» Articles » PMID: 35496912

Mitoapocynin Attenuates Organic Dust Exposure-Induced Neuroinflammation and Sensory-Motor Deficits in a Mouse Model

Overview
Specialty Cell Biology
Date 2022 May 2
PMID 35496912
Authors
Affiliations
Soon will be listed here.
Abstract

Increased incidences of neuro-inflammatory diseases in the mid-western United States of America (USA) have been linked to exposure to agriculture contaminants. Organic dust (OD) is a major contaminant in the animal production industry and is central to the respiratory symptoms in the exposed individuals. However, the exposure effects on the brain remain largely unknown. OD exposure is known to induce a pro-inflammatory phenotype in microglial cells. Further, blocking cytoplasmic NOX-2 using mitoapocynin (MA) partially curtail the OD exposure effects. Therefore, using a mouse model, we tested a hypothesis that inhaled OD induces neuroinflammation and sensory-motor deficits. Mice were administered with either saline, fluorescent lipopolysaccharides (LPSs), or OD extract intranasally daily for 5 days a week for 5 weeks. The saline or OD extract-exposed mice received either a vehicle or MA (3 mg/kg) orally for 3 days/week for 5 weeks. We quantified inflammatory changes in the upper respiratory tract and brain, assessed sensory-motor changes using rotarod, open-field, and olfactory test, and quantified neurochemicals in the brain. Inhaled fluorescent LPS (FL-LPS) was detected in the nasal turbinates and olfactory bulbs. OD extract exposure induced atrophy of the olfactory epithelium with reduction in the number of nerve bundles in the nasopharyngeal meatus, loss of cilia in the upper respiratory epithelium with an increase in the number of goblet cells, and increase in the thickness of the nasal epithelium. Interestingly, OD exposure increased the expression of HMGB1, 3- nitrotyrosine (NT), IBA1, glial fibrillary acidic protein (GFAP), hyperphosphorylated Tau (p-Tau), and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL)-positive cells in the brain. Further, OD exposure decreased time to fall (rotarod), total distance traveled (open-field test), and olfactory ability (novel scent test). Oral MA partially rescued olfactory epithelial changes and gross congestion of the brain tissue. MA treatment also decreased the expression of HMGB1, 3-NT, IBA1, GFAP, and p-Tau, and significantly reversed exposure induced sensory-motor deficits. Neurochemical analysis provided an early indication of depressive behavior. Collectively, our results demonstrate that inhalation exposure to OD can cause sustained neuroinflammation and behavior deficits through lung-brain axis and that MA treatment can dampen the OD-induced inflammatory response at the level of lung and brain.

Citing Articles

Neuroinflammaging: A Tight Line Between Normal Aging and Age-Related Neurodegenerative Disorders.

Soraci L, Corsonello A, Paparazzo E, Montesanto A, Piacenza F, Olivieri F Aging Dis. 2024; 15(4):1726-1747.

PMID: 38300639 PMC: 11272206. DOI: 10.14336/AD.2023.1001.

References
1.
Sarkar S, Malovic E, Harishchandra D, Ghaisas S, Panicker N, Charli A . Mitochondrial impairment in microglia amplifies NLRP3 inflammasome proinflammatory signaling in cell culture and animal models of Parkinson's disease. NPJ Parkinsons Dis. 2017; 3:30. PMC: 5645400. DOI: 10.1038/s41531-017-0032-2. View

2.
Lucchini R, Dorman D, Elder A, Veronesi B . Neurological impacts from inhalation of pollutants and the nose-brain connection. Neurotoxicology. 2011; 33(4):838-41. PMC: 3387329. DOI: 10.1016/j.neuro.2011.12.001. View

3.
Ghosh A, Langley M, Harischandra D, Neal M, Jin H, Anantharam V . Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson's Disease. J Neuroimmune Pharmacol. 2016; 11(2):259-78. PMC: 4995106. DOI: 10.1007/s11481-016-9650-4. View

4.
Mahadev Bhat S, Massey N, Karriker L, Singh B, Charavaryamath C . Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling. Respir Res. 2019; 20(1):27. PMC: 6364446. DOI: 10.1186/s12931-019-0992-3. View

5.
Tani M, Glabinski A, Tuohy V, Stoler M, Estes M, Ransohoff R . In situ hybridization analysis of glial fibrillary acidic protein mRNA reveals evidence of biphasic astrocyte activation during acute experimental autoimmune encephalomyelitis. Am J Pathol. 1996; 148(3):889-96. PMC: 1861709. View