Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice

Abstract

Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on the developmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8 g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day28–45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers.

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway

“…Consensus is that fetal exposure to alcohol is harmful. Prenatal alcohol exposure may induce abnormal brain development as well as decrease the capacity for learning and memory [12, 13]. Similar to alcohol, anticonvulsants, sedatives (such as ketamine), or narcotics can pass through the placental barrier and for ketamine in particular, researches showed its ability to impair the capacity for learning and memory [14, 15].…”

Neonatal alcohol exposure reduces number of parvalbumin-positive interneurons in the medial prefrontal cortex and impairs passive avoidance acquisition in mice deficits not rescued from exercise

“…This perhaps suggests that there were still some motor deficits present. Moreover, recently Fish and colleagues (2016) failed to see any impact of an acute gestational alcohol exposure on the rotarod performance of C57BL/6J males. Therefore, it is possible that the impact of neonatal alcohol exposure on motor performance is a little less reliable in mice than it is in rats.…”

Prenatal alcohol exposure disrupts Shh pathway and primary cilia genes in the mouse neural tube

“…Open field data were analyzed as four separate 15-min epochs (i.e. min 0-15, min 16-30, min 31-45, and min 46-60), based on prior findings that the initial minutes of the open field test are most sensitive to developmental drug exposure (11, 31).…”

“…Alcohol exposure during gastrulation, the stage when the embryo first forms distinct cell layers (3 rd week in humans, embryonic day [E] 7 in mice), induces widespread cell death in the neuroectoderm (5), and subsequent diminished Sonic hedgehog (Shh) signaling as a pathogenic mechanism for gastrulation-stage alcohol exposure (6–10). Alcohol exposure during neurulation, as the neural tube forms and closes (∼4 th -5 th weeks in humans, E8-10 in mice), produces midline structural defects in brain regions such as the hypothalamus, ventricles, pituitary, and septal regions (11–14). However, while prenatal alcohol exposure during neurulation causes cell death in regions such as the rhombencephalon, alcohol-induced apoptosis is not as pronounced in the rostroventral neural tube (5), the portion of the neural tube that gives rise to ventral midline brain structures.…”