Caffeine consumption during pregnancy accelerates the development of cognitive deficits in offspring in a model of tauopathy

Abstract

20Psychoactive drugs used during pregnancy can affect the development of the brain of offspring, 21 directly triggering neurological disorders or increasing the risk for their occurrence. Caffeine is 22 the most widely consumed psychoactive drug, including during pregnancy. In Wild type mice, 23 early life exposure to caffeine renders offspring more susceptible to seizures. Here, we tested 24 the long-term consequences of early life exposure to caffeine in THY-Tau22 transgenic mice, 25 a model of Alzheimer's disease-like Tau pathology. Caffeine exposed mutant offspring 26 developed cognitive earlier than water treated mutants. Electrophysiological recordings of 27 hippocampal CA1 pyramidal cells in vitro revealed that early life exposure to caffeine changed 28 the way the glutamatergic and GABAergic drives were modified by the Tau pathology. We 29 conclude that early-life exposure to caffeine affects the Tau phenotype and we suggest that 30 caffeine exposure during pregnancy may constitute a risk-factor for early onset of Alzheimer's 31 disease-like pathology. 32 33 34 6 gluconate, 10.0 mM HEPES, 15.0 mM sodium gluconate, 0.2 mM EGTA, 4.0 mM NaCl, pH 126 7.2. After 20 minutes recovery in a preincubation solution (110 mM Choline chloride, 2.5 mM 127KCl, 1.25 mM NaH2PO4, 10 mM MgCl2, 0.5 mM CaCl2, 25 mM NaHCO3, 10 mM D-glucose, 128 5 mM sodium pyruvate equilibrated with 5% CO2 in 95% O2 at room temperature), slices were 129 perfused for at least one hour with aCSF containing 126.0 mM NaCl, 25.0 mM NaHCO3, 10.0 130 mM D-glucose, 3.5 mM KCl, 2.0 mM CaCl2, 1.3 mM MgCl2.6H2O and 1.2 mM NaH2PO4 131 equilibrated with 5% CO2 in 95% O2 at room temperature and transferred to a chamber 132 containing the same aCSF, kept at a temperature between 33 ºC and 35 ºC. Cells were recorded 133 under visual control (Nikon FN1 microscope -Scientifica Patch Star manipulators) with an 134

In utero exposure of green coffee extract alters rat fetal neurodevelopment in a dose dependent manner

“…Ultrastructural It has been postulated that psychoactive substances consumed during pregnancy may have deleterious effects on fetal neurodevelopment (Salisbury et al, 2009). Previous studies have ascertained that prenatal administration of caffeine slowed down the migration of the GABAergic neurons, increased neuronal loss and delayed postnatal development in rat pups (Silva et al, 2013), increasing susceptibility to epilepsy and hyperactivity, in addition to cognitive deficits in the offspring (Vesoulis et al, 2016;Fazeli et al, 2017;Zappettini et al, 2019).…”

“…Brain development occurs in early life and any disturbances or alterations in the development process, either anatomically or functionally, can have a detrimental effect on the developing fetus (Lenroot and Giedd, 2006;Zappettini et al, 2019). This disturbance can affect cell migration and proliferation, synapse formation, and cortical connectivity eventually resulting in improper neural development and leading to behavioral abnormalities later in life (Thompson et al, 2009;Guerrini and Dobyns, 2014).…”

“…Great caution and concern should be taken during pregnancy regarding the different chemicals that pass freely through the placenta to the fetus imposing great risk (van der Hoeven et al, 2017). In utero exposure to stimulants during pregnancy can alter the brain development of fetuses which may induce the development of many neural and even psychiatric disorders (Zappettini et al, 2019).…”

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

“…Compared to control offspring, formation and activity of cortical networks was found to be impaired in offspring of caffeine-exposed mouse dams. In another study that sought to mimic human consumption patterns with the use of 0.30 mg/ml caffeine in drinking water, Zappettini, et al [52] were careful to parallel human exposure before and during pregnancy until full-term birth, taking account of both the time span of caffeine exposure and amount of caffeine consumed. Electrophysiological recordings of hippocampal CA1 pyramidal cells in vitro revealed caffeinerelated changes likely to increase the risk for early onset of dementia-associated pathology.…”