of Tg26 mice, we observed astrogliosis, increased CXCR4 and CCR5 expression, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB-Akt-NFkB signaling pathway in mediating these pathological hallmarks.Conclusions: Our study provides an overview of how targeting BDNF-TrkB signaling in the pathophysiology of HAND may be relevant for future therapies, and sheds light on 7,8 Dihydroxyflavone as a potential adjunct therapeutic agent to current antiviral therapy.

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7,8-Dihydroxyflavone improves neuropathological changes in the brain of Tg26 mice, a model for HIV-associated neurocognitive disorder

Scientific Reports ◽

10.1038/s41598-021-97220-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Joseph Bryant ◽

Sanketh Andhavarapu ◽

Christopher Bever ◽

Poornachander Guda ◽

Akhil Katuri ◽

...

Keyword(s):

Therapeutic Potential ◽

Brain Regions ◽

Future Research ◽

Neurocognitive Disorder ◽

Neuroprotective Effects ◽

Antiviral Therapies ◽

Combined Antiretroviral Therapy ◽

Hiv Associated Neurocognitive Disorder ◽

The Brain

AbstractThe combined antiretroviral therapy era has significantly increased the lifespan of people with HIV (PWH), turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In PWH, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile. Therefore, we investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. In these brain regions, we observed astrogliosis, increased expression of chemokine HIV-1 coreceptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Moreover, our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB–Akt–NFkB signaling pathway in mediating these pathological hallmarks. These findings guide future research as DHF shows promise as a TrkB agonist treatment for HAND patients in adjunction to the current antiviral therapies.

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Can Individualized-Targeted Computerized Cognitive Training Benefit Adults with HIV-Associated Neurocognitive Disorder? The Training on Purpose Study (TOPS)

AIDS and Behavior ◽

10.1007/s10461-021-03230-y ◽

2021 ◽

Author(s):

David E. Vance ◽

Pariya L. Fazeli ◽

Andres Azuero ◽

Virginia G. Wadley ◽

James L. Raper ◽

...

Keyword(s):

Cognitive Training ◽

Neurocognitive Disorder ◽

Computerized Cognitive Training ◽

Hiv Associated Neurocognitive Disorder

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Scaling Up Information Sharing on HIV-Associated Neurocognitive Disorder: Raising Awareness and Knowledge Among Key Stakeholders

SAGE Open ◽

10.1177/21582440211016898 ◽

2021 ◽

Vol 11 (2) ◽

pp. 215824402110168

Author(s):

Renato M. Liboro ◽

Paul A. Shuper ◽

Lori E. Ross

Keyword(s):

Health Care ◽

Information Sharing ◽

Service Providers ◽

Scale Up ◽

People Living With Hiv ◽

Neurocognitive Disorder ◽

Public Health Informatics ◽

Raising Awareness ◽

Hiv Associated Neurocognitive Disorder ◽

Hiv Aids

Although the majority of specialists and researchers in the field of HIV/AIDS are aware and knowledgeable about HIV-associated neurocognitive disorder (HAND) as a condition that affects as much as 50% of people living with HIV/AIDS (PLWH), research has documented that many health care and service providers who work directly with PLWH are either unaware of HAND or believe they do not know enough information about HAND to effectively support their clients experiencing neurocognitive challenges. Based on the findings of a qualitative study that interviewed 33 health care and service providers in HIV/AIDS services to identify and examine their awareness and knowledge on HAND, this article argues for utilizing a combination of Public Health Informatics principles; communication techniques, propagation strategies, and recognized approaches from Implementation and Dissemination Science; and social media and online discussion platforms, in addition to traditional Knowledge Mobilization strategies, to scale up information sharing on HAND among all relevant stakeholders. Increasing information sharing among stakeholders would be an important step to raising awareness and knowledge on HAND, and consequently, improving care, services, and support for PLWH and neurocognitive issues.

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Genetic variation of matrix metalloproteinase enzyme in HIV-associated neurocognitive disorder

Gene ◽

10.1016/j.gene.2019.02.057 ◽

2019 ◽

Vol 698 ◽

pp. 41-49 ◽

Cited By ~ 1

Author(s):

HariOm Singh ◽

Sumitra Nain ◽

Asha Krishnaraj ◽

Sonam Lata ◽

T.N. Dhole

Keyword(s):

Genetic Variation ◽

Matrix Metalloproteinase ◽

Neurocognitive Disorder ◽

Hiv Associated Neurocognitive Disorder

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Effects of a 12-week aerobic exercise programme on HIV-associated neurocognitive disorder in Nigeria: A protocol for randomized controlled trial (Preprint)

10.2196/preprints.29230 ◽

2021 ◽

Author(s):

Martins Nweke ◽

Nombeko Mshunqane ◽

Nalini Govender ◽

Aderonke Akineplu ◽

Adesola Oginniyi

Keyword(s):

Aerobic Exercise ◽

Repeated Measures ◽

Controlled Trial ◽

Exercise Programme ◽

Moderate Intensity ◽

Behavioural Intervention ◽

Neurocognitive Disorder ◽

Neurocognitive Performance ◽

Southeastern Nigeria ◽

Hiv Associated Neurocognitive Disorder

BACKGROUND The introduction of antiretroviral therapy (ART) has led to a drastic fall in the incidence of HIV-associated dementia. However, less severe but limiting forms of HIV-associated neurocognitive disorder (HAND) continues to be prevalent even with the use of ART. Aerobic exercise, a behavioural intervention may be a beneficial and effective complement to ART in the management of HAND. In HIV-negative individuals, aerobic exercise mitigates pathogenic changes similar to those of HAND. OBJECTIVE This protocol describes a randomized clinical trial designed to determine the effect of a 12-week aerobic exercise programme on HAND in Southeastern Nigeria. METHODS A minimum of seventy-six patients diagnosed with HAND will be randomized into aerobic exercise and control groups. Aerobic exercise will be carried out on a stationary bicycle ergometer at moderate intensity, three times a week for 12-weeks. Primary outcomes are neurocognitive performance, CD4-count and viral load. Evaluation of post-exercise neurocognitive performance will be undertaken using reliable neuropsychological tests relevant to PLWHIV, in line with Frascati criteria. Secondary outcomes such as quality of life, and activity limitation and social participation will be assessed using the WHOQOL-Bref, and the Oxford Participation and Activities questionnaire respectively. Data will be subjected to exploratory statistics to test for normality and homogeneity. The effect of the exercise programme on HAND will be analysed using two-way repeated-measures ANOVA, with Bonferroni’s correction. Within-group comparison will be undertaken using paired sampled t-test. RESULTS Enrollment began on 18th January 2021. Recruitment has been completed. The trial is ongoing and will be completed in July 2021 CONCLUSIONS The study will provide valuable information about the effect of aerobic exercise on HAND thus verifying the suitability of aerobic exercise as a complementary therapy for mitigating neurocognitive disorder among PLWHIV. Data from the study will be useful in pursuit of debate on the necessity of a sponsored rehabilitation arm in ART clinics. CLINICALTRIAL The study was registered with the PAN African Trial Registry (PACTR) on the 1stth September 2020. The registration ID is PACTR202009483415745.

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