Differential effects of inhalation exposure to PM2.5 on hypothalamic monoamines and corticotrophin releasing hormone in lean and obese rats

• Published in: Neurotoxicology (Park Forest South) 2013-05, Vol.36, p.106-111
• Main Authors: Balasubramanian, Priya, Sirivelu, Madhu P., Weiss, Kathryn A., Wagner, James G., Harkema, Jack R., Morishita, Masako, MohanKumar, P.S., MohanKumar, Sheba M.J.
• Format: Article
• Language: English
• Subjects: Air; Animals; Biogenic Monoamines - metabolism; Biological and medical sciences; Body Weight - drug effects; Cardiovascular risk; Chromatography, High Pressure Liquid; Corticotropin-Releasing Hormone - metabolism; Disease Models, Animal; Elementary Particles - adverse effects; Environmental pollutants toxicology; Enzyme-Linked Immunosorbent Assay; Hypothalamus - drug effects; Inhalation Exposure; Male; Medical sciences; Metabolic diseases; Obesity; Obesity - pathology; Obesity - physiopathology; Particulate matter; Rats; Repeated exposure; Stress axis; Sympathetic nervous system; Time Factors; Toxicology
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2012.02.016

► There is marked activation of the paraventricular nucleus after acute exposure to PM2.5 as indicated by increases in the levels of neurotransmitters such as norepinephrine and 5-hydroxyindole acetic acid. However, this activation is not apparent after 3 day exposure to PM2.5 in a lean rat model (Brown Norway rat). ► CRH levels follow the neurotransmitter pattern in these lean rats as well. Acute exposure to PM2.5 produces an increase in CRH levels, while subchronic exposures do not. ► In obese rats, subchronic exposure to PM2.5 increases norepinephrine levels in the paraventricular nucleus but does not increase CRH levels. ► Possible reasons for these differences between lean and obese rats are discussed. 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 t