Metabolic Brain Disease

, Volume 25, Issue 3, pp 339–354 | Cite as

Structural and functional alterations in the hippocampus due to hypothyroidism

  • Christos Koromilas
  • Charis Liapi
  • Kleopatra H. Schulpis
  • Konstantinos Kalafatakis
  • Apostolos Zarros
  • Stylianos Tsakiris
Review Article


Thyroid hormones (THs) exert a broad spectrum of effects on the central nervous system (CNS). Hypothyroidism, especially during CNS development, can lead to structural and functional changes (mostly resulting in mental retardation). The hippocampus is considered as one of the most important CNS structures, while the investigation and understanding of its direct and indirect interactions with the THs could provide crucial information on the neurobiological basis of the (frequently-faced in clinical practice) hypothyroidism-induced mental retardation and neurobehavioral dysfunction. THs-deficiency during the fetal and/or the neonatal period produces deleterious effects for neural growth and development (such as reduced synaptic connectivity, delayed myelination, disturbed neuronal migration, deranged axonal projections, decreased synaptogenesis and alterations in neurotransmitters’ levels). On the other hand, the adult-onset thyroid dysfunction is usually associated with neurological and behavioural abnormalities. In both cases, genomic and proteomic changes seem to occur. The aim of this review is to provide an up-to-date synopsis of the available knowledge regarding the aforementioned alterations that take place in the hippocampus due to fetal-, neonatal- or adult-onset hypothyroidism.


Hippocampus Hypothyroidism Brain Thyroid hormones Thyroxine Triiodothyronine Mental retardation Neurobehavioral dysfunction Structural changes Functional changes Genomics Proteomics 



thyroid hormones


central nervous system






thyroid hormone


TH receptors


terminal deoxynucleotidyl transferase dUTP nick end labeling


N-methyl-D-aspartic acid


subventricular zone


subgranular zone


Disabled-1 (gene)


neural cell adhesion molecule


nerve growth factor








calcium ion


long-term potentiation


nerve growth factor-induced gene A


immediate early genes


integrated optical density


growth associated protein of 43 kDa




collapsin response mediated protein


cell adhesion molecule


muscarinic receptor 1


mitogen-activated protein kinase




choline acetyltransferase


polychlorinated biphenyl




sodium/potassium adenosine-triphosphatase




adenosine triphosphate


adenosine receptor 1


ecto-nucleoside triphosphate diphosphohydrolase 3


adenosine monophosphate


adenosine diphosphate


prostaglandin D2


prostaglandin H2


excitatory postsynaptic potential


gamma-aminobutyric acid


extracellular signal-regulated kinases


c-Jun N-terminal kinases


p38 mitogen-activated protein kinases






chlorine ion



The authors wish to express their appreciation to the medical students Marianna Almpani, Ioanna Loupasi and Ioannis-Angelos Trantos for their assistance in manuscript preparation. The authors are grateful to Mr Ioannis Mantzikos (BSc, PGDip, MSc) for his assistance in manuscript improvement.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Christos Koromilas
    • 1
  • Charis Liapi
    • 1
  • Kleopatra H. Schulpis
    • 2
  • Konstantinos Kalafatakis
    • 1
  • Apostolos Zarros
    • 1
    • 3
  • Stylianos Tsakiris
    • 3
  1. 1.Department of Pharmacology, Medical SchoolNational & Kapodistrian University of AthensAthensGreece
  2. 2.Institute of Child Health“Aghia Sophia” Children’s HospitalAthensGreece
  3. 3.Department of Physiology, Medical SchoolNational & Kapodistrian University of AthensAthensGreece

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