Effects of neonatal alcohol exposure on vasoactive intestinal polypeptide neurons in the rat suprachiasmatic nucleus.

Neonatal alcohol exposure produces long-term changes in the suprachiasmatic nucleus (SCN) that are presumably responsible for disturbances in the light-dark regulation of circadian behavior in adult rats, including the pattern of photoentrainment, rate of re-entrainment to shifted light-dark cycles, and phase-shifting responses to light. Because SCN neurons containing vasoactive intestinal polypeptide (VIP) receive direct photic input via the retinohypothalamic tract and thus play an important role in the circadian regulation of the SCN clock mechanism by light, the present study examined the long-term effects of neonatal alcohol exposure on VIP neuronal populations within the SCN of adult rats. Male Sprague-Dawley rat pups were exposed to alcohol (EtOH; 3.

Alcohol exposure on postnatal day 5 induces Purkinje cell loss and evidence of Purkinje cell degradation in lobule I of rat cerebellum.

The reduction in neuron number in specific brain regions is one of the most destructive aspects of alcohol-induced developmental brain injury, and its occurrence depends on the timing, pattern, and dose of maternal alcohol consumption during pregnancy. The purpose of this investigation was to quantify the dose-response aspect of Purkinje cell loss and rapid cellular degradation indicative of Purkinje cell loss following a single alcohol exposure on postnatal day 5 in lobule I, a lobule that has been shown to be vulnerable to alcohol-induced injury during cerebellar development. Fluoro-Jade B was used to identify Purkinje cell degeneration in 2-h intervals during the first 24h following the single alcohol exposure.

Neonatal alcohol exposure differentially alters clock gene oscillations within the suprachiasmatic nucleus, cerebellum, and liver of adult rats.

Background: In rats, alcohol exposure during the period of rapid brain growth produces long-term changes in the free-running period, photoentrainment and phase-shifting responses of the circadian rhythm in wheel-running behavior. To determine whether these alterations in circadian behavior are associated with permanent damage to the circadian timekeeping mechanism or reconfiguration of its molecular components, we examined the long-term effects of neonatal alcohol exposure on clock gene rhythms in the pacemaker located in the suprachiasmatic nucleus (SCN) and in other brain or peripheral tissues of adult rats.

Methods: Artificially reared male rat pups were exposed to alcohol (4.

Temporal vulnerability of fetal cerebellar Purkinje cells to chronic binge alcohol exposure: ovine model.

Background: Human magnetic resonance imaging (MRI) and autopsy studies reveal abnormal cerebellar development in children who had been exposed to alcohol prenatally, independent of the exposure period. Animal studies conducted utilizing the rat model similarly demonstrate a broad period of vulnerability, albeit the third trimester-equivalent of human brain development is reported to be the most vulnerable period, and the first trimester-equivalent exposure produces cerebellar Purkinje cell loss only at high doses of alcohol. However, in the rat model, all 3 trimester-equivalents do not occur prenatally, requiring the assumption that intrauterine environment, placenta, maternal interactions, and parturition do not play an important role in mediating the damage.

Chronic ethanol increases fetal cerebral blood flow specific to the ethanol-sensitive cerebellum under normoxaemic, hypercapnic and acidaemic conditions: ovine model.

Cerebral hypoxia has been proposed as a mechanism by which prenatal ethanol exposure causes fetal alcohol spectrum disorder (FASD) in children, but no study had tested this hypothesis using a chronic exposure model that mimicks a common human exposure pattern. Pregnant sheep were exposed to ethanol, 0.75 or 1.

Uptake and elimination of ethanol by young zebrafish embryos.

Among animal models being explored to understand ethanol-induced teratogenesis, the zebrafish (Danio rerio) is attracting attention because its embryonic development is well characterized and readily visualized. Despite the potential of the zebrafish embryo in research on developmental anomalies produced by ethanol exposure, little is known about the relationship between embryonic ethanol content and the nature/severity of ethanol-mediated deficits. Here, using gas chromatography and radiometry of labeled ethanol carbon, we examine accumulation and clearance of ethanol by dechorionated zebrafish embryos during blastulation/gastrulation.

Binge alcohol exposure during all three trimesters alters bone strength and growth in fetal sheep.

Women who drink while pregnant are at a high risk of giving birth to children with neurodevelopmental disorders. Heavy consumption of alcohol during pregnancy is also known to be deleterious to fetal bone growth in both humans and laboratory animals. However, nothing is known regarding the effect of maternal moderate and heavy alcohol binging on fetal and maternal bone strength.

Nicotine decreases blood alcohol concentrations in adult rats: a phenomenon potentially related to gastric function.

Background: In spite of the fact that drinking and smoking often occur together, little is known about the pharmacokinetic interaction between alcohol and nicotine. Previous research in neonatal rats demonstrated that nicotine reduces blood alcohol concentrations (BACs) if alcohol and nicotine are administered simultaneously. However, it is unclear whether such a phenomenon can be observed in adult subjects, given the fact that there is an ontogenetic difference in alcohol metabolism.

Long-term effects of neonatal alcohol exposure on photic reentrainment and phase-shifting responses of the activity rhythm in adult rats.

In rats, neonatal alcohol (EtOH) exposure coinciding with the period of rapid brain growth produces structural damage in some brain regions that often persists into adulthood and thus may have long-term consequences in the neural regulation of behavior. Because recent findings indicate that the circadian clock located in the rat suprachiasmatic nucleus is vulnerable to alcohol-induced insults during development, the present study examined the long-term effects of neonatal alcohol exposure on the photic regulation of circadian behavior in adult rats. Rat pups were exposed to alcohol (3.

