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Immune Suppression of Glia Maturation Factor Reverses Behavioral Impairment, Attenuates Amyloid Plaque Pathology and Neuroinflammation in an Alzheimer’s Disease Mouse Model

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Abstract

Alzheimer’s disease (AD) is an irreversible progressive neurodegenerative disorder recognized by accumulation of amyloid-plaques (APs) and neurofibrillary tangles (NFTs) and eventually loss of memory. Glia maturation factor (GMF), a neuroinflammatory protein first time isolated and cloned in our laboratory plays an important role in the pathogenesis of AD. However, no studies have been reported on whether anti-GMF antibody administration could downregulate neuroinflammation and attenuate amyloid pathology in AD brain. We investigated the potential effect of single dose of (2 mg/kg b.wt/mouse) intravenously (iv) injected with anti-GMF antibodyon cognitive function, neuroprotection, neuroinflammation and Aβ load in the brain of 9-month-old 5XFAD mice. Following 4 weeks of anti-GMF antibody delivery in mice, we found reduced expression of GMF, astrocytic glial fibrillary acidic protein (GFAP) and microglial ionizing calcium binding adaptor molecule 1 (Iba1) as well as improvement inneuroinflammatory response via inhibition of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) production and amyloid pathology in the cerebral cortex and hippocampal CA1 region of 5XFAD mice. Correspondingly, blockade of GMF function with anti-GMF antibody improved spatial learning, memory, and long-term recognition memory in 5XFAD mice. The present study demonstrates that the immune checkpoint blockade of GMF function with anti-GMF antibody coordinates anti-inflammatory effects to attenuate neurodegeneration in the cortex and hippocampal CA1 region of 5XFAD mouse brain. Further, our data suggest, that pharmacological immune neutralization of GMF is a promising neuroprotective strategy totherapeutically target neuroinflammation and neurodegeneration in AD.

5XFAD mice Polyclonal anti-GMF antibody

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Funding

This study was supported by the National Institutes of Health Grants AG048205 and VA Research Career Scientist Award to Asgar Zaheer.

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Authors and Affiliations

  1. Department of Neurology and Center for Translational Neuroscience, School of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO, USA

    Mohammad Ejaz Ahmed, Govindhasamy Pushpavathi Selvakumar, Ramasamy Thangavel, Duraisamy Kempuraj, Sudhanshu P. Raikwar, Smita Zaheer, Shankar Iyer & Asgar Zaheer

  2. Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA

    Mohammad Ejaz Ahmed, Govindhasamy Pushpavathi Selvakumar, Ramasamy Thangavel, Duraisamy Kempuraj, Sudhanshu P. Raikwar, Shankar Iyer & Asgar Zaheer

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  1. Mohammad Ejaz Ahmed
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  2. Govindhasamy Pushpavathi Selvakumar
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  3. Ramasamy Thangavel
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  8. Asgar Zaheer
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Correspondence to Asgar Zaheer.

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Ahmed, M.E., Selvakumar, G.P., Thangavel, R. et al. Immune Suppression of Glia Maturation Factor Reverses Behavioral Impairment, Attenuates Amyloid Plaque Pathology and Neuroinflammation in an Alzheimer’s Disease Mouse Model. J Neuroimmune Pharmacol 16, 363–375 (2021). https://doi.org/10.1007/s11481-020-09929-4

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