Effects of Ethanol Exposure during the Third Trimester Equivalent on Neuron Number in Rat Hippocampus and Dentate Gyrus

West, John C; Hamre, Kristin; Cassell, Martin D.

doi:10.1111/j.1530-0277.1986.tb05070.x

Cited by 163 publications

(60 citation statements)

References 36 publications

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“…Although ethanol appears to affect proliferation in some populations [Miller, 1986], in many studies it has been shown to exert the most damaging effects in later periods, during stages of neuronal maturation and differentiation [Goodlett and Eilers, 1997;West et al, 1994West et al, , 1986. In addition, in the chick embryo, as noted earlier, we have found that ethanol applied during a period well after the completion of proliferation within this population (G10-15; motoneuron generation occurs from G2-5 [Hollyday and Hamburger, 1977]) also results in motoneuron loss [Bradley et al, 1997[Bradley et al, , 1999.…”

Section: B Asupporting

confidence: 49%

“…Such deficits have been described in a great many regions and structures of the developing mammalian brain and brainstem, including the cerebral cortex [Miller, 1986], hippocampus [Barnes and Walker, 1981;West et al, 1986], cerebellum [Hamre and West, 1993;Pierce et al, 1993;Goodlett and Eilers, 1997], substantia nigra [Shetty et al, 1993], red nucleus [Zajac et al, 1989], inferior olivary nucleus [Napper and West, 1995], basal ganglia [Heaton et al, 1996;Mattson et al, 1994], olfactory bulb [Bonthius and West, 1991;Bonthius et al, 1992], optic nerve [Ashwell and Zhang, 1994], corpus callosum [Riley et al, 1995], chief sensory trigeminal nucleus [Miller and Muller, 1988] and the oculomotor nucleus [Burrows et al, 1995]. Very little information is available concerning ethanol effects on neurological structures caudal to the brainstem, however.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal Ethanol Exposure Reduces Spinal Cord Motoneuron Number in the Fetal Rat but Does Not Affect GDNF Target Tissue Protein

Kidd²,

Bradley³

et al. 1999

Dev Neurosci

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Fetal rats were exposed throughout gestation to one of three diets: an ethanol-containing liquid diet, a liquid diet with the isocaloric substitution of sucrose for ethanol or a laboratory chow control diet. At postnatal day 1 (P1), the spinal cords were taken for analyses of motoneuron number and size. These analyses revealed a significant loss of motoneurons and a reduction of motoneuron size in the ethanol-exposed animals, compared to both sucrose and chow controls. Spinal cord length and ventral horn volume were not altered as a result of ethanol treatment, so the change in motoneuron number cannot be attributed to volumetric changes. The content of the motoneuron survival factor glial cell-line-derived neurotrophic factor (GDNF) was also assessed in the P1 limb motoneuron target tissue. This analysis was undertaken because GDNF is a potent survival factor for developing motoneurons and has been shown to protect this population from ethanol neurotoxicity. Thus, its depletion could contribute to motoneuron loss. These analyses, using the ELISA assay, did not detect reductions in GDNF in the ethanol-exposed animals. Therefore, alterations in other neurotrophic factors or ethanol neurotoxicity by other means appear to be responsible for the motoneuron loss. These results are consistent with earlier studies in the chick embryo, which also found reduced motoneuron numbers as a function of developmental ethanol exposure, and point again to the general lethality of ethanol to the developing nervous system.

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Section: B Asupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Prenatal Ethanol Exposure Reduces Spinal Cord Motoneuron Number in the Fetal Rat but Does Not Affect GDNF Target Tissue Protein

Kidd²,

Bradley³

et al. 1999

Dev Neurosci

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“…Details of alterations in CNS structure and function caused by ethanol exposure during development have been reported to occur in both humans and laboratory animals (e.g., Hammer and Scheibel, 1981;Riley et al, 1986;Streissguth, 1986;West et al, 1986;Miller and Muller, 1989;Miller and Potempa, 1990;Driscoll et al, 1990;Phillips and Krueger 1992;Pauli et al, 1995a;Dangata and Kaufman, 1997;Miki et al, 1999;Maier and West, 2001). Animal studies that have used the rat as a model have often carried out ethanol exposure during about the first 10 -14 postnatal days (PND) of life.…”

