title: Manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic administration of MnCl₂: hippocampal signal enhancement without disruption of hippocampus-dependent behavior.
abstract: Manganese (Mn(2+))-enhanced magnetic resonance (MR) imaging (MEMRI) in rodents offers unique opportunities for the longitudinal study of hippocampal structure and function in parallel with cognitive testing. However, Mn(2+) is a potent toxin and there is evidence that it can interfere with neuronal function. Thus, apart from causing adverse peripheral side effects, Mn(2+) may disrupt the function of brain areas where it accumulates to produce signal enhancement and, thereby, Mn(2+) administration may confound cognitive testing. Here, we examined in male adult Lister hooded rats if a moderate systemic dose of MnCl₂ (200 μmol/kg; two intraperitoneal injections of 100 μmol/kg separated by 1 h) that produces hippocampal MR signal enhancement would disrupt hippocampal function. To this end, we used a delayed-matching-to-place (DMP) watermaze task, which requires rapid allocentric place learning and is highly sensitive to interference with hippocampal function. Tested on the DMP task 1 h and 24 h after MnCl₂ injection, rats did not show any impairment in indices of memory performance (latencies, search preference) or any sensorimotor effects. However, MnCl₂ injection caused acute peripheral effects (severe ataxia and erythema, i.e. redness of paws, ears, and nose) which subsided over 30 min. Additionally, rats injected with MnCl₂ showed reduced weight 1 day after injection and failed to reach the normal weight-growth curve of control rats within the 16 days monitored. Our results indicate that 200 μmol/kg MnCl₂ produces hippocampal MR signal enhancement without disrupting hippocampus-dependent behavior on a rapid place learning task, even though attention must be paid to peripheral side effects.
authors: Centre for Cognitive and Neural Systems (CCNS), School of Biomedical Sciences, University of Edinburgh, Edinburgh, UK.
authors: Stewart J
authors: SJ
authors: Jackson
authors: Rosalind
authors: R
authors: Hussey
authors: Maurits A
authors: MA
authors: Jansen
authors: Gavin D
authors: GD
authors: Merrifield
authors: Ian
authors: I
authors: Marshall
authors: Alasdair
authors: A
authors: MacLullich
authors: Joyce L W
authors: JL
authors: Yau
authors: Tobias
authors: T
authors: Bast
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D001931:Brain Mapping; D002712:Chlorides / Q000008:administration & dosage* / Q000009:adverse effects; D003287:Contrast Media / Q000008:administration & dosage; D004890:Erythema / Q000139:chemically induced; D006624:Hippocampus / Q000502:physiology*; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese; D017895:Manganese Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D018782:Maze Learning / Q000502:physiology*; D051381:Rats
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D008345:Manganese; C025340:manganese chloride