Short-term manganese inhalation decreases brain dopamine transporter levels without disrupting motor skills in rats

• Published in: Journal of toxicological sciences 2016/06/01, Vol.41(3), pp.391-402
• Main Authors: Saputra, Devina, Chang, JuOae, Lee, Byeong-Jae, Yoon, Jin-Ha, Kim, Jonghan, Lee, Kyuhong
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain - physiopathology; Chlorides - metabolism; Chlorides - toxicity; Dopamine Plasma Membrane Transport Proteins - metabolism; Dopamine transporter; Inhalation Exposure; Lung injury; Lung Injury - chemically induced; Lung Injury - pathology; Male; Manganese; Manganese Compounds - metabolism; Manganese Poisoning - etiology; Manganese Poisoning - metabolism; Manganese Poisoning - physiopathology; Manganese Poisoning - psychology; Motor Activity - drug effects; Motor skill; Rats; Rats, Sprague-Dawley; Receptors, Dopamine - metabolism; Risk Assessment; Rotarod Performance Test; Time Factors; Up-Regulation
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.41.391

Manganese (Mn) is used in industrial metal alloys and can be released into the atmosphere during methylcyclopentadienyl manganese tricarbonyl combustion. Increased Mn deposition in the brain after long-term exposure to the metal by inhalation is associated with altered dopamine metabolism and neurobehavioral problems, including impaired motor skills. However, neurotoxic effects of short-term exposure to inhaled Mn are not completely characterized. The purpose of this study is to define the neurobehavioral and neurochemical effects of short-term inhalation exposure to Mn at a high concentration using rats. Male Sprague-Dawley rats were exposed to MnCl2 aerosol in a nose-only inhalation chamber for 3 weeks (1.2 µm, 39 mg/m3). Motor coordination was tested on the day after the last exposure using a rotarod device at a fixed speed of 10 rpm for 2 min. Also, dopamine transporter and dopamine receptor protein expression levels in the striatum region of the brain were determined by Western blot analysis. At a rotarod speed of 10 rpm, there were no significant differences in the time on the bar before the first fall or the number of falls during the two-minute test observed in the exposed rats, as compared with controls. The Mn-exposed group had significantly higher Mn levels in the lung, blood, olfactory bulb, prefrontal cortex, striatum, and cerebellum compared with the control group. A Mn concentration gradient was observed from the olfactory bulb to the striatum, supporting the idea that Mn is transported via the olfactory pathway. Our results demonstrated that inhalation exposure to 39 mg/m3 Mn for 3 weeks induced mild lung injury and modulation of dopamine transporter expression in the brain, without altering motor activity.