Prenatal exposure to moderate levels of ethanol can have long-lasting effects on hippocampal synaptic plasticity in adult offspring

Sutherland, Robert J.; McDonald, Robert J.; Savage, Daniel D.

doi:10.1002/(sici)1098-1063(1997)7:2<232::aid-hipo9>3.0.co;2-o

Cited by 121 publications

(62 citation statements)

References 39 publications

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“…These include volume reductions in the basal ganglia, cerebrum, and cerebellum, agenesis of the corpus collosum, reduced pyramidal cell density and cell numbers in hippocampal formation (Livy, Miller, Maier, & West, 2003), and reduced numbers of neurons and glia in the somatosensory cortex (Miller & Potempa, 1990). Moreover, prenatal alcohol exposure in rodents has been shown to alter neurotransmitter functioning, including decreased DA uptake, deficits in serotonin reuptake sites, reduced density of NMDA receptor agonist binding sites, altered DA synthesis, and altered behavioral responses to dopaminergic drugs (Druse et al, 1990;Hannigan & Pilati, 1991;Kim & Druse, 1996;Maier, Chen, & West, 1996;Sutherland, McDonald, & Savage, 1997). Our own work has found that prenatal alcohol exposure contributed to altered DA neurotransmitter function in the striatum depending on the gestational timing of the alcohol exposure (Schneider et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Sensory Processing Disorder in a Primate Model: Evidence From a Longitudinal Study of Prenatal Alcohol and Prenatal Stress Effects

et al. 2008

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Disrupted sensory processing, characterized by over-or underresponsiveness to environmental stimuli, has been reported in children with a variety of developmental disabilities. This study examined the effects of prenatal stress and moderate-level prenatal alcohol exposure on tactile sensitivity and its relationship to striatal dopamine system function in thirty-eight 5-to 7-year-old rhesus monkeys. The monkeys were from four experimental conditions: (a) prenatal alcohol exposed, (b) prenatal stress, (c) prenatal alcohol exposed + prenatal stress, and (d) sucrose controls. Increased D 2 receptor binding in the striatum, evaluated using positron emission tomography neuroimaging, was related to increased withdrawal (aversion) responses to repetitive tactile stimuli and reduced habituation across trials. Moreover, prenatal stress significantly increased overall withdrawal responses to repetitive tactile stimulation compared to no prenatal stress.Sensory processing disorders, characterized by under-or overresponsiveness to sensory stimulation that most individuals perceive as harmless (Ayres & Robbins, 1979) NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript estimated to occur in 5% of the general population (Ahn, Miller, Milberger, & McIntosh, 2004) and seem to pose a unique challenge for people with developmental disabilities (Baranek, 2002), including autism, attention deficit hyperactivity disorder (ADHD), fragile X syndrome, and other developmental disabilities (Ayres & Tickle, 1980;Baranek, 1999;Baranek & Berkson, 1994;Baranek, Foster, & Berkson, 1997;Cermak & Daunhauer, 1997;Grandin, 1992;Kinnealey, 1973;Larson, 1982;Mangeot et al., 2001;Miller et al., 1999). Understanding the neurobiological processes associated with sensory processing disruptions is important to developing appropriate preventative and intervention approaches.This study examined whether disrupted sensory processing occurs in monkeys as a result of prenatal exposure to alcohol and/or stress, and if so, whether it would be associated with dopamine functioning in the striatum assessed with positron emission tomography (PET) neuroimaging. We employed a primate model for these studies because in human studies causal conclusions are difficult to reach due to confounding variables. Even with the best statistical analyses it is difficult, if not impossible, to separate completely the effects of variables associated with alcohol use, such as psychological stress, tobacco use, or chaotic home life, from the effects of fetal alcohol exposure per se. Nonhuman primates also have the advantage of gestation characteristics and early development similar to the human, and their shorter life span makes longitudinal studies somewhat easier to conduct. Rhesus monkeys were used because of the large amount of available data on their behavior and development in laboratory settings (Harlow & Harlow, 1969;Suomi, 1997) A. Jean Ayres (1964), an occupational therapist and educational psychologist, coined the term "tactile defensiveness" t...

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Section: Discussionmentioning

confidence: 99%

Sensory Processing Disorder in a Primate Model: Evidence From a Longitudinal Study of Prenatal Alcohol and Prenatal Stress Effects

et al. 2008

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“…Current understanding of spatial memory deficits in children with FASDs is largely derived from an extensive animal literature showing that rats exposed to ethanol during early brain development had impaired place learning ability (Gianoulakis, 1990;Sutherland et al, 2000) and damage to the hippocampus (Klintsova et al, 2007;Livy et al, 2003), an area closely associated with spatial learning and recall and particularly vulnerable to alcohol exposure in animals and humans (Berman & Hannigan, 2000). In a study of three children who sustained early bilateral hippocampal damage due to hypoxic-ischemic brain injury, VarghaKhadem et al (1997) found significant impairments in delayed reproduction of a spatial arrangement using the Rey-Osterrieth Complex Figure task (ROCF) and poor everyday spatial memory using the parental report Everyday Memory Questionnaire (EMQ).…”

Section: Introductionmentioning

confidence: 99%

Effects of prenatal alcohol exposure on hippocampal volume, verbal learning, and verbal and spatial recall in late childhood

