PMID- 22870949
OWN - NLM
STAT- MEDLINE
DCOM- 20130204
LR  - 20211021
IS  - 1557-9077 (Electronic)
IS  - 1050-7256 (Print)
IS  - 1050-7256 (Linking)
VI  - 22
IP  - 9
DP  - 2012 Sep
TI  - Hypothyroidism in the adult rat causes incremental changes in brain-derived 
      neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration 
      of postsynaptic density.
PG  - 951-63
LID - 10.1089/thy.2010.0400 [doi]
AB  - BACKGROUND: Adult hypothyroidism is a highly prevalent condition that impairs 
      processes, such as learning and memory. Even though tetra-iodothyronine (T(4)) 
      treatment can overcome the hypothyroidism in the majority of cases, it cannot 
      fully recover the patient's learning capacity and memory. In this work, we 
      analyzed the cellular and molecular changes in the adult brain occurring with the 
      development of experimental hypothyroidism. METHODS: Adult male Sprague-Dawley 
      rats were treated with 6-propyl-2-thiouracil (PTU) for 20 days to induce 
      hypothyroidism. Neuronal and astrocyte apoptosis were analyzed in the hippocampus 
      of control and hypothyroid adult rats by confocal microscopy. The content of 
      brain-derived neurotrophic factor (BDNF) was analyzed using enzyme-linked 
      immunosorbent assay (ELISA) and in situ hybridization. The glutamatergic synapse 
      and the postsynaptic density (PSD) were analyzed by electron microscopy. The 
      content of PSD proteins like tyrosine receptor kinase B (TrkB), p75, and 
      N-methyl-D-aspartate receptor (NMDAr) were analyzed by immunoblot. RESULTS: We 
      observed that the hippocampus of hypothyroid adult rats displayed increased 
      apoptosis levels in neurons and astrocyte and reactive gliosis compared with 
      controls. Moreover, we found that the amount of BDNF mRNA was higher in the 
      hippocampus of hypothyroid rats and the content of TrkB, the receptor for BDNF, 
      was reduced at the PSD of the CA3 region of hypothyroid rats, compared with 
      controls. We also observed that the glutamatergic synapses from the stratum 
      radiatum of CA3 from hypothyroid rats, contained thinner PSDs than control rats. 
      This observation was in agreement with a reduced content of NMDAr subunits at the 
      PSD in hypothyroid animals. CONCLUSIONS: Our data suggest that adult 
      hypothyroidism affects the hippocampus by a mechanism that alters the composition 
      of PSD, reduces neuronal and astrocyte survival, and alters the content of the 
      signaling neurotrophic factors, such as BDNF.
FAU - Cortes, Claudia
AU  - Cortes C
AD  - Millennium Institute on Immunology and Immunotherapy, Department of Biological 
      Sciences, Faculty of Biological Sciences and Faculty of Medicine, Andres Bello 
      University, Santiago, Chile.
FAU - Eugenin, Eliseo
AU  - Eugenin E
FAU - Aliaga, Esteban
AU  - Aliaga E
FAU - Carreno, Leandro J
AU  - Carreno LJ
FAU - Bueno, Susan M
AU  - Bueno SM
FAU - Gonzalez, Pablo A
AU  - Gonzalez PA
FAU - Gayol, Silvina
AU  - Gayol S
FAU - Naranjo, David
AU  - Naranjo D
FAU - Noches, Veronica
AU  - Noches V
FAU - Marassi, Michelle P
AU  - Marassi MP
FAU - Rosenthal, Doris
AU  - Rosenthal D
FAU - Jadue, Cindy
AU  - Jadue C
FAU - Ibarra, Paula
AU  - Ibarra P
FAU - Keitel, Cecilia
AU  - Keitel C
FAU - Wohllk, Nelson
AU  - Wohllk N
FAU - Court, Felipe
AU  - Court F
FAU - Kalergis, Alexis M
AU  - Kalergis AM
FAU - Riedel, Claudia A
AU  - Riedel CA
LA  - eng
GR  - R01 MH096625/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120807
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (Antithyroid Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 721M9407IY (Propylthiouracil)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Antithyroid Agents/adverse effects
MH  - Apoptosis/drug effects
MH  - Astrocytes/drug effects/*pathology
MH  - Brain-Derived Neurotrophic Factor/analysis/*metabolism
MH  - Gliosis/chemically induced/*pathology
MH  - Hippocampus/chemistry/drug effects/pathology/ultrastructure
MH  - Hypothyroidism/chemically induced/*complications
MH  - Male
MH  - Neurons/drug effects/*pathology
MH  - Post-Synaptic Density/chemistry/drug effects/*pathology
MH  - Propylthiouracil/adverse effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/analysis
MH  - Receptors, N-Methyl-D-Aspartate/analysis
PMC - PMC3429274
EDAT- 2012/08/09 06:00
MHDA- 2013/02/05 06:00
PMCR- 2013/09/01
CRDT- 2012/08/09 06:00
PHST- 2012/08/09 06:00 [entrez]
PHST- 2012/08/09 06:00 [pubmed]
PHST- 2013/02/05 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - 10.1089/thy.2010.0400 [pii]
AID - 10.1089/thy.2010.0400 [doi]
PST - ppublish
SO  - Thyroid. 2012 Sep;22(9):951-63. doi: 10.1089/thy.2010.0400. Epub 2012 Aug 7.