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.

Fig 1. Effect of PM 2.5 exposure on body weights in BN and JCR/LA rats

A. Body weights in BN rats compared to JCR/LA rats. There were no treatment differences, but only strain differences. B. Body weight differences between the 2 age groups of JCR/LA rats. Older rats were heavier than the younger rats. There were no treatment differences. ‘a’ indicates p<0.05 compared to BN rats or younger JCR/LA rats.

Fig 2. Effect of PM2.5 exposure on Norepinephrine levels in the PVN

A. NE levels in BN rats after single and multiple day PM_2.5 exposure. There were significant increases after 1 day exposure between treatments, but not after 3 day exposure. ‘a’ indicates significant difference from acute-air treated group, p<0.05. B. NE levels in the PVN of JCR/LA rats. There were significant differences between the treatment and control group, ‘a’ indicates p<0.05.

Fig 3. Effect of multiple day PM2.5 exposure on CRH levels in the ME

A. CRH levels in BN rats after 1 and 3 day PM2.5 exposure. There were significant changes in CRH levels only after PM_2.5 exposure for 1 day. ‘a’ indicates significant difference from acute-air exposed group; p<0.05. No differences were observed in CRH levels after repeated exposures. B. CRH levels in the ME of JCR/LA rats. There were no treatment effects on CRH levels in these rats.