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Structural and functional alterations in the hippocampus due to hypothyroidism

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Abstract

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.

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Abbreviations

THs:

thyroid hormones

CNS:

central nervous system

T4 :

thyroxine

T3 :

3,5,3'-triiodothyronine

TH:

thyroid hormone

TRs:

TH receptors

TUNEL:

terminal deoxynucleotidyl transferase dUTP nick end labeling

NMDA:

N-methyl-D-aspartic acid

SVZ:

subventricular zone

SGZ:

subgranular zone

Dab1:

Disabled-1 (gene)

NCAM:

neural cell adhesion molecule

NGF:

nerve growth factor

NT-3:

neurotrophin-3

BrdU:

bromodeoxyuridine

RC3:

neurogranin

Ca2+ :

calcium ion

LTP:

long-term potentiation

NGFI-A:

nerve growth factor-induced gene A

IEGs:

immediate early genes

IOD:

integrated optical density

GAP-43:

growth associated protein of 43 kDa

Sema3F:

semaphorin-3F

CRMP:

collapsin response mediated protein

CAM:

cell adhesion molecule

M1:

muscarinic receptor 1

MAPK:

mitogen-activated protein kinase

PTU:

propylthiouracil

ChAT:

choline acetyltransferase

PCB:

polychlorinated biphenyl

AChE:

acetylcholinesterase

Na+,K+-ATPase:

sodium/potassium adenosine-triphosphatase

ACh:

acetylcholine

ATP:

adenosine triphosphate

A1:

adenosine receptor 1

NTPDase3:

ecto-nucleoside triphosphate diphosphohydrolase 3

AMP:

adenosine monophosphate

ADP:

adenosine diphosphate

PGD2 :

prostaglandin D2

PGH2 :

prostaglandin H2

EPSP:

excitatory postsynaptic potential

GABA:

gamma-aminobutyric acid

ERKs:

extracellular signal-regulated kinases

JNKs:

c-Jun N-terminal kinases

p38MAPKs:

p38 mitogen-activated protein kinases

PV:

parvalbumin

PV-IR:

PV-immunoreactivity

Cl- :

chlorine ion

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Acknowledgements

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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Authors and Affiliations

  1. Department of Pharmacology, Medical School, National & Kapodistrian University of Athens, Athens, Greece

    Christos Koromilas, Charis Liapi, Konstantinos Kalafatakis & Apostolos Zarros

  2. Institute of Child Health, “Aghia Sophia” Children’s Hospital, Athens, Greece

    Kleopatra H. Schulpis

  3. Department of Physiology, Medical School, National & Kapodistrian University of Athens, P.O. Box 65257, Athens, GR-15401, Greece

    Apostolos Zarros & Stylianos Tsakiris

Authors
  1. Christos Koromilas
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  2. Charis Liapi
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  3. Kleopatra H. Schulpis
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  4. Konstantinos Kalafatakis
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  5. Apostolos Zarros
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  6. Stylianos Tsakiris
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Corresponding author

Correspondence to Stylianos Tsakiris.

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Koromilas, C., Liapi, C., Schulpis, K.H. et al. Structural and functional alterations in the hippocampus due to hypothyroidism. Metab Brain Dis 25, 339–354 (2010). https://doi.org/10.1007/s11011-010-9208-8

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  • DOI: https://doi.org/10.1007/s11011-010-9208-8

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