Prenatal Caffeine Damaged Learning and Memory in Rat Offspring Mediated by ARs/PKA/CREB/BDNF Pathway

Abstract

Prenatal exposure to caffeine can cause developmental problems.This study determined chronic influence of prenatal caffeine at relatively higher doses on cognitive functions in the rat offspring.Pregnant Sprague-Dawley rats (4-month-old) were exposed to caffeine (20 mg/kg, twice a day) for whole pregnancy from gestational day 4. Fetal and offspring body and brain weight was measured. Learning and memory were tested in adult offspring with Morris water maze. Learning and memory-related receptors were measured. The exposure to prenatal caffeine not only caused fetal growth restriction, but also showed long-term effects on learning and memory in the offspring. The caffeine offspring exhibited longer escape latency and path length in navigation testing. The number of passing the target was significantly reduced in those offspring. The expression of adenosine A1 and A2A receptors, nuclear PKA Cα, Cβ subunits, and pCREB were significantly increased in the fetal and neonatal brain, and suppressed in the hippocampus of the adult offspring. The expression of BDNF and TrkB were reduced regardless of various ages. The results suggest that intrauterine programming dysfunction of adenosine receptors and the down-stream of cAMP/PKA/pCREB system may play an important role in prenatal caffeine induced cognition disorders in the adult offspring.

The protective role of melatonin against the effects of different doses of caffeine on the fetus

“…Given that caffeine passes through the placenta barrier, it might disrupt the development of various tissues, including bone tissue (31,32). One study reported that the weight of newborns in caffeine-treated groups was lower than in the control group (33). Caffeine during pregnancy could disturb development.…”

“…It was showed that caffeine may pass through the placenta and may cause possible growth retardation in the fetus (4,5). Accordingly, it was reported that caffeine could reduce the development of fetal rats and might cause adverse pregnancy effects (6)(7)(8).…”

Kaempferide prevents cognitive decline via attenuation of oxidative stress and enhancement of brain‐derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element‐binding signaling pathway

“…BDNF exerts its promoting effect mainly by binding to TrkB and the transcription factor cyclic adenosine monophosphate (cAMP) response element‐binding protein 1 (CREB1; Li et al, ; Liu et al, ). CREB is a widespread and constitutively expressed transcription factor that has been implicated in long‐lasting synaptic plasticity underlying learning and memory (Ko et al, ).…”

Maternal caffeine consumption and childhood behavioural and neurocognitive development: A focused narrative review

“…With the caveat that the translation of caffeine dosing in animal studies to human consumption patterns is complex and approximate, a dose of 0.30 mg/ml in drinking water was estimated by Silva, et al [48] to produce plasma concentrations of caffeine in rat dams comparable to that found in the blood of humans drinking 3-4 cups of coffee per day. On the other hand, Li, et al [49] estimated the same dose (0.30 mg/ml) of caffeine in drinking water to be comparable to the human consumption of about 2 cups of coffee per day. Thus, bearing in mind the approximate nature of such estimates, the Grimm and Frieder [41] "low" dose of 0.15 mg/ml and possibly the "medium" dose of 0.30 mg/ ml, could be considered comparable to reputed "moderate" and "safe" levels of exposure during human pregnancy.…”

“…Electrophysiological recordings of hippocampal CA1 pyramidal cells in vitro revealed caffeinerelated changes likely to increase the risk for early onset of dementia-associated pathology. In addition, Li et al [49] reported that expression of adenosine A 1 and A 2A receptors was impaired in fetal and neonatal brain among offspring of rat dams exposed to 20 mg/kg caffeine (compared to saline) administered twice daily via subcutaneous injection. The same study also reported that learning and memory were impaired in adult offspring exposed to caffeine in utero.…”