Sera from people with HIV and depression induce commensurate metabolic alterations in astrocytes: toward precision diagnoses and therapies.

Autor: Laird AE; Department of Psychiatry, University of California, San Diego, CA, USA., Le AA; Department of Psychiatry, University of California, San Diego, CA, USA., Kulbe JR; Department of Psychiatry, University of California, San Diego, CA, USA., Umlauf A; Department of Psychiatry, University of California, San Diego, CA, USA., Sagarian M; Department of Psychiatry, University of California, San Diego, CA, USA., Spencer M; Department of Psychiatry, University of California, San Diego, CA, USA., Sathe A; Department of Psychiatry, University of California, San Diego, CA, USA., Grelotti DJ; Department of Psychiatry, University of California, San Diego, CA, USA., Iudicello J; Department of Psychiatry, University of California, San Diego, CA, USA., Henry B; Department of Psychiatry, University of California, San Diego, CA, USA., Ellis RJ; Department of Psychiatry, University of California, San Diego, CA, USA.; Department of Neurosciences, University of California, San Diego, CA, USA., Fields JA; Department of Psychiatry, University of California, San Diego, CA, USA.
Jazyk: angličtina
Zdroj: NeuroImmune pharmacology and therapeutics [NeuroImmune Pharm Ther] 2024 Mar 27; Vol. 3 (2), pp. 113-128. Date of Electronic Publication: 2024 Mar 27 (Print Publication: 2024).
DOI: 10.1515/nipt-2024-0001
Abstrakt: Objectives: People with HIV (PWH) have high rates of depression and neurocognitive impairment (NCI) despite viral suppression on antiretroviral therapy (ART). Mounting evidence suggests that immunometabolic disruptions may contribute to these conditions in some PWH. We hypothesized that metabolic dysfunction in astrocytes is associated with depressive symptoms and cognitive function in PWH.
Methods: Human astrocytes were exposed to sera from PWH ( n =40) with varying degrees of depressive symptomatology and cognitive function. MitoTracker TM Deep Red FM (MT) was used to visualize mitochondrial activity and glial fibrillary acidic protein (GFAP) as an indicator of astrocyte reactivity using the high-throughput fluorescent microscopy and image analyses platform, CellInsight CX5 (CX5). The Seahorse platform was used to assess glycolytic and mitochondrial metabolism.
Results: More severe depression, as indexed by higher Beck's Depression Inventory (BDI-II) scores, was associated with lower MT signal measures. Better cognitive function, as assessed by neuropsychiatric testing t-scores, was associated with increased MT signal measures. GFAP intensity negatively correlated with several cognitive t-scores. Age positively correlated with (higher) MT signal measures and GFAP intensity. Worse depressive symptoms (higher BDI-II scores) were associated with decreased oxygen consumption rate and spare respiratory capacity, concomitant with increased extracellular acidification rate in astrocytes.
Conclusions: These findings show that factors in the sera of PWH alter mitochondrial activity in cultured human astrocytes, suggesting that mechanisms that alter mitochondrial and astrocyte homeostasis can be detected peripherally. Thus, in vitro cultures may provide a model to identify neuropathogenic mechanisms of depression or neurocognitive impairment in PWH and test personalized therapeutics for neurologic and psychiatric disorders.
Competing Interests: Competing interests: UCSD (inventor: Jerel Adam Fields) has a patent pending related to this work.
(© 2024 the author(s), published by De Gruyter, Berlin/Boston.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje