Time-specific effects of ethanol exposure on cranial nerve nuclei: Gastrulation and neuronogenesis

Abstract

During the development of the central nervous system, neurons pass through critical periods or periods of vulnerability. We explored periods of vulnerability for cranial nerve nuclei by determining the effects of acute exposure to ethanol during development on the number of neurons in mature brainstem. Long-Evans rats were injected with 2.9 g ethanol/kg body weight on one day between gestational day (G) 7 and G13, inclusive. Two hours later, animals received a second injection of 1.45 g/kg. Controls were injected with equivalent volumes of saline. Brainstems of 31-day-old offspring were cryosectioned and stained with cresyl violet. Stereological methods were used to determine the volume and numerical density of neurons in three trigeminal sensory nuclei (the principal sensory nucleus of the trigeminal nerve, and the oral and interpolar subnuclei of the spinal trigeminal nuclear complex) and three motor nuclei (the trigeminal, facial, and hypoglossal nuclei). The numbers of neurons in most nuclei were lower following early (on G7 and/or G8) or later (on G12 and/or G13) exposure. Only the trigeminal interpolar nucleus was affected by neither early nor late ethanol exposure. Thus, prenatal exposure to ethanol affects the number of neurons in brainstem nuclei in a time-dependent manner. Windows of vulnerability coincide with gastrulation (G7/G8) and the period of neuronal generation (G12/G13).

Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling

“…The mouse had a peak Blood Alcohol Concentration (BAC) around 200–250 mg dl −1 within a half hour after an administration. This falls in a range between the consumption levels by social drinkers (60 mg dl −1 ) and those by chronic alcoholics (320–620 mg dl −1 )5657, and is also similar to that used in previous studies reporting pathological and molecular effects of fetal alcohol exposure5859. The human in vitro model used the same range of EtOH concentration (50 mM (230 mg dl −1 )), by which several aspects of FASD phenotypes have been shown to be induced in the mouse cerebral cortex in vitro 60.…”

Low and moderate prenatal ethanol exposures of mice during gastrulation or neurulation delays neurobehavioral development

“…Hypoplasia in these structures after treatment of mice on GD7 is related to increased programmed cell death in the embryonic ectoderm, specifically the anterior neural ridge, from which cortical and striatal progenitors arise (Dunty et al, 2001; Sulik, 2005; Kilburn et al, 2006). Additionally, ethanol treatment during gastrulation results in decreased numbers of neurons of trigeminal sensory nuclei in rats (Mooney and Miller, 2007), and in lower numbers of neurons in the trigeminal sensory nuclei and somatosensory cortex in macaques (Miller 2007). …”

“…Specifically, structural forebrain defects are seen in the olfactory bulbs, septal area, neostriatum, frontal cortex, corpus callosum, and hippocampus (Sulik et al, 1984; Schambra et al, 1990; Ashwell and Zhang, 1996; Sulik, 2005; Godin et al, 2010). Additionally, in a rat model, acute ethanol exposure during gastrulation results in a decreased number of neurons in two sensory trigeminal nuclei, and the trigeminal, facial and hypoglossal motor nuclei (Mooney and Miller, 2007). In contrast, acute ethanol exposure of mouse embryos during neurulation produces abnormalities in forebrain, cerebellum, cranial nerves and ganglia, and facial structures with features resembling the DiGeorge syndrome (Sulik et al, 1986; Kotch and Sulik, 1992a; Dunty et al, 2002; Sulik, 2005; Parnell et al, 2009).…”

Fetal ethanol exposure increases ethanol intake by making it smell and taste better

“…With specific regard to the chemical senses, the flavor components of ethanol also include the perception of oral irritation conveyed through the trigeminal system. Fetal ethanol exposure is known to reduce the number of trigeminal neurons in the brainstem nuclei (41). This observation, in turn, could be expected to reduce the number of stimulus channels important to the perception of oral irritation.…”