Sex Related Differences in Rat’s Behavior and Brain Morphology After the Toxic Effect of Manganese

  • Tamar Bikashvili Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia
  • Tamar Lordkipanidze Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia
  • Lia Gelazonia Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia
  • Mariam Mikadze Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia
  • Nino Pochkhidze Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia
Keywords: manganese, rat, behavior, neurotoxicity, gender


Exposure to heavy metals is a common phenomenon, which is due to contaminated drinking water and industrial activities. The toxic effect of different forms of metals is not only related to the environment, but also related to the metabolism and detoxification mechanism of the organism. In order to explore the difference of manganese toxicity on male and female rats, we studied the impact of manganese compounds on rat behavior and brain morphology. Four-week-old Wistar rats with body weight between 80-120g (n=42, including 21 males and 21 females) were studied. Wistar rats were assigned to four groups: rats in control groups (male, female) were given regular water, while rats in other groups drank water with final manganese concentration of 15 mg/ml (male, female) for three months. To study exploratory and anxiety behavior rats were tested in open field, home cage and elevated plus maze. To estimate learning and memory status multi-branched maze was used. The behavioral disturbance of male rats was more noticeable than that of female rats in the same group. It is found that excessive manganese ions also had more toxic effects on male animals than females. It was revealed that manganese poisoning increased Mn contents in the brains of both genders, caused slight damage of neurons, and produced notable gliosis. However, in hippocampus there were bioaccumulation differences between gender. Excess amount of manganese in the brain had a strong impact on learning processes. It was concluded that, under this experimental design, Mn exposure causes metal deposition in CNS. The effect of this dose of manganese was gender-dependent and males had more pronounced behavioral damage compared to females, but females had an indication of motor damage. Gender differences in neuron morphology were not due to differential accumulation of Mn in brain regions. But the effect of manganese exposure was not similar in all observed brain regions (Motor Cortex, Prefrontal Cortex, Hippocampus-CA1, CA3 area and Dentate Gyrus).    


. O'Neal S. L., and Zheng W. Manganese toxicity upon overexposure: a decade in review. Current Environmental Health Reports. 2015; 2:315-328.

. Leonhard M. J., Chang E. T., Loccisano A. E., and Garry M. R. A systematic literature review of epidemiologic studies of developmental manganese exposure and neurodevelopmental outcomes. Toxicology. 2019; 420:46-65.

. Vollet K., Haynes E. N., and Dietrich K. N. Manganese exposure and cognition across the lifespan: contemporary review and argument for biphasic dose-response health effects. Current Environmental Health Reports .2016; 3:392-404.

. Guilarte T. R. Manganese neurotoxicity: new perspectives from behavioral, neuroimaging, and neuropathological studies in humans and non-human primates. Frontiers in Aging Neuroscience. 2013; 5:23.

. Balachandran R.C., Mukhopadhyay S., McBride D., Veevers J., Harrison F.E., Aschner M., Haynes E. N., and Bowman A.B. Brain manganese and the balance between essential roles and neurotoxicity. Journal of Biological Chemistry. 2020; 295(19):6312-6329.

. Rechtman E, Curtin P, Papazaharias DM, Renzetti S, Cagna G, Peli M, Levin-Schwartz Y, Placidi D, Smith DR, Lucchini RG, Wright RO, Horton MK. Sex-specific associations between co-exposure to multiple metals and visuospatial learning in early adolescence. Translational Psychiatry. 2020; 10:358.

. Madison J.L., Wegrzynowicz M., Aschner M., and Bowman A.B. Gender and manganese exposure interactions on mouse striatal neuron morphology. Neurotoxicology. 2011; 32(6):896-906.

. Schmitz C.R.R., Eichwald T., Flores M.V.B., Varela K.G., Mantovani A., Steffani J.A., Glaser V., Carvalho D., Remor A.P. Sex differences in subacute manganese intoxication: Oxidative parameters and metal deposition in peripheral organs of adult Wistar rats. Regulatory Toxicology and Pharmacology. 2019; 104:98-107.

. Oulhote Y., Mergler D., and Bouchard M. F. Sex- and age-differences in blood manganese levels in the U.S. general population: national health and nutrition examination survey 2011–2012. Environ Health. 2014; 13:87.

How to Cite
Tamar Bikashvili, Tamar Lordkipanidze, Lia Gelazonia, Mariam Mikadze, & Nino Pochkhidze. (2021). Sex Related Differences in Rat’s Behavior and Brain Morphology After the Toxic Effect of Manganese. International Journal of Applied Sciences: Current and Future Research Trends , 12(1), 19-32. Retrieved from