Willoughby

Sheard

Nash

et al. 2008

J Int Neuropsychol Soc

162

164

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Children with prenatal alcohol exposure (PAE) show deficits in verbal learning and spatial memory, as well as abnormal hippocampal development. The relationship between their memory and neuroanatomic impairments, however, has not been directly explored. Given that the hippocampus is integral for the synthesis and retrieval of learned information and is particularly vulnerable to the teratogenic effects of alcohol, we assessed whether reduced learning and recall abilities in children with fetal alcohol spectrum disorders (FASDs) are associated with abnormal hippocampal volumes. Nineteen children with FASDs and 18 typically developing controls aged 9 to 15 years were assessed for verbal learning and verbal and spatial recall and underwent structural magnetic resonance imaging. Images were analyzed for total intracranial volume and for right and left hippocampal volumes. Results revealed smaller left hippocampi and poorer verbal learning and verbal and spatial recall performance in children with FASDs than controls, as well as positive correlations between selective memory indices and hippocampal volumes only in the FASD group. Additionally, hippocampal volumes increased significantly with age in controls only, suggesting that PAE may be associated with long-term abnormalities in hippocampal development that may contribute to impaired verbal learning and verbal and spatial recall. (JINS, 2008(JINS, , 14, 1022(JINS, -1033

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“…Our previous studies of Sprague-Dawley rats using a 5% ethanol liquid diet paradigm as a model of moderate drinking during pregnancy indicated that prenatal ethanol-exposed offspring exhibit performance deficits on increasingly challenging memory tasks (Sutherland et al, 2000;Weeber et al, 2001). These memory impairments are, in part, linked to physiological alterations that diminish activity-dependent enhancement of synaptic neurotransmission in hippocampal formation of affected offspring (Sutherland et al, 1997;Savage et al, 1998). Furthermore, decreased positive allosteric modulation of dentate granule cell N-methyl-D-aspartate (NMDA) receptors (Costa et al, 2000) and mGluR 5 receptor-mediated potentiation of gluta-mate release from perforant path nerve terminals (Galindo et al, 2004) have been implicated as putative neurochemical mechanisms underlying fetal ethanol-induced deficits in synaptic plasticity and learning.…”

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confidence: 99%

Effects of the Cognition-Enhancing Agent ABT-239 on Fetal Ethanol-Induced Deficits in Dentate Gyrus Synaptic Plasticity

Varaschin¹,

Akers²,

Rosenberg³

et al. 2010

J Pharmacol Exp Ther

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Prenatal ethanol exposure causes deficits in hippocampal synaptic plasticity and learning. At present, there are no clinically effective pharmacotherapeutic interventions for these deficits. In this study, we examined whether the cognition-enhancing agent 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl) benzonitrile (ABT-239), a histamine H 3 receptor antagonist, could ameliorate fetal ethanol-induced long-term potentiation (LTP) deficits. Long-Evans rat dams consumed a mean of 2.82 g/kg ethanol during a 4-h period each day. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, offspring litter size, and birth weights were not different between ethanol-consuming and control groups. A stimulating electrode was implanted in the entorhinal cortical perforant path, and a recording electrode was implanted in the dorsal dentate gyrus of urethane-anesthetized adult male offspring. Baseline input/output responses were not affected either by prenatal ethanol exposure or by 1 mg/kg ABT-239 administered 2 h before data collection. No differences were observed between prenatal treatment groups when a 10-tetanus train protocol was used to elicit LTP. However, LTP elicited by 3 tetanizing trains was markedly impaired by prenatal ethanol exposure compared with control. This fetal ethanol-induced LTP deficit was reversed by ABT-239. In contrast, ABT-239 did not enhance LTP in control offspring using the 3-tetanus train protocol. These results suggest that histamine H 3 receptor antagonists may have utility for treating fetal ethanol-associated synaptic plasticity and learning deficits. Furthermore, the differential effect of ABT-239 in fetal alcohol offspring compared with controls raises questions about the impact of fetal ethanol exposure on histaminergic modulation of excitatory neurotransmission in affected offspring.Heavy or binge patterns of drinking during pregnancy can cause profound morphological and neurological aberrations in offspring called fetal alcohol syndrome (Lemoine et al., 1968;Jones and Smith, 1973). However, increasing evidence indicates that even moderate drinking during pregnancy can cause subtle, long-term behavioral and cognitive impairments in the absence of the birth defects associated with fetal alcohol syndrome (for review, see Kodituwakku, 2009). These behavioral deficits may not become apparent until the educational years (Streissguth et al., 1990;Jacobson et al., 1998;Hamilton et al., 2003) and may increase in severity as the child matures (Streissguth et al., 1994).The mechanisms by which prenatal ethanol exposure causes long-lasting impairments in learning and memory are not well understood. Our previous studies of Sprague-Dawley rats using a 5% ethanol liquid diet paradigm as a model of moderate drinking during pregnancy indicated that prenatal ethanol-exposed offspring exhibit performance deficits on increasingly challenging memory tasks (Sutherland et al., 2000;Weeber et al., 2001). These memory impairments are, in part...

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Prenatal exposure to moderate levels of ethanol can have long-lasting effects on hippocampal synaptic plasticity in adult offspring

Cited by 121 publications

References 39 publications

Sensory Processing Disorder in a Primate Model: Evidence From a Longitudinal Study of Prenatal Alcohol and Prenatal Stress Effects

Sensory Processing Disorder in a Primate Model: Evidence From a Longitudinal Study of Prenatal Alcohol and Prenatal Stress Effects

Effects of prenatal alcohol exposure on hippocampal volume, verbal learning, and verbal and spatial recall in late childhood

Effects of the Cognition-Enhancing Agent ABT-239 on Fetal Ethanol-Induced Deficits in Dentate Gyrus Synaptic Plasticity

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