Translocation of Inhaled Ultrafine Manganese Oxide Particles to the Central Nervous System

BACKGROUND: Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs; < 100 nm) and in rats with inhaled carbon UFPs suggested that solid UFPs deposited in the nose travel along the olfactory nerve to the olfactory bulb. METHODS: To determine if olfactory translocation occurs for other solid metal UFPs and assess potential health effects, we exposed groups of rats to manganese (Mn) oxide UFPs (30 nm; ~ 500 μg/m(3)) with either both nostrils patent or the right nostril occluded. We analyzed Mn in lung, liver, olfactory bulb, and other brain regions, and we performed gene and protein analyses. RESULTS: After 12 days of exposure with both nostrils patent, Mn concentrations in the olfactory bulb increased 3.5-fold, whereas lung Mn concentrations doubled; there were also increases in striatum, frontal cortex, and cerebellum. Lung lavage analysis showed no indications of lung inflammation, whereas increases in olfactory bulb tumor necrosis factor-α mRNA (~ 8-fold) and protein (~ 30-fold) were found after 11 days of exposure and, to a lesser degree, in other brain regions with increased Mn levels. Macrophage inflammatory protein-2, glial fibrillary acidic protein, and neuronal cell adhesion molecule mRNA were also increased in olfactory bulb. With the right nostril occluded for a 2-day exposure, Mn accumulated only in the left olfactory bulb. Solubilization of the Mn oxide UFPs was < 1.5% per day. CONCLUSIONS: We conclude that the olfactory neuronal pathway is efficient for translocating inhaled Mn oxide as solid UFPs to the central nervous system and that this can result in inflammatory changes. We suggest that despite differences between human and rodent olfactory systems, this pathway is relevant in humans

Neurobehavioral Functions, Serum Prolactin and Plasma Renin Activity of Manganese-Exposed Workers

Objective of this study was to assess effects of manganese (Mn) exposure on 56 workers employed in a Mn welding workshop of a machine building factory in Taiyuan (Shanxi Province, P.R. China) for a mean period of 16.1 years. The mean air Mn level in the workshop was 138.4 μg/m3. Neurobehavioral Core Test Battery (NCTB), including the Profile of Mood States (POMS), was performed. Blood pressure (BP) increase following immediate stand-up (BP-IS), serum prolactin (PRL) and plasma renin activity (PRA) in supine position were also determined. Most of the NCTB scores of the Mn-exposed workers were lower than those of the controls, while the POMS scores were higher, indicating a Mn-induced impairment of neurophysiological functions and a deflection of mood towards negative emotion states. PRL values of the Mn-exposed workers were higher than those of the controls. BP-IS of Mn-exposed workers was significantly lower than that of the controls. PRA of the same workers was augmented more than 200 %. In the Mn-exposed workers, the higher PRL values are possibly due to a reduced inhibitory effect on pituitary lactotrope cells by the tubero-infundibular dopamine system; the decreased BP-IS was referred to imbalance between the sympathetic and parasympathetic activities, whereas the higher basal PRA was thought to depend on neuroendocrine changes (including increased central sympathetic tone) and/or on a direct effect of Mn on renal juxta-glomerular cells. On the whole, this study demonstrates that occupational Mn exposure is responsible for neurobehavioral changes coexisting with alterations of neuroendocrine and humoral systems

Neurocognitive Effects in Welders Exposed to Aluminium: An Application of the NPC Test and NPC Ranking Methods

Aluminium exposure, Dependent rankings, Neurocognitive effects, Nonparametric combination, Permutation tests,

Repeated simultaneous cortical electrophysiological and behavioral recording in rats exposed to manganese-containing nanoparticles

Male Wistar rats wearing chronically implanted cortical electrodes were exposed to Mn-containing nanoparticles via the airways for 8 weeks following a 2-week pre-exposure period. The rats’ cortical electrical activity and open field motility was recorded simultaneously, in weekly repetitions. It was supposed that this technique can provide better insight in the development of Mn-induced CNS damage. Decreased motility (less distance covered, longer periods of immobility) and increased total power of cortical electrical activity developed in parallel in the first 4–5 weeks of treatment but showed little change afterwards. Both the behavioral and the electrophysiological effect were in fair correlation with the rats’ internal Mn exposure determined from brain samples. The results confirmed the non-linear dose- and time-dependence of Mn effects suggested by previous studies. Repeated simultaneous behavioral and electrophysiological recording during a longer treatment with neurotoxic metals (or other xenobiotics) seems to be a promising method