title: Differential effects of inhalation exposure to PM2.5 on hypothalamic monoamines and corticotrophin releasing hormone in lean and obese rats.
abstract: Acute exposure to airborne pollutants, especially particulate matter (PM2.5) is known to increase hospital admissions for cardiovascular conditions, increase cardiovascular related mortality and predispose the elderly and obese individuals to cardiovascular conditions. The mechanisms by which PM2.5 exposure affects the cardiovascular system is not clear. Since the autonomic system plays an important role in cardiovascular regulation, we hypothesized that PM2.5 exposure most likely activates the paraventricular nucleus (PVN) of the hypothalamus to cause an increase in sympathetic nervous system and/or stress axis activity. We also hypothesized that these changes may be sustained in obese rats predisposing them to higher cardiovascular risk. To test this, adult male Brown Norway (BN) rats were subjected to one day or three days of inhalation exposures to filtered air (FA) or concentrated air particulate (CAP) derived from ambient PM2.5. Corpulent JCR-LA rats were exposed to FA or CAP for four days. Animals were sacrificed 24h after the last inhalation exposure. Their brains were removed, frozen and sectioned. The PVN and median eminence (ME) were microdissected. PVN was analyzed for norepinephrine (NE), dopamine (DA) and 5-hydroxy-indole acetic acid (5-HIAA) levels using HPLC-EC. ME was analyzed for corticotrophin releasing hormone (CRH) levels by ELISA. One day exposure to CAP increased NE levels in the PVN and CRH levels in the ME of BN rats. Repeated exposures to CAP did not affect NE levels in the PVN of BN rats, but increased NE levels in JCR/LA rats. A similar pattern was observed with 5-HIAA levels. DA levels on the other hand, were unaffected in both BN and JCR/LA strains. These data suggest that repeated exposures to PM2.5 continue to stimulate the PVN in obese animals but not lean rats.
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, Michigan State University, E. Lansing, MI 48824, United States.
authors.forename: Priya
authors.initials: P
authors.lastname: Balasubramanian
authors.forename: Madhu P
authors.initials: MP
authors.lastname: Sirivelu
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Weiss
authors.forename: James G
authors.initials: JG
authors.lastname: Wagner
authors.forename: Jack R
authors.initials: JR
authors.lastname: Harkema
authors.forename: Masako
authors.initials: M
authors.lastname: Morishita
authors.forename: P S
authors.initials: PS
authors.lastname: Mohankumar
authors.forename: Sheba M J
authors.initials: SM
authors.lastname: Mohankumar
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004195:Disease Models, Animal; D004601:Elementary Particles / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D007031:Hypothalamus / Q000187:drug effects; D019570:Inhalation Exposure; D008297:Male; D009765:Obesity / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D013997:Time Factors
chemical_list: D015306:Biogenic Monoamines; D003346:Corticotropin-Releasing Hormone