Caffeine and its dimethylxanthines and fetal cerebral development in rat

Effects of Maternal Caffeine Ingestion on the Perinatal Cerebrum

“…Many studies have been per formed on the effects of maternal caffeine ingestion on various reproductive, terato genic and developmental characteristics in rats [1,2] and humans [3,4], However, even now, whether or not and if so how maternal caffeine ingestion is a risk factor in the de velopment of offspring is a matter of discus sion. In a previous study we demonstrated the adverse effect of maternal caffeine inges tion on the fetal cerebrum in the rat, which may be associated with the decreased appar ent volume of distribution of caffeine in ma ternal plasma and the high caffeine content of fetal cerebrum [5][6][7]. In the present study a low level of maternal caffeine consumption was maintained and an attempt was made to elucidate the factors related to cerebral func tion.…”

“…To our knowledge, these phenomena were not recognized in previously docu mented studies. In our pregnant rats, 0.04 and 0.02% caffeine intakes were calculated to correspond approximately to less than 50 and 25 mg caffcine/kg body weight/day, re spectively, because the consumed volume measurements were rough [5,6], When the maternal and fetal caffeine levels in the morning on gestational day 21 in the present study were compared with those in the eve ning on gestational day 20 in the previous study [5], it was considered that these levels were maintained at least during middle to late pregnancy. Therefore, an adverse effect of maternal caffeine on the fetal cerebrum is possible with a level of 1.5-3.0 jig caffeine/ml in maternal plasma, this concentra tion coinciding with that found on random plasma caffeine measurement in 600 adult outpatients [10].…”

“…The experimental procedures used for the prepa ration of fetal models were essentially as described previously [5,6], Virgin female albino rats of the Wistar strain were divided into caffeine (1,3,7-trimethylxanthine; Wako Chemical Industries Ltd., Osaka, Ja pan) and control groups, receiving 0.04% caffeine (C) or 0.02 % caffeine (c) via drinking water, and drinking water only (W), respectively. The groups are desig nated as follows; W or c before mating -W or C (c) during pregnancy.…”

“…The concentrations of caffeine, theophylline, paraxanthine and theobromine were determined essen tially by the methods of Bonati et al [8] and Tse et al [9], with minor modifications as described previously [6,7). Briefly, after extraction with chloroforrmisopropyl alcohol (75:25, v/v), a sample in 0.005 M sodium acetate buffer, pH 5, was injected into a 10-pm pBondapak C|8 column, with a mobile phase of 0.005 M sodium acetate buffer (pH 5):mcthyl alcohol:acetonitrile:tetrahydrofuran (92.5:3:2.8:1.7, v/v).…”

Association study in Alzheimer’s disease of single nucleotide polymorphisms implicated with coffee consumption

“…The hydrophobic nature of caffeine allows its rapid absorption through all biological membranes, rendering it is rapidly absorbed into the bloodstream and through the blood-brain barrier 23 . In vitro studies, showed that caffeine increases basal synaptic transmission, but does not affect LTP, at the same synapses 24 .…”