A miRNA Signature for Cognitive Deficits and Alcohol Use Disorder in Persons Living with HIV/AIDS

Abstract

HIV-associated neurocognitive disorders (HAND) affects more than half of persons living with HIV-1/AIDS (PLWHA). Identification of biomarkers representing the cognitive status of PLWHA is a critical step for implementation of successful cognitive, behavioral and pharmacological strategies to prevent onset and progression of HAND. However, the presence of co-morbidity factors in PLWHA, the most common being substance abuse, can prevent the identification of such biomarkers. We have optimized a protocol to profile plasma miRNAs using quantitative RT-qPCR and found a miRNA signature with very good discriminatory ability to distinguish PLWHA with cognitive impairment from those without cognitive impairment. Here, we have evaluated this miRNA signature in PLWHA with alcohol use disorder (AUD) at LSU Health Sciences Center (LSUHSC). The results show that AUD is a potential confounding factor for the miRNAs associated with cognitive impairment in PLWHA. Furthermore, we have investigated the miRNA signature associated with cognitive impairment in an independent cohort of PLWHA using plasma samples from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) program. Despite differences between the two cohorts in socioeconomic status, AUD, and likely misuse of illicit or prescription drugs, we validated a miRNA signature for cognitive deficits found at LSUHSC in the CHARTER samples.

A hypothesis-generating scoping review of miRs identified in both multiple sclerosis and dementia, their protein targets, and miR signaling pathways

“…In this study, MiR hsa-let-7 g-5p was among the miRs showing significant correlation with MMSE at baseline and it predicted decline at the individual level [209]. Finally, MiR-let-7b-5p in serum successfully differentiated cognitively impaired and cognitively intact HIV+ people who were diagnosed with impairment based on the Multicenter AIDS Cohort Study (MACS) screening battery [210].…”

Potential Associations Among Alteration of Salivary miRNAs, Saliva Microbiome Structure, and Cognitive Impairments in Autistic Children

“…For instance, miR-141-3p expression progressively increases in a time-dependent manner in mouse models of post-stroke social isolation [ 88 ], and members of the miR-29 family increased their expression during the healing process of oral palatal mucosal wounds [ 89 ]. Moreover, decreasing plasmatic let-7b-5p correlated strongly with cognitive impairment in the presence of severe alcohol use disorder [ 90 ] and it was also related to high stress conditions [ 91 ]. Levels of circulating miR-451a in the blood of depressed patients were found reduced and negatively associated with the Hamilton Depression Scale that is used to rate the severity of depression: a depression-like phenotype is often observed in autistic patients [ 92 , 93 ].…”

Pilot study identifying circulating miRNA signature specific to alcoholic chronic pancreatitis and its implication on alcohol‐mediated pancreatic tissue injury

“…Among the other miRNA candidates, miR‐361‐5p, also an antiautophagy miRNA, has been reported to be upregulated in acute pancreatitis patients 28 . miR‐143‐3p also found to be upregulated in rheumatoid arthritis and reported to be upregulated upon alcohol consumption 29 . miR‐338‐3p, miR‐30a‐3p, and miR‐194‐5p also act as anti‐inflammatory and antifibrotic miRNAs, reported to be induced by alcohol, while miR‐216b‐5p and miR‐28‐5p are pro‐inflammatory and pro‐fibrotic miRNAs and have been shown earlier to be acting as markers of acute pancreatic injury and inflammation.…”