Adenosine Receptor Antagonists Including Caffeine Alter Fetal Brain Development in Mice

Abstract

pregnancy.longitudinal prospective human studies will be needed to evaluate the consequences of caffeine consumption during effects of adenosine receptor antagonists including caffeine on brain development in humans. Retrospective and neuronal types as well as impaired memory on certain types of memory tests. This study raises questions about the that adult offspring of pregnant mice treated with adenosine receptor antagonists had reduced numbers of certain antagonists were more susceptible to seizures when exposed to a seizure-inducing agent. They further demonstrated into target regions. They then showed that 1-week-old offspring of pregnant mice treated with adenosine receptor delayed the migration of specific populations of neurons during brain maturation, resulting in their delayed insertion They found that caffeine or an adenosine receptor antagonist that specifically blocks type 2A adenosine receptors added caffeine to the drinking water of female mice throughout pregnancy and lactation. Monique Esclapez, 1,2 † Christophe Bernard 1,2 * † Consumption of certain substances during pregnancy can interfere with brain development, leading to deleterious long-term neurological and cognitive impairments in offspring. To test whether modulators of adenosine receptors affect neural development, we exposed mouse dams to a subtype-selective adenosine type 2A receptor (A 2A R) antagonist or to caffeine, a naturally occurring adenosine receptor antagonist, during pregnancy and lactation. We observed delayed migration and insertion of g-aminobutyric acid (GABA) neurons into the hippocampal circuitry during the first postnatal week in offspring of dams treated with the A 2A R antagonist or caffeine. This was associated with increased neuronal network excitability and increased susceptibility to seizures in response to a seizure-inducing agent. Adult offspring of mouse dams exposed to A 2A R antagonists during pregnancy and lactation displayed loss of hippocampal GABA neurons and some cognitive deficits. These results demonstrate that exposure to A 2A R antagonists including caffeine during pregnancy and lactation in rodents may have adverse effects on the neural development of their offspring.

Caffeine acts through neuronal adenosine A 2A receptors to prevent mood and memory dysfunction triggered by chronic stress

“…Prophylactic studies with caffeine or KW6002 were done using previously validated doses (14,40). Mice were divided into two groups: a drug-free group drinking water or vehicle and a treated group drinking either 1 g/L caffeine (Sigma), starting 3 wk before CUS, or KW6002 (istradefylline; 3 mg/kg, dissolved in 0.5% nitrocellulose), synthesized as described previously (41), starting 4 d before CUS.…”

“…Anhedonic-like behavior was evaluated with the sucrose (1.2%) preference test (44) by measuring the intake of sucrose solution versus water intake at the end of a 16-h test period (12-h dark phase plus 4-h light phase) or with the splash test by measuring grooming bouts (head washing and nose/face and body grooming) over 5 min after a 10% sucrose solution was squirted on the dorsal coat (45). Social recognition memory was evaluated as previously described (39), and spatial memory was evaluated using an object-displacement test (40), a reference memory version of the Morris water maze (46), and a two-trials Y-maze test in which mice first explored the maze for 8 min while one arm was blocked and explored it again 2 h later for 8 min with all three arms accessible (14). Behavioral experiments were conducted between 10:00 AM and 5:00 PM in a sound-attenuated room under low-intensity light and were monitored by two researchers who were unaware of phenotypes or drug treatments.…”

Chemical Composition, Antioxidant and Antibacterial Activity of Tunisian Date Palm Seed

“…Date seed presented an interesting antioxidant capacity to scavenging DPPH free radicals and it seems to be used in food as an important antioxidant source. For example, caffeine is the active ingredient found in coffee beans (Coffea), showing biological activity in the treatment of central nervous system (CNS) disorders [23][24].…”

Caffeine Intake during Pregnancy: What Are the Real Evidences?

“…Caffeine intake is negatively associated with gestational changes in animals, such as lower rates of fertilization and embryonic implantation, low birth and placental weight, greater number of stillbirths, increased expression of apoptotic markers and altered placental and bone formation [9,27,[40][41][42][43][44][45][46] ( Table 1).…”

“…Elmazar and colleagues [42] induced caffeine consumption in albino female mice intraperitoneally and orally, and described increased circulating corticosterone and cleft palate in litters, although no detection of reduced utero-placental or placental-fetal blood flow were reported at 14 GD. Silva and colleagues [43], exposing female mice to oral doses of 0.3 g/liter of caffeine (diluted in water), suggested that caffeine exposure by mouse pups during gestation and lactation had deleterious effects on neuronal development, hyper excitable hippocampus, susceptibility to seizures and cognitive deficits that could remain even in adult life. Serapiao-Moraes and colleagues [44] using C57BL/6 pregnant mice, with daily subcutaneous caffeine doses of 20 mg/kg, reported negative outcomes in adult offspring from treated mothers.…”