title: Therapeutic motor training increases parallel fiber synapse number per Purkinje neuron in cerebellar cortex of rats given postnatal binge alcohol exposure: preliminary report.
abstract: Because therapeutic approaches to fetal alcohol effects in humans have been rare, this study explored the rehabilitative effect of complex motor training on an animal model of binge drinking in the third trimester of human pregnancy. Neonatal alcohol exposure induces significant and permanent reductions in Purkinje and granule cell number accompanied by impaired motor behavior in rats. The purpose of this study was to determine: (1) whether the motor skill impairment caused by exposure to alcohol in the early postnatal period could be ameliorated by the learning of a set of complex motor tasks that had been demonstrated to cause synaptogenesis in the cerebellar cortex; and (2) the extent to which cerebellar neurons in alcohol-exposed (AE) rats exhibit synaptic plasticity. The AE group was given 4.5 g/kg/day of ethanol from postnatal days 4 to 9 via an artificial rearing procedure producing a mean peak blood alcohol level of 257 mg/dl. Control groups consisted of a gastrostomy control (GC) group, that received an isocaloric mixture of maltose/dextrin instead of ethanol, and a suckle control (SC) group, that was reared normally by dams. At approximately 6 months of age, animals from the three groups were assigned either to a rehabilitation condition (RC; that received 10 days of training on the motor tasks) or to an inactive condition (IC; where rats stayed in isolation in their cages). Although SC rats were significantly faster to complete the course in the first 5 days of training, there were no differences in ability to perform among animals from all three groups-SC, GC, and AE--at the end of the training period. Unbiased stereological techniques were used to obtain estimates of the number of parallel fiber synapses/Purkinje cell within the cerebellar paramedian lobule. Results showed that the RC rats from the SC and AE groups had significantly more synapses/Purkinje cell than corresponding IC animals. These data demonstrate that rehabilitative intervention (complex motor training) can improve motor performance impaired by postnatal alcohol exposure and that surviving Purkinje neurons retain the capacity for synaptic plasticity.
authors.affiliation: Beckman Institute, University of Illinois, Urbana-Champaign 61801, USA.
authors.forename: A Y
authors.initials: AY
authors.lastname: Klintsova
authors.forename: J T
authors.initials: JT
authors.lastname: Matthews
authors.forename: C R
authors.initials: CR
authors.lastname: Goodlett
authors.forename: R M
authors.initials: RM
authors.lastname: Napper
authors.forename: W T
authors.initials: WT
authors.lastname: Greenough
mesh_terms: D000435:Alcoholic Intoxication / Q000473:pathology*; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002525:Cerebellar Cortex / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D008297:Male; D009048:Motor Skills / Q000187:drug effects*; D009412:Nerve Fibers / Q000187:drug effects* / Q000473:pathology; D011214:Practice, Psychological; D011247:Pregnancy; D011689:Purkinje Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D013569:Synapses / Q000187:drug effects* / Q000473:pathology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D000431:Ethanol