Prenatal caffeine intake differently affects synaptic proteins during fetal brain development

Abstract

Caffeine is the psychostimulant most consumed worldwide. However, little is known about its effects during fetal brain development. In this study, adult female Wistar rats received caffeine in drinking water (0.1, 0.3 and 1.0 g/L) during the active cycle in weekdays, two weeks before mating and throughout pregnancy. Cerebral cortex and hippocampus from embryonic stages 18 or 20 (E18 or E20, respectively) were collected for immunodetection of the following synaptic proteins: brain-derived neurotrophic factor (BDNF), TrkB receptor, Sonic Hedgehog (Shh), Growth Associated Protein 43 (GAP-43) and Synaptosomal-associated Protein 25 (SNAP-25). Besides, the estimation of NeuN-stained nuclei (mature neurons) and non-neuronal nuclei was verified in both brain regions and embryonic periods. Caffeine (1.0 g/L) decreased the body weight of embryos at E20. Cortical BDNF at E18 was decreased by caffeine (1.0 g/L), while it increased at E20, with no major effects on TrkB receptors. In the hippocampus, caffeine decreased TrkB receptor only at E18, with no effects on BDNF. Moderate and high doses of caffeine promoted an increase in Shh in both brain regions at E18, and in the hippocampus at E20. Caffeine (0.3g/L) decreased GAP-43 only in the hippocampus at E18. The NeuN-stained nuclei increased in the cortex at E20 by lower dose and in the hippocampus at E18 by moderate dose. Our data revealed that caffeine transitorily affect synaptic proteins during fetal brain development. The increased number of NeuN-stained nuclei by prenatal caffeine suggests a possible acceleration of the telencephalon maturation. Although some modifications in the synaptic proteins were transient, our data suggest that caffeine even in lower doses may alter the fetal brain development.

Kalirin is required for BDNF-TrkB stimulated neurite outgrowth and branching

“…Well before birth, hippocampal and cortical neurons in the brain express BDNF and TrkB (Behar et al, 1997; Mioranzza et al, 2014). Exogenous BDNF increases the number of primary dendrites in an activity dependent manner through TrkB in specific cortical layers (McAllister et al, 1997; McAllister et al, 1995).…”

Caffeine combined with sedative/anesthetic drugs triggers widespread neuroapoptosis in a mouse model of prematurity

“…Notably, exposure of immature brain cells to CAF or SADs reduces mRNA and protein levels of BDNF [6,24–26], and altered BDNF expression by CAF or SADs has been implicated in neuroapoptosis [27] and long-term neurodevelopmental impairment [25,28]. In addition, CAF [29] and SADs [27,28] have been shown to downregulate activity of the pro-survival Akt pathway.…”

Axonal elongation and dendritic branching is enhanced by adenosine A2A receptors activation in cerebral cortical neurons

“…Importantly also, caffeine actions do not result solely from A 2A R antagonism since caffeine is an antagonist of different adenosine receptor subtypes. However, several studies have indeed shown that gestational exposure to caffeine may alter the normal development of the brain with cognitive consequences to the adult brain (Juárez-Méndez et al 2006;Soellner et al 2009;Silva et al 2013;Mioranzza et al 2014), by delaying migration and insertion of GABAergic neurons into the hippocampal circuitry (Silva et al 2013), by decreasing either BDNF or TrkB receptor levels (Mioranzza et al 2014), by affecting the different adenosine receptors expression during neural Fig. 11 Adenosine A 2A Rs activation increases microtubule dynamics.…”