Evidence map›Paper›PMID 41223977›Full record

ArticleBrain, behavior, and immunity2026

Osteopontin knockdown reverses HIV-induced cognitive deficits and influences motivation-related behavior.

Srivaishnavi Loganathan, Menghan Sun, Catalina Argandona Lopez, Jasmine Wangui, Aynur Shirmamedova, Autumn Johnson, Pearl Louie, Zachary Pelland, Raquia Alize-Hunt, Xiaolei Zhu and 2 more

Abstract read
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In one paragraph

Article in Brain, behavior, and immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Srivaishnavi LoganathanDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Menghan SunDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Catalina Argandona LopezDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Jasmine WanguiDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Aynur ShirmamedovaDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Autumn JohnsonDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Pearl LouieDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Zachary PellandDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Raquia Alize-HuntDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Xiaolei ZhuPsychoimmune Biology Program, Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Dani SmithPsychological and Brain Sciences, Johns Hopkins University, Baltimore, MD, USA.
Amanda M BrownDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Richard T. Johnson Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: abrown76@jhmi.edu.

Funding

Therapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Leah Helane Rubin · 2006 to 2026
$33.2M
The HIV-Osteopontin-HAND Triad: Inflammation and Neuronal Injury in the BrainR01NS102006 · NINDS · JOHNS HOPKINS UNIVERSITY · PI AMANDA MARIA BROWN · 2016 to 2026
$6.4M
The role of microglial glutaminase in HIV-induced sleep deficitsR01HL180044 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Xiaolei Zhu · 2025 to 2026
$1.4M
NHLBI NIH HHS R01 HL180044NIMH NIH HHS P30 MH075673NINDS NIH HHS R01 NS102006
6 · The paper itself

Abstract

The neurological complications of HIV or NeuroHIV, representing a spectrum of disorders in people living with HIV, are characterized by memory impairments and cognitive decline. Osteopontin/secreted phosphoprotein 1 (OPN/SPP1), a multifunctional cytokine-like protein secreted by multiple cell types in and outside the central nervous system (CNS), is highly elevated in NeuroHIV and other well-known neurodegenerative disorders. Additionally, previous neuroimaging studies have demonstrated a role for OPN in regulating neuroinflammatory signaling. However, the potential links between CNS-specific functions of OPN and behavior remain unclear. In this study, we used NSG immunodeficient mice (hu-mice) engrafted as neonates with HIV-susceptible human CD34 + hematopoietic stem cells (HSCs) to test the hypotheses that chronic viral infection impairs cognitive function and that systemic disruption of OPN expression can ameliorate the resulting behavioral deficits. We found that HIV-infected hu-mice treated with inhibitory OPN-aptamers to knock down OPN exhibited altered exploratory and anxiety-related behavior compared to uninfected animals. A synergistic relationship between HIV and OPN impaired cognitive performance in an object recognition memory task that was not observed in uninfected mice. The knockdown of OPN expression alleviated this recognition deficit. Interestingly, only the HIV-infected OPN knockdown group showed a marked reduction in motivation/self-care related behavior. Additionally, we found reduced OPN expression in cells located in the midbrain ventral tegmental area of HIV-infected mice, demonstrating for the first time, the systemic delivery of functional aptamers to the brain. Notably, there were no significant differences in OPN levels in similarly treated uninfected mice. Notably, a decrease in tyrosine hydroxylase (TH) expression in midbrain dopaminergic neurons of OPN knockdown compared to OPN wildtype mice, irrespective of HIV infection status was foundsuggests a potential gene expression regulatory link between OPN and TH. These findings highlight the multifaceted role of OPN in HIV-associated neurobehavioral dysfunction, suggesting context-dependent contributions to both cognitive and apathy-based processes.

Indexed as

Cognitive DysfunctionHIV InfectionsMotivationOsteopontinAnimalsAnxietyBehavior, AnimalCognitionGene Knockdown TechniquesHumansMaleMiceMice, SCIDOsteopontinSpp1 protein, mouseCognitive impairmentHematopoietic stem cellsHIV-1Humanized NSG miceMidbrainNeuroinflammationTyrosine hydroxylase

Identifiers

PMID41223977
PMCPMC12671066

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.