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Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner

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Abstract

The experimental simulation of conditions falling within “the fetal alcohol spectrum disorder” (FASD) requires the maternal exposure to ethanol (EtOH) during crucial neurodevelopmental periods; EtOH has been linked to a number of neurotoxic effects on the fetus, which are dependent upon the extent and the magnitude of the maternal exposure to EtOH and for which very little is known with regard to the exact mechanism(s) involved. The current study has examined the effects of moderate maternal exposure to EtOH (10 % v/v in the drinking water) throughout gestation, or gestation and lactation, on crucial 21-day-old offspring Wistar rat brain parameters, such as the activities of acetylcholinesterase (AChE) and two adenosine triphosphatases (Na+,K+-ATPase and Mg2+-ATPase), in major offspring CNS regions (frontal cortex, hippocampus, hypothalamus, cerebellum and pons). The implemented experimental setting has provided a comparative view of the neurotoxic effects of maternal exposure to EtOH between gestation alone and a wider exposure timeframe that better covers the human third trimester-matching CNS neurodevelopment period (gestation and lactation), and has revealed a CNS region-specific susceptibility of the examined crucial neurochemical parameters to the EtOH exposure schemes attempted. Amongst these parameters, of particular importance is the recorded extensive stimulation of Na+,K+-ATPase in the frontal cortex of the EtOH-exposed offspring that seems to be a result of the deleterious effect of EtOH during gestation. Although this stimulation could be inversely related to the observed inhibition of AChE in the same CNS region, its dependency upon the EtOH-induced modulation of other systems of neurotransmission cannot be excluded and must be further clarified in future experimental attempts aiming to simulate and to shed more light on the milder forms of the FASD-related pathophysiology.

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Notes

  1. offspring growth retardation has been linked to maternal malnutrition rather than foetal exposure to EtOH per se (Norton and Kotkoskie 1991; Ponnappa and Rubin 2000).

  2. the administration of EtOH in a controlled / forced manner (in contrast to that of diluting it in the drinking water) is certainly a more accurate method of monitoring / quantifying the maternal exposure to EtOH; it is more representative of clinical reality (with regard to dosing) compared with our approach of the constant offering of EtOH-supplemented water, but it is also more stressful for both the dam and the offspring.

  3. it should be noted that between P7 and P21, the rat septal and the hippocampal ChAT activities undergo a statistically-significant increase that is reported to be approximately 5- and 7-fold of those at P7, respectively (Swanson et al. 1995).

  4. by lubrol WX or phospholipase A (Marques and Guerri 1988).

  5. as determined by the non-synaptic plasma membrane ratio of phosphatic acid, phosphatidylinositol or phosphatidylserine against phosphatidylcholine or phosphatidylethanolamine (for more details, see Sun et al. 1984).

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Acknowledgments

The authors wish to acknowledge their appreciation to Drs Alexios Bimpis and Hussam Al-Humadi for their assistance.

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Authors and Affiliations

  1. Laboratory of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Vasileios Stolakis & Charis Liapi

  2. Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, GR-11527, Athens, Greece

    Vasileios Stolakis, Apostolos Zarros, Konstantina Kalopita, Vassilios Memtsas, John Botis, Anastasia Tsagianni, Despoina Kimpizi & Stylianos Tsakiris

  3. Research Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, UK

    Apostolos Zarros

  4. Ninewells Hospital & Medical School, College of Medicine, Dentistry & Nursing, University of Dundee, Dundee, UK

    Vassilios Memtsas

  5. Department of Pathology, Panarcadic General Hospital, Tripolis, Greece

    Alexios Varatsos

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  1. Vasileios Stolakis
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  2. Charis Liapi
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Correspondence to Charis Liapi or Stylianos Tsakiris.

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Stolakis, V., Liapi, C., Zarros, A. et al. Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner. Metab Brain Dis 30, 1467–1477 (2015). https://doi.org/10.1007/s11011-015-9730-9

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