ArticlePloS one2020
The peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone, ameliorates neurofunctional and neuroinflammatory abnormalities in a rat model of Gulf War Illness.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 24 citations in OpenAlex.
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- A Mouse Model of Temporal Lobe Contusion.Journal of neurotrauma · 2025Article
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- Electroacupuncture activates the peroxisome proliferators-activated receptor pathway to improve the phenotype of cerebral palsy.CNS neuroscience & therapeutics · 2024Article
- Identification of Genes Crucial for Biological Processes in Breast Cancer Liver Metastasis Relapse.International journal of molecular sciences · 2024Article
- Correlation of HIV-Induced Neuroinflammation and Synaptopathy with Impairment of Learning and Memory in Mice with HAND.Journal of clinical medicine · 2023Article
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- Pathophysiological basis and promise of experimental therapies for Gulf War Illness, a chronic neuropsychiatric syndrome in veterans.Psychopharmacology · 2023Review
- Role of JAK-STAT and PPAR-Gamma Signalling Modulators in the Prevention of Autism and Neurological Dysfunctions.Molecular neurobiology · 2022Review
- Polarization of Microglia and Its Therapeutic Potential in Sepsis.International journal of molecular sciences · 2022Review
- Novel Pharmacological Approaches to the Treatment of Depression.Life (Basel, Switzerland) · 2022Review
- The β-adrenergic receptor blocker and anti-inflammatory drug propranolol mitigates brain cytokine expression in a long-term model of Gulf War Illness.Life sciences · 2021Article
- Peroxisome proliferator-activated receptor gamma: a novel therapeutic target for cognitive impairment and mood disorders that functions via the regulation of adult neurogenesis.Archives of pharmacal research · 2021Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGulf War (GW) Illness (GWI) is a debilitating condition with a complex constellation of immune, endocrine and neurological symptoms, including cognitive impairment, anxiety and depression. We studied a novel model of GWI based on 3 known common GW exposures (GWE): (i) intranasal lipopolysaccharide, to which personnel were exposed during desert sand storms; (ii) pyridostigmine bromide, used as prophylaxis against chemical warfare; and (iii) chronic unpredictable stress, an inescapable element of war. We used this model to evaluate prophylactic treatment with the PPARγ agonist, rosiglitazone (ROSI).
methodsRats were subjected to the three GWE for 33 days. In series 1 and 2, male and female GWE-rats were compared to naïve rats. In series 3, male rats with GWE were randomly assigned to prophylactic treatment with ROSI (GWE-ROSI) or vehicle. After the 33-day exposures, three neurofunctional domains were evaluated: cognition (novel object recognition), anxiety-like behaviors (elevated plus maze, open field) and depression-like behaviors (coat state, sucrose preference, splash test, tail suspension and forced swim). Brains were analyzed for astrocytic and microglial activation and neuroinflammation (GFAP, Iba1, tumor necrosis factor and translocator protein). Neurofunctional data from rats with similar exposures were pooled into 3 groups: naïve, GWE and GWE-ROSI.
resultsCompared to naïve rats, GWE-rats showed significant abnormalities in the three neurofunctional domains, along with significant neuroinflammation in amygdala and hippocampus. There were no differences between males and females with GWE. GWE-ROSI rats showed significant attenuation of neuroinflammation and of some of the neurofunctional abnormalities.
conclusionThis novel GWI model recapitulates critical neurofunctional abnormalities reported by Veterans with GWI. Concurrent prophylactic treatment with ROSI was beneficial in this model.
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