Section: Introductionmentioning

confidence: 97%

Effects of alcohol exposure during early life on neuron numbers in the rat hippocampus. I. Hilus neurons and granule cells

et al. 2003

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We previously showed that 16-day-old rats exposed to a relatively high dose of ethanol at 10-15 postnatal days of age have fewer neurons in the hilus region of the hippocampus compared with controls. Dentate gyrus granule cell numbers, however, showed no statistically significant changes attributable to the ethanol treatment. It is possible that some of the changes in brain morphology, brought about as a result of the exposure to ethanol during early life, may not be manifested until later in life. This question has been further addressed in an extension to our previous study. Wistar rats were exposed to a relatively high daily dose of ethanol on postnatal days 10-15 by placement in a chamber containing ethanol vapour, for 3 h/day. The blood ethanol concentration was found to be approximately 430 mg/dl at the end of the period of exposure. Groups of ethanol-treated (ET), separation control (SC), and mother-reared control (MRC) rats were anaesthetised and killed either at 16 or 30 days of age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle and the physical disector methods were used to estimate, respectively, the regional volumes and neuron cell numerical densities in the hilus and granule cell regions of the dentate gyrus. The total numbers of neurons in the hilus region and granule cell layer were computed from these estimates. It was found that 16-day-old animals had 398,000-441,000 granule cells, irrespective of group. The numbers of granule cells increased such that by 30 days of age, rats had 487,000-525,500 granule cells. However, there were no significant differences between ethanol-treated rats and their age-matched controls in granule cell numbers. In contrast, ethanol-treated rats had slightly but significantly fewer neurons in the hilus region than did control animals at 16 days of age, but not at 30 days of age. Therefore, it appears that a short period of ethanol exposure during early life can have effects on neuron numbers of some hippocampal neurons, but not others. The effects on hilar neuron numbers, observed as a result of such short periods of ethanol treatment, appeared to be transitory.

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“…Most studies on the effects of alcohol on brain development have focused on the third-trimester model. For example, early studies from West and his colleagues used a third-trimester model in rats to demonstrate neuronal cell loss in the cerebellum, olfactory bulb, and hippocampus after alcohol exposure (12)(13)(14)(15)(16)(17). Rodent cell culture models and tumor-derived cell lines also have been used extensively to understand the effects of ethanol on neuronal survival and differentiation, i.e., events that occur during the third trimester.…”

Section: Effects Of Alcohol During Brain Growth and Developmentmentioning

confidence: 99%

Modeling the Impact of Alcohol on Cortical Development in a Dish: Strategies from Mapping Neural Stem Cell Fate

Miranda

Santillano

Camarillo

et al. 2008

Alcohol

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SummaryDuring the second trimester period, neuroepithelial stem cells give birth to millions of new neuroblasts, which migrate away from their germinal zones to populate the developing brain and terminally differentiate into neurons. During this period, large numbers of cells are also eliminated by programmed cell death. Therefore, the second trimester constitutes an important critical period for neuronal proliferation, migration, differentiation and apoptosis. Substantial evidence indicates that teratogens like ethanol can interfere with neuronal maturation. However, there is a paucity of good model systems to study early, second trimester events. In vivo models are inherently interpretatively complex because cell proliferation, migration, differentiation, and death mechanisms occur concurrently in regions like the cerebral cortex. This temporal overlap of multiple developmental critical periods makes it difficult to evaluate the relative vulnerability of any individual critical period. Our laboratory has elected to utilize fetal rodent cerebral corticalderived neurosphere cultures as an experimental model of the second-trimester ventricular neuroepithelium. This model has enabled us to use flow cytometric approaches to identify neuroepithelial stem cell and progenitor sub-populations and to show that ethanol accelerates the maturation of neural stem cells. We have also developed a simplified mitogen-withdrawal/matrixadhesion paradigm to model the exit of neuroepithelial cells from the ventricular zone towards the subventricular zone and cortical plate, and their maturation into multipolar neurons. We can treat neurosphere cultures with ethanol to mimic exposure during the period of neuroepithelial proliferation and by using the step-wise maturation model, ask questions about the impact of prior ethanol exposure on the subsequent maturation of neurons as they migrate and undergo terminal differentiation. The combination of neurosphere culture and stepwise maturation models will enable us to dissect out the contributions of specific developmental critical periods to the overall teratology of a drug of abuse like ethanol.

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Effects of Ethanol Exposure during the Third Trimester Equivalent on Neuron Number in Rat Hippocampus and Dentate Gyrus

Cited by 163 publications

References 36 publications

Prenatal Ethanol Exposure Reduces Spinal Cord Motoneuron Number in the Fetal Rat but Does Not Affect GDNF Target Tissue Protein

Prenatal Ethanol Exposure Reduces Spinal Cord Motoneuron Number in the Fetal Rat but Does Not Affect GDNF Target Tissue Protein

Effects of alcohol exposure during early life on neuron numbers in the rat hippocampus. I. Hilus neurons and granule cells

Modeling the Impact of Alcohol on Cortical Development in a Dish: Strategies from Mapping Neural Stem Cell Fate

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