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Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat

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Abstract

Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na+,K+- and Mg2+-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent approaches towards the experimental simulation of congenital and early-age-occurring hypothyroidism.

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Fig. 1
Fig. 2

Notes

  1. Insufficiency of thyroid hormones (THs) during neurodevelopment could be a result of congenital hypothyroidism or maternal hypothyroidism due to iodine-deficiency, autoimmune thyroiditis, previous thyroidectomy, drug treatments/abuse, TH-disrupting xenobiotics, etc.

Abbreviations

AChE:

acetylcholinesterase

ATPases:

adenosine-triphosphatases

CNS:

central nervous system

FC:

frontal cortex

Hi:

hippocampus

Na+,K+-ATPase:

sodium/potassium adenosine-triphosphatase

Mg2+-ATPase:

magnesium adenosine-triphosphatase

PTU:

propylthiouracil

T4 :

thyroxine

T3 :

3,5,3′-triiodothyronine

THs:

thyroid hormones

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Acknowledgments

This study was funded by the National and Kapodistrian University of Athens. Dr Christos Koromilas has received financial support by a 4-year “Antonios Papadakis” PhD scholarship (01/09/2008-31/08/2012). The authors wish to acknowledge their appreciation to Ms Vaso Gkanti and Dr 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

    Christos Koromilas, Alexios Bimpis & Charis Liapi

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

    Christos Koromilas, Stylianos Tsakiris, Konstantinos Kalafatakis, Apostolos Zarros, Vasileios Stolakis, Despoina Kimpizi, Alexios Bimpis & Anastasia Tsagianni

  3. Henry Wellcome Laboratories for Integrative Neuroscience & Endocrinology, School of Clinical Sciences, Faculty of Medicine & Dentistry, University of Bristol, Bristol, UK

    Konstantinos Kalafatakis

  4. Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

    Apostolos Zarros

  5. St. Mary’s Hospital, Imperial College Healthcare NHS Trust, London, England, UK

    Alexios Bimpis

Authors
  1. Christos Koromilas
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  2. Stylianos Tsakiris
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  3. Konstantinos Kalafatakis
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  4. Apostolos Zarros
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  5. Vasileios Stolakis
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  6. Despoina Kimpizi
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  7. Alexios Bimpis
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  8. Anastasia Tsagianni
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  9. Charis Liapi
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Corresponding author

Correspondence to Stylianos Tsakiris.

Additional information

Konstantinos Kalafatakis and Apostolos Zarros are authors with equal contribution to the study

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Koromilas, C., Tsakiris, S., Kalafatakis, K. et al. Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat. Metab Brain Dis 30, 241–246 (2015). https://doi.org/10.1007/s11011-014-9581-9

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  • DOI: https://doi.org/10.1007/s11011-014-9581-9

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