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Updated: May 18, 2026

Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Effect of intranasal manganese administration on neurotransmission and spatial learning in rats
Kamilla Blecharz-Klin1, Agnieszka Piechal, Ilona Joniec-Maciejak
1Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmieście 26/28, 00-927 Warsaw, Poland.
Abstract:
The effect of intranasal manganese chloride (MnCl(2)·4H(2)O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2weeks MnCl(2)·4H(2)O at two doses the following: 0.2mg/kg b.w. (Mn0.2) or 0.8mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions.
Insights
Intranasal manganese chloride exposure in rats impaired spatial memory and cognitive performance. This cognitive deficit was linked to significant changes in brain monoamine neurotransmitter levels and metabolism.
Area of Science:
- Neuroscience
- Toxicology
- Behavioral Science
Background:
- Manganese is an essential element, but excessive exposure can lead to neurotoxicity.
- Intranasal administration offers a direct route to the brain, bypassing the blood-brain barrier.
- Understanding the neurobehavioral effects of intranasal manganese is crucial for assessing potential risks.
Purpose of the Study:
- To investigate the impact of intranasal manganese chloride exposure on spatial learning, memory, and motor activity in adult rats.
- To determine the effects of manganese on neurotransmitter levels in key brain regions.
Main Methods:
- Adult male Wistar rats were exposed intranasally to two doses of manganese chloride (0.2mg/kg or 0.8mg/kg) or a control solution for two weeks.
- Behavioral assessment was conducted using the Morris water maze task to evaluate spatial learning and memory.
- Neurotransmitter and metabolite concentrations in the prefrontal cortex, hippocampus, and striatum were analyzed using High-Performance Liquid Chromatography (HPLC).
Main Results:
- While acquisition in the Morris water maze was not significantly affected, rats exposed to manganese exhibited significant spatial memory deficits during the probe trial.
- HPLC analysis revealed significant alterations in monoamine and metabolite levels in the prefrontal cortex, hippocampus, and striatum of manganese-exposed rats compared to controls.
- Negative correlations were observed between spatial memory performance and neurotransmitter turnover, suggesting a link between manganese-induced cognitive impairment and changes in serotonergic, noradrenergic, and dopaminergic systems.
Conclusions:
- Intranasal manganese exposure can impair spatial memory and cognitive function in adult rats.
- These cognitive deficits are associated with significant changes in the tissue levels and metabolism of monoamines in critical brain regions.
- The findings highlight the potential neurotoxic effects of intranasally administered manganese on cognitive processes and neurotransmitter systems.

