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Effects of phenytoin administered to newborn mice: motor behavior and brain development
252
1997NBTS ABSTRACTS
isotretinoin: continuum.
the subtle
end of the
Embryonic exposure to isotretinoin (I-E) produces a continuum of outcomes: death, malformation, reduced IQ, learning disability, and normality. At 5 years of age, non-retarded, I-E children show strengths in language-based abilities and weaknesses in visual-spatial & organizational abilities (Adams and Lammer, 1995). Here we report the longitudinal performance at age 10 of non-retarded I-E children and unexposed controls (all IQs > 80) on the Rey Osterreith Complex This task requires drawing Figure. a complex geometric design, and examines structural accuracy, organization, and errors. I-E children obtained significantly lower scores on all endpoints than did the unexposed control children. This suggests neural dysfunction in pathways which subserve the processing, encoding, and/or graphomotor reproduction of visual information: a subtle manifestation of I-E teratogenesis. Supported by NIH: ROl-HD29510.
NBTS
41
HATTA, T.l)*, H. OHMORIZ), K. YAMASHITAz,* and M. YASUDA2)*, ‘)Institute of Health Sciences, and 2)Department of Anatomy, Hiroshima University School of Medicine. Effects of phenvtoin administered to newborn mice: motor behavior and brain develonment. Ohmori et al. (1992) re orted that phenytoin (PHT) has developmenta P neurotoxicity on the cerebellum in mouse neonates. We examined correlation between behavioral and brain development in PHT-treated mice. PHT, suspended in sesame oil, was administered by gavage at doses of 10, 17.5, 35 and 70 mg/kg b.w. to newborn Jcl:ICR mice once a day on postnatal day (PD) 24 (day of birth = PDO). With video recordin we evaluated the following motor behaviora 5 development on PD5-20; quadruped stance on PD5-9, quadruped locomotion on PD5-11, swimming on PD6-14, dynamic postural adjustments on PD5-12, and complex locomotor shills on PD15-20. Ataxic
movement was evident in the 35 and 70 mg/kg PHT groups on the measurement of stance or locomotion on PD5. Hypotonicity was observed in the PHT treated group on measurement of stance, locomotion, swimming, righting reflex and negative geotaxis on PD5-10. We dissected brains into three parts; the cerebellum, brain stem and cerebrum on PD5, 7, 10, 14, or 21 and weighed each. Weight reduction of the cerebellum in the PHT groups, especially in the 35 and 70 mg/kg, was more distinct, compared with that of brain stem and cerebrum. It is suggested that cerebellar development was inhibited by PHT. Impairment of body balance and decreased muscle tone can be explained as a result of the poor cerebellar development. (Supported by a grant from the Epilepsy Research Foundation, Japan.) NBTS
42
c~sTENSEN,* HD., C.L. GONZALEZ,* JD. STEWART,* and W.F. RAY-BURN,Depts of Obstetrics & Gynecol~ and Phannacol~/roxicol~. university ofOklahoma Health Sciences Center, Oklahorm City, OK. Effect of repeating administration of antenatal betamethasone on cognition in mice offspring. The objective of this placebo-controlled investigation was to measure the effect of two different antenatal multidosing regimens of betamethasone on the long-term cognition of CD-l mice offspring. Treatment consisted of four doses, given either daily on day 13-l 6 of a 19 day gestation or twice daily on 14-l 5, using either a therapeutic dose of betamethasone (0.1 mg SC)or normal saline. Three offspring per gender from ten litters of each treatment group underwent cognitive tasks as juveniles and as adults. Data were compared using ANOVA or X2-square testing. Functional trends remained constant for the four treatmentgroups when performing the following tasks: juvenile runway with adult memoty; adult Morris maze with the platform either placed above or below the water or removed; adult straight water runway; adult Biel maze in both the forced and unforced decision directions. A lack of difference between the two betamethasone and the two placebo groups was found for each task. This finding for each task persisted after controlling for gender. Conclusion: Antenatal exposure to repeated administration of betamethasone did not impact on the offsprings’ cognitive responsiveness.