Neonatal alcohol exposure permanently disrupts the circadian properties and photic entrainment of the activity rhythm in adult rats.

Background: Alcohol exposure during the period of rapid brain development produces structural damage in different brain regions, including the suprachiasmatic nucleus (SCN), that may have permanent neurobehavioral consequences. Thus, this study examined the long-term effects of neonatal alcohol exposure on circadian behavioral activity in adult rats.

Methods: Artificially reared Sprague-Dawley rat pups were exposed to alcohol (EtOH; 4.

Fetal alcohol syndrome: an assessment of the field.

Fetal exposure to alcohol is the major known cause of mental retardation in the Western world. For more than half of the 20th century, the placenta was widely believed to be an effective barrier against environmental agents. The discovery that offspring of pregnant women who were exposed to German measles or administered thalidomide were often malformed raised awareness that teratogens could be any environmental agent, including viruses and drugs, that caused abnormal development.

Alcohol and the developing brain: neuroanatomical studies.

One of the distinguishing features of prenatal alcohol exposure is impaired cognitive and behavioral function resulting from damage to the central nervous system. Information available from the small number of autopsied cases in humans indicates that the offspring of mothers who abused alcohol during pregnancy have various neuroanatomical alterations ranging from gross reductions in brain size to cellular alterations. Recent neuroimaging technology provides the most powerful tool for assessing the neurotoxic effects of fetal alcohol exposure in living organisms and for exploring the relationship between behavioral dysfunction and brain damage at the regional level.

Long-term alcohol exposure prior to conception results in lower fetal body weights.

Background: It is well known that alcohol consumption during pregnancy can result in lower birth weight babies but many women stop consuming alcohol prior to conception as a part of pregnancy planning. The purpose of this study was to determine whether alcohol consumption prior to conception may also have an effect on fetal development.

Methods: Male and female C57BL/6J mice at 4, 6, or 8 weeks of age received either a single administration of alcohol (3.

Developmental alcohol exposure alters light-induced phase shifts of the circadian activity rhythm in rats.

Background: Developmental alcohol (EtOH) exposure produces long-term changes in the photic regulation of rat circadian behavior. Because entrainment of circadian rhythms to 24-hr light/dark cycles is mediated by phase shifting or resetting the clock mechanism, we examined whether developmental EtOH exposure also alters the phase-shifting effects of light pulses on the rat activity rhythm.

Methods: Artificially reared Sprague-Dawley rat pups were exposed to EtOH (4.

Developmental alcohol exposure disrupts circadian regulation of BDNF in the rat suprachiasmatic nucleus.

In rats, damage to neuronal populations in some brain regions occurs in response to neonatal alcohol exposure coinciding with the period of rapid brain growth. These alcohol-induced defects in brain development may persist into adulthood and thus have long-term implications for the functional characteristics of damaged neuronal populations. The present study examined the effects of neonatal alcohol exposure on endogenous rhythmicity of the circadian clock located in the rat suprachiasmatic nucleus (SCN).

Alcohol and nutritional control treatments during neurogenesis in rat brain reduce total neuron number in locus coeruleus, but not in cerebellum or inferior olive.

Although a significant amount of progress has been made during the past two decades in determining the effects of alcohol on brain development, there is still a gap in the literature in terms of when the neurons in the brain are more or less vulnerable to the deleterious effects of alcohol. Using a rat model system, we examined the effect of alcohol on the development of three brain regions after exposure to alcohol only during the period of neurogenesis of each specific region. Our working hypothesis was that all three regions would be equally vulnerable to alcohol-induced reductions in neuron number after exposure during neurogenesis.

Blood ethanol concentration profiles: a comparison between rats and mice.

It is important to select an appropriate model system for studies examining the mechanisms of ethanol-induced injury. The most common model systems use either mice or rats with ethanol administered by means of intragastric gavage or intraperitoneal injection, yet few studies have compared directly the blood ethanol concentration (BEC) profiles that result from each of these model systems. In the current study, Sprague-Dawley rats and C57BL/6J mice were given ethanol by means of intragastric gavage or intraperitoneal injection at 40 days of age.

Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the developing rat hippocampus.

Children with fetal alcohol syndrome (FAS) display altered performance in tasks of learning and memory, behaviours thought to be associated with the hippocampus. Altered hippocampal structure has been reported in some FAS children; therefore, a rat model system was used to determine whether the size and numbers of pyramidal cells in regions CA1 and CA3 of the hippocampal formation and granule cells in the dentate gyrus were altered by alcohol exposure during different periods of development. Rat pups were exposed to alcohol in utero during the second trimester-equivalent (E10-20), the first two trimesters-equivalent (E1-20), during the time of hippocampal pyramidal cell neurogenesis (E16-20), part of the third trimester-equivalent (P4-9), and all three trimesters-equivalent (E1-20+P4-9).

Fetal and maternal thyroid hormone responses to ethanol exposure during the third trimester equivalent of gestation in sheep.

Background: Abnormal thyroid hormone system function in the mother or fetus during pregnancy can result in brain defects, some of which resemble those found in children with fetal alcohol syndrome. It has been hypothesized that ethanol may act to mediate alcohol-related birth defects in part by altering thyroid hormone system function. We investigated whether a binge pattern of maternal ethanol consumption over the last trimester equivalent of gestation in sheep results in an alteration in fetal or maternal thyroid function.