Cognitive and neuroanatomical effects of triethyltin in developing rats: role of age of exposure.
Long-Evans rat pups were injected i.p. on postnatal day 5 (PND5) or 12 with 0, 3, or 5 mg/kg triethyltin sulfate (TET) and then tested on T-maze delayed alternation on PND21 or 28. Delayed alternation learning was impaired on PND21 and 28 in pups given 5 mg/kg TET. Pups given 5 mg/kg TET on PND5 were more impaired on delayed alternation than pups given 5 mg/kg TET on PND12. Pups given 3 mg/kg TET on PND5 or 12 were unimpaired at either age of testing. On the day following training, pups were sacrificed for histological assessment employing Nissl- or immunohistochemical staining for glial fibrillary acidic protein (GFAP), a putative marker of gliosis. Pups given 5 mg/kg TET on PND5 showed increases in GFAP immunoreactivity (IR) in subiculum, amygdala, hippocampus, piriform cortex, and entorhinal cortex with concomitant decreases in Nissl-stained cells in these regions. Pups given 5 mg/kg TET on PND12 showed increases in GFAP IR in piriform cortex, amygdala and dorsal hippocampus with concomitant decreases in Nissl-stained cells in these regions. Exposure to 3 mg/kg TET on PND5 and PND12 produced a mild increase in GFAP IR in piriform cortex and amygdala but no discernible loss of Nissl-staining in these respective regions. TET-induced behavioral deficits appear related to damage of structural correlates of the human temporal lobe and not piriform cortical pathology. These results demonstrate that the day of exposure greatly influences the magnitude of the cognitive deficits and neuropathology associated with exposure to TET. There appears to be a critical period during postnatal development for the developmental neurotoxicity of this compound.
Freeman
J H
JH
Department of Psychology, University of North Carolina at Chapel Hill 27599-3270.
Barone
S
S
Stanton
M E
ME
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D001923:Brain Chemistry / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D013037:Spatial Behavior / Q000187:drug effects*; D014267:Triethyltin Compounds / Q000633:toxicity*
D005904:Glial Fibrillary Acidic Protein; D014267:Triethyltin Compounds; C031575:triethyltin