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

Abstract

-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 MnCl 2 aerosol in a nose-only inhalation chamber for 3 weeks (1.2 μm, 39 mg/m 3 ). 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/m 3 Mn for 3 weeks induced mild lung injury and modulation of dopamine transporter expression in the brain, without altering motor activity.

Air Pollution-Related Brain Metal Dyshomeostasis as a Potential Risk Factor for Neurodevelopmental Disorders and Neurodegenerative Diseases

“…Intranasal instillation of MnCl 2 solute (40 µL of aqueous 200mM) in rats resulted in olfactory bulb uptake as well as the impairment of olfactory discrimination [454]. Short term exposure of male Sprague Dawley rats (nose only to 1.2 µm, 39 mg/m 3 for 5 days/week for 3 weeks) produced a Mn concentration gradient decreasing from olfactory bulb to striatum; while this exposure did not produce changes in rotarod performance, reductions in dopamine transporter levels were present in striatum [455]. Of direct relevance to PD, over the course of exposure of adult male Wistar rats to 0.04 M MnCl 2 and 0.02 M Mn(OAc) 3 for 1 h 3× weekly for 6 months (72 inhalations), beam walk test time increased significantly, and numbers of successful reaches in a single-pellet reaching task declined.…”

The Role of Nicotinic Receptors in the Attenuation of Autism‐Related Behaviors in a Murine BTBR T + tf/J Autistic Model

“…In our study, separate groups of mice (n = 6-8 mice per group) were used for each test were conducted under blind conditions. The behavioral pharmacological tests included, a self-grooming test and a marble-burying test to assess repetitive behavior [McFarlane et al, 2008;Angoa-Pérez, Kane, Briggs, Francescutti, & Kuhn, 2013]; a three-chamber social interaction test to measure sociability [Kaidanovich-Beilin, Lipina, Vukobradovic, Roder, & Woodgett, 2011]; the LA [York, Blevins, McNeil, & Freund, 2013], and a RR test for motor coordination [Dunham & Miya, 1957;Saputra et al, 2016] in mice.…”

“…Rotarod test for motor performance and coordination. The rotarod (RR) test was used to measure the motor coordination of rodents [Dunham & Miya, 1957;Saputra et al, 2016]. In short, it was measured using an automated accelerating RR apparatus (Panlab Harvard Apparatus, Barcelona, Spain).…”

Effects of Aging on Angiogenic and Muscle Growth-Related Factors in Naturally Aged Rat Skeletal Muscles

“…The duration and number of times that the rats fell from the bar were recorded, as described previously. 16)…”