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Anti-HIV drugs promote β-amyloid deposition and impair learning and memory in BALB/c mice

Published online by Cambridge University Press:  07 May 2020

S.S. Zulu Open the ORCID record for S.S. Zulu [Opens in a new window] ,
O. Abboussi ,
N. Simola ,
M.V. Mabandla  and
W.M.U. Daniels
S.S. Zulu*
Affiliation:
School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, South Africa
O. Abboussi
Affiliation:
Division of Neuroscience, School of Medicine, Ninewells Hospital, University of Dundee, Dundee, UK
N. Simola
Affiliation:
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
M.V. Mabandla
Affiliation:
School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, South Africa
W.M.U. Daniels
Affiliation:
School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
*
Author for correspondence: S.S. Zulu, Emails: [email protected] or [email protected]
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Abstract

Objectives:

Growing evidence suggested that antiretroviral (ARV) drugs may promote amyloid beta (Aβ) accumulation in HIV-1-infected brain and the persistence of HIV-associated neurocognitive disorders (HANDs). It has also been shown that lipid peroxidation upregulates β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) expression and subsequently promotes Aβ peptide production. In the present study, we examined whether chronic exposure to the anti-HIV drugs tenofovir disoproxil fumarate (TDF) and nevirapine induces lipid peroxidation thereby promoting BACE1 and Aβ generation and consequently impair cognitive function in mice.

Methods:

TDF or nevirapine was orally administered to female BALB/c mice once a day for 8 weeks. On the 7th week of treatment, spatial learning and memory were assessed using the Morris water maze test. The levels of lipid peroxidation, BACE1, amyloid β 1-42 (Aβ1-42) and Aβ deposits were measured in the hippocampal tissue upon completion of treatment.

Results:

Chronic administration of nevirapine induced spatial learning and memory impairment in the Morris water maze test, whereas TDF did not have an effect. TDF and nevirapine administration increased hippocampal lipid peroxidation and Aβ1-42 concentration. Nevirapine further upregulated BACE1 expression and Aβ deposits.

Conclusion:

Our results suggest that chronic exposure to TDF and nevirapine contributes to hippocampal lipid peroxidation and Aβ accumulation, respectively, as well as spatial learning and memory deficits in mice even in the absence of HIV infection. These findings further support a possible link between ARV drug toxicity, Aβ accumulation and the persistence of HANDs.

Keywords

HIV-associated cognitive motor complexreverse transcriptase inhibitorsoxidative stressbeta-secretaseamyloid
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 32 , Issue 5 , October 2020 , pp. 257 - 264
Copyright
© Scandinavian College of Neuropsychopharmacology 2020

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