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Table 5 Effects of Manganese (Mn) on different behavioral tasks

From: “Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

Experimental model Treatment Behavioral task Results Reference
Male Sprague-Dawley rats Neonate rats were orally exposed to MnCl2(0, 25, 50 mg/kg/day) between PND1-21 8-arm radial maze paradigm Mn-exposed males showed working memory impairment [149]
Young adult male Wistar rats One group was treated with 14.84 (low dose group), and another one with 59.36 (high dose group), mg/kg Mn given by gavage, 5 days a week for 10 weeks. 8-arm radial maze task MnCl2 treated groups showed, compared to control animals, a decrease in the average memory performance [170]
Male Wistar rats Single oral doses of MnCl2 (50 mg/kg) or chronic oral MnCl2 (20 or 50 mg/kg/ day) for 1 month Active avoidance
paradigm
Single dose induced decline of the memory acquisition of an avoidance reaction in response to unconditioned and conditioned stimuli. Chronic manganese poisoning also led to significant impairment of learning processes [168]
C. elegans 1 h Mn (10 or 25 mM) exposure on L1 larval stage Basal slowing response Mn-exposed worms had an impaired basal slowing response, indicating DAergic damage. This was reversed by SLC30A10 (a cell surface-localized Mn efflux transporter) expression in DAergic neurons [67]
C. elegans 30 min Mn (50 mM) exposure on L1 larval stage Dauer movement In WT dauer worms, the locomotion was increased in the presence of Mn, indicating DA signaling impairment [161]
Male and female Sprague-Dawley rats Pregnant females treated with Mn (2 mg/ml) in drinking water from the first day of pregnancy until PND20. MWM PND 21–25: Mn-exposed females displayed memory deficits in the probe trial
PND 56–60: Mn-exposed males performed significantly worse in the acquisition trial. Females exposed to Mn displayed deficits in learning and memory
[159]
Three-month-old male Wistar rats Intranasal 2-week-long MnCl2 (0.8 mg/kg body weight) MWM Spatial memory deficits [160]
Male Sprague-Dawley rats Intraperitoneal injection of MnCl2 15 mg/kg for 8, 12 or 18 weeks MWM Escaping latency and swimming distance of rats in the model groups increased, suggesting spatial learning and memory impairment [162]
Male Sprague Dawley rats Intraperitoneal injections of 0, 5, 10 and 20 mg/kg MnCl2 once daily, 5 days/ week for 18 weeks. MWM Mn impaired learning and memory as follow:
In 6 weeks at dose 20 mg/kg. In 12 weeks at doses 10 and 20 mg/kg. In 18 weeks at doses 5, 10 and 20 mg/kg
[163]
Male Sprague-Dawley rats (6 weeks of age) Intraperitoneal injections 15 mg/kg MnCl2 daily for 8 weeks. MWM The escape latency in the Morris water maze test was significantly longer in the rats injected with Mn indicating worsening in spatial memory [164]
Sprague-Dawley rats, 3-week- old Intraperitoneal injections (5, 10, 20 mg/kg MnSO4) 5 days a week for 24 weeks MWM Mn exposure decreased the spatial learning ability in a dose- and time- dependent manner [169]
Male Wistar rats Exposed intraperitoneally to MnCl2 at doses 5, 10 or 20 mg/kg/day from PND 8–12 Object and social recognition tasks PND 60–65: Rats exposed to the highest Mn dose failed to recognize a familiar object when replaced by a novel object as well as to recognize a familiar juvenile rat after a short period of time, indicating cognitive impairment [139]
Adult male M. fascicularis macaques, 5 to 6 years old Mn was administered as MnSO4 for 15 mg/kg/week for 5 weeks and then 20 mg /kg/week for the remainder of the study period (12 months) SOSS and
5-CSRT tasks
Deficits in performance of the SOSS task began to appear by the fourth month of Mn exposure but only became consistently significantly impaired beginning at the ninth month of Mn exposure. Performance on the 5-CSRT became significantly affected by the third month of Mn exposure [167]
Adult male M. fascicularis monkeys with 5 to 6 years old MnSO4 at doses 10–15 mg/kg/week over an exposure period
lasting 272 ± 17 days
Variable delayed response task Animals developed subtle deficits in spatial working memory and had modest decreases in spontaneous activity and manual dexterity [166]
Adult male M. fascicularis macaques, 5 to 6 years old MnSO4 at doses 15–20 mg/kg/week over an exposure period lasting 227.5 ± 17.3 days Variable delayed response task Animals developed mild deficits in spatial working memory, more significant deficits in non-spatial working memory and no deficits in reference memory [165]
  1. Abbreviations: 5-CSRT five choice serial reaction time, DA dopamine, MWM Morris water maze, PND post-natal day, SOSS self-ordered spatial search
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