Supported by: J.W. Records Perinatal Research Fund.
1997NBTS ABSTRACTS
isotretinoin: continuum.
the subtle
end of the
Embryonic exposure to isotretinoin (I-E) produces a continuum of outcomes: death, malformation, reduced IQ, learning disability, and normality. At 5 years of age, non-retarded, I-E children show strengths in language-based abilities and weaknesses in visual-spatial & organizational abilities (Adams and Lammer, 1995). Here we report the longitudinal performance at age 10 of non-retarded I-E children and unexposed controls (all IQs > 80) on the Rey Osterreith Complex This task requires drawing Figure. a complex geometric design, and examines structural accuracy, organization, and errors. I-E children obtained significantly lower scores on all endpoints than did the unexposed control children. This suggests neural dysfunction in pathways which subserve the processing, encoding, and/or graphomotor reproduction of visual information: a subtle manifestation of I-E teratogenesis. Supported by NIH: ROl-HD29510.
NBTS
41
HATTA, T.l)*, H. OHMORIZ), K. YAMASHITAz,* and M. YASUDA2)*, ‘)Institute of Health Sciences, and 2)Department of Anatomy, Hiroshima University School of Medicine. Effects of phenvtoin administered to newborn mice: motor behavior and brain develonment. Ohmori et al. (1992) re orted that phenytoin (PHT) has developmenta P neurotoxicity on the cerebellum in mouse neonates. We examined correlation between behavioral and brain development in PHT-treated mice. PHT, suspended in sesame oil, was administered by gavage at doses of 10, 17.5, 35 and 70 mg/kg b.w. to newborn Jcl:ICR mice once a day on postnatal day (PD) 24 (day of birth = PDO). With video recordin we evaluated the following motor behaviora 5 development on PD5-20; quadruped stance on PD5-9, quadruped locomotion on PD5-11, swimming on PD6-14, dynamic postural adjustments on PD5-12, and complex locomotor shills on PD15-20. Ataxic
movement was evident in the 35 and 70 mg/kg PHT groups on the measurement of stance or locomotion on PD5. Hypotonicity was observed in the PHT treated group on measurement of stance, locomotion, swimming, righting reflex and negative geotaxis on PD5-10. We dissected brains into three parts; the cerebellum, brain stem and cerebrum on PD5, 7, 10, 14, or 21 and weighed each. Weight reduction of the cerebellum in the PHT groups, especially in the 35 and 70 mg/kg, was more distinct, compared with that of brain stem and cerebrum. It is suggested that cerebellar development was inhibited by PHT. Impairment of body balance and decreased muscle tone can be explained as a result of the poor cerebellar development. (Supported by a grant from the Epilepsy Research Foundation, Japan.) NBTS
42
c~sTENSEN,* HD., C.L. GONZALEZ,* JD. STEWART,* and W.F. RAY-BURN,Depts of Obstetrics & Gynecol~ and Phannacol~/roxicol~. university ofOklahoma Health Sciences Center, Oklahorm City, OK. Effect of repeating administration of antenatal betamethasone on cognition in mice offspring. The objective of this placebo-controlled investigation was to measure the effect of two different antenatal multidosing regimens of betamethasone on the long-term cognition of CD-l mice offspring. Treatment consisted of four doses, given either daily on day 13-l 6 of a 19 day gestation or twice daily on 14-l 5, using either a therapeutic dose of betamethasone (0.1 mg SC)or normal saline. Three offspring per gender from ten litters of each treatment group underwent cognitive tasks as juveniles and as adults. Data were compared using ANOVA or X2-square testing. Functional trends remained constant for the four treatmentgroups when performing the following tasks: juvenile runway with adult memoty; adult Morris maze with the platform either placed above or below the water or removed; adult straight water runway; adult Biel maze in both the forced and unforced decision directions. A lack of difference between the two betamethasone and the two placebo groups was found for each task. This finding for each task persisted after controlling for gender. Conclusion: Antenatal exposure to repeated administration of betamethasone did not impact on the offsprings’ cognitive responsiveness.
Supported by: J.W. Records Perinatal Research Fund.