Pharmacokinetics of acute tryptophan depletion using a gelatin-based protein in male and female Wistar rats |
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Authors: | L A W Jans C K J Lieben L T Smits A Blokland |
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Institution: | (1) Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18, 1090 Vienna, Austria;(2) Eleanor Roosevelt Institute, University of Denver, Denver, CO, USA;(3) Division for Laboratory Animal Science and Genetics, Medical University of Vienna, Himberg, Austria;(4) Institute for Physiology, Veterinary University Vienna, Vienna, Austria; |
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Abstract: | In a previous publication we observed aberrant levels of the human reduced folate carrier (hRFC) in cortex from fetal Down
syndrome (DS) subjects. Immunoreactivity for hRFC was increased as the only chromosome 21 gene product studied. We, therefore,
analyzed mice transgenic for hRFC (TghRFC1) and wild-type (WT) mice for cognitive functions, behavior and in an observational
neurological battery (FOB). Cognitive functions were evaluated by the Morris water maze (MWM), the open field (OF) was used
for exploratory behavior, locomotor activity and anxiety-related behavior. The elevated plus maze (EPM) was used to confirm
findings in the OF testing anxiety-related behavior and the rota rod (RR) to evaluate motor function. In the MWM TghRFC1 mice
performed significantly worse (P < 0.0003) on the probe trial than WT mice. In the FOB visual placing was significantly reduced inTghRFC1 mice. In the OF
TghRFC1 mice crossed twice as often (P < 0.029) and in the EPM individuals from this group showed a reduced number of exits from the closed arm (P < 0.044) compared to WT mice. TghRFC1 mice showed impaired performance on the RR, spending one-fourth of the time of WT on
the revolving rod (P < 0.0003). Cognitive impairment is an obligatory symptom of DS and this deficiency corresponds to findings in the MWM of
mice transgenic for hRFC. Findings of visual placing and failure on the RR may reflect impaired motor performance including
muscular hypotonia in DS subjects. Increased crossings in the OF may indicate modulated anxiety-related behavior observed
in patients with DS. |
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