Table 5.
Effects of Manganese (Mn) on different behavioral tasks
| 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] |
Abbreviations: 5-CSRT five choice serial reaction time, DA dopamine, MWM Morris water maze, PND post-natal day, SOSS self-ordered spatial search