PMID- 23201250
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20130415
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 239
DP  - 2013 Jun 3
TI  - Developmental thyroid hormone insufficiency and brain development: a role for 
      brain-derived neurotrophic factor (BDNF)?
PG  - 253-70
LID - S0306-4522(12)01133-5 [pii]
LID - 10.1016/j.neuroscience.2012.11.022 [doi]
AB  - Thyroid hormones (TH) are essential for normal brain development. Even modest 
      degrees of TH disruption experienced in utero can result in neuropsychological 
      deficits in children despite normal thyroid status at birth. Neurotrophins have 
      been implicated in a host of brain cellular functions, and in particular, 
      brain-derived neurotrophic factor (BDNF) has a well documented role in 
      development and function of the nervous system. A number of laboratories have 
      reported the effects of TH administration or severe deprivation on neurotrophin 
      expression in brain. This review provides an overview and update of recent 
      developments in the thyroid field as they relate to the nervous system. Secondly, 
      we describe an animal model of low level TH insufficiency that is more relevant 
      for studying the neurological consequences associated with the modest TH 
      perturbations of subclinical hypothyroidism, or that would be anticipated from 
      exposure to environmental contaminants with a mode-of-action that involves the 
      thyroid. Finally, we review the available in vivo literature on TH-mediated 
      alterations in neurotrophins, particularly BDNF, and discuss their possible 
      contribution to brain impairments associated with TH insufficiency. The 
      observations of altered BDNF protein and gene expression have varied as a 
      function of hypothyroid model, age, and brain region assessed. Only a handful of 
      studies have investigated the relationship of neurotrophins and TH using models 
      of TH deprivation that are not severe, and dose-response information is sparse. 
      Differences in the models used, species, doses, regions assessed, age at 
      assessment, and method employed make it difficult to reach a consensus. Based on 
      the available literature, the case for a direct role for BDNF in thyroid-mediated 
      effects in the brain is not compelling. We conclude that delineation of the 
      potential role of neurotrophins in TH-mediated neuronal development may be more 
      fruitful by examining additional neurotrophins (e.g., nerve growth factor), 
      moderate degrees of TH insufficiency, and younger ages. We further suggest that 
      investigation of BDNF invoked by synaptic activation (i.e., plasticity, 
      enrichment, trauma) may serve to elucidate a role of thyroid hormone in 
      BDNF-regulated synaptic function.
CI  - Published by Elsevier Ltd.
FAU - Gilbert, M E
AU  - Gilbert ME
AD  - Toxicity Assessment Division, Neurotoxicology Branch, U.S. Environmental 
      Protection Agency, Research Triangle Park, NC, USA. gilbert.mary@epa.gov
FAU - Lasley, S M
AU  - Lasley SM
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20121129
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Thyroid Hormones)
SB  - IM
MH  - Animals
MH  - Brain/*growth & development/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Humans
MH  - Thyroid Hormones/*deficiency
EDAT- 2012/12/04 06:00
MHDA- 2013/10/18 06:00
CRDT- 2012/12/04 06:00
PHST- 2012/11/02 00:00 [received]
PHST- 2012/11/06 00:00 [accepted]
PHST- 2012/12/04 06:00 [entrez]
PHST- 2012/12/04 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
AID - S0306-4522(12)01133-5 [pii]
AID - 10.1016/j.neuroscience.2012.11.022 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Jun 3;239:253-70. doi: 10.1016/j.neuroscience.2012.11.022. 
      Epub 2012 Nov 29.