Anti-HIV drugs promote β-amyloid deposition and impair learning and memory in BALB/c mice
| Autor: | Simo S. Zulu, Oualid Abboussi, Nicola Simola, William M. U. Daniels, Musa V. Mabandla |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
AIDS Dementia Complex
Nevirapine Amyloid Anti-HIV Agents Amyloid beta Administration Oral Morris water navigation task HIV Infections Pharmacology medicine.disease_cause Hippocampus BALB/c Lipid peroxidation Amyloid beta-Protein Precursor Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Memory medicine Amyloid precursor protein Animals Aspartic Acid Endopeptidases Cognitive Dysfunction Maze Learning Tenofovir Biological Psychiatry 030304 developmental biology Mice Inbred BALB C 0303 health sciences Amyloid beta-Peptides biology Learning Disabilities business.industry Brain biology.organism_classification Disease Models Animal Psychiatry and Mental health chemistry HIV-1 biology.protein Female Lipid Peroxidation Amyloid Precursor Protein Secretases business 030217 neurology & neurosurgery Oxidative stress medicine.drug |
| Zdroj: | Acta Neuropsychiatrica. 32:257-264 |
| ISSN: | 1601-5215 0924-2708 |
| DOI: | 10.1017/neu.2020.19 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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