Gender influence on manganese induced depression-like behavior and Mn and Fe deposition in different regions of CNS and excretory organs in intraperitoneally exposed rats

Manganese (Mn) is an essential metal for mammals. It can modulate the action of endogenous substances, as neurotransmitters, but in excess also can trigger known neurotoxic effects. Many studies have been conducted assessing Mn neurotoxicity. However, Mn bioaccumulation in different brain tissues and behavior effects involving gender-specific studies are conflicted in the literature. Therefore, the aim of this work was to compare Mn effects, after 30 days of intraperitoneal treatment, in male and female rats, submitted to forced swim and open field tests. After that, were evaluated Mn and Fe tissue levels in CNS, liver, and kidneys. Wistar rats were divided into saline, Mn 1 mg/kg, Mn 5 mg/kg, and imipramine (as forced swim control). Then, animals were euthanized by anesthesia overdose followed by decapitation and the collected tissue were striatum, hippocampus, brainstem, cortex, cerebellum, hepatic tissue, and renal tissue. Mn and Fe were determined by ICP-MS. There was a dose-dependent effect on accumulation of Mn in the cerebellum and brainstem to the dosage of 5 mg/kg. In hippocampus there were bioaccumulation differences between gender and dose, and an increase of Fe in the groups exposed to Mn. Excess metals in the brain dissected has a strong influence on memory and learning processes and suggests pro-depressive effects, possibly triggered by the reduction of monoamines due to excessive metal bioaccumulation. It was concluded that, under this experimental design, Mn exposure cause metal deposition on dissected CNS, liver and kidney. There an effect at lower doses that was gender-dependent and males had more pronounced behavioral damage compared to females, although with increasing dose, females had an indication of motor damage.