Trimethyltin-induced alterations in behavior are linked to changes in PSA-NCAM expression.
The neurotoxic heavy metal trimethyltin (TMT) primarily damages neurons of the hippocampus and limbic areas of the temporal lobe, and causes a dose-dependent decrease in the polysialated form of the neural cell adhesion molecule (PSA-NCAM) in the mouse hippocampus. In the current study, we attempted to associate deficits in spatial learning following TMT exposure at various stages in learning with changes in levels of NCAM-180 and PSA-NCAM in both the hippocampus and frontal cortex. Mice were treated with TMT either before or after training on a spatial learning paradigm and examined for changes in NCAM and PSA-NCAM 12h later. In the first set of experiments, male BALB/c mice were injected with TMT (2.25 mg/kg) or saline i.p. and tested 24-168 h later using hidden and visible versions of the water maze, as well as light avoidance and motor activity. Mice in both treated and control groups which demonstrated a significant improvement in water maze performance also showed an elevation in hippocampal PSA-NCAM at all time points examined. TMT exposure impaired spatial learning and blocked learning-induced elevations in PSA-NCAM expression 24-96 h post-treatment, but these deficits disappeared by 168 h post-treatment. Mice exposed to TMT during reconsolidation of spatial learning (after repeated water maze training) demonstrated a mild and transient difference in escape latency compared to saline exposed mice. TMT administration during this period did not result in the attenuation of PSA-NCAM expression observed when animals were exposed before training. These results confirm a specific role for PSA-NCAM in acquisition and consolidation of spatial memory.
Halladay
A K
AK
Joint Graduate Program in Toxicology, Rutgers University, Piscataway, NJ, USA.
Wilson
D T
DT
Wagner
G C
GC
Reuhl
K R
KR
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis*; D012794:Sialic Acids / Q000096:biosynthesis*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; D014298:Trimethyltin Compounds; C103469:polysialyl neural cell adhesion molecule; C046488:trimethyltin