Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density

Claudia Cortés, Eliseo Eugenin, Esteban Aliaga, Leandro J. Carreño, Susan M. Bueno, Pablo A. Gonzalez, Silvina Gayol, David Naranjo, Verónica Noches, Michelle P. Marassi, Doris Rosenthal, Cindy Jadue, Paula Ibarra, Cecilia Keitel, Nelson Wohllk, Felipe Court, Alexis M. Kalergis, Claudia A. Riedel

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T4) 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.

Original languageEnglish (US)
Pages (from-to)951-963
Number of pages13
JournalThyroid
Volume22
Issue number9
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

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Post-Synaptic Density
Gliosis
Brain-Derived Neurotrophic Factor
Hypothyroidism
Astrocytes
Apoptosis
Hippocampus
Receptor Protein-Tyrosine Kinases
Synapses
Hippocampal CA3 Region
Learning
trkB Receptor
Propylthiouracil
Nerve Growth Factors
Confocal Microscopy
In Situ Hybridization
Sprague Dawley Rats
Electron Microscopy
Enzyme-Linked Immunosorbent Assay
Neurons

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density. / Cortés, Claudia; Eugenin, Eliseo; Aliaga, Esteban; Carreño, Leandro J.; Bueno, Susan M.; Gonzalez, Pablo A.; Gayol, Silvina; Naranjo, David; Noches, Verónica; Marassi, Michelle P.; Rosenthal, Doris; Jadue, Cindy; Ibarra, Paula; Keitel, Cecilia; Wohllk, Nelson; Court, Felipe; Kalergis, Alexis M.; Riedel, Claudia A.

In: Thyroid, Vol. 22, No. 9, 01.09.2012, p. 951-963.

Research output: Contribution to journalArticle

Cortés, C, Eugenin, E, Aliaga, E, Carreño, LJ, Bueno, SM, Gonzalez, PA, Gayol, S, Naranjo, D, Noches, V, Marassi, MP, Rosenthal, D, Jadue, C, Ibarra, P, Keitel, C, Wohllk, N, Court, F, Kalergis, AM & Riedel, CA 2012, 'Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density', Thyroid, vol. 22, no. 9, pp. 951-963. https://doi.org/10.1089/thy.2010.0400
Cortés, Claudia ; Eugenin, Eliseo ; Aliaga, Esteban ; Carreño, Leandro J. ; Bueno, Susan M. ; Gonzalez, Pablo A. ; Gayol, Silvina ; Naranjo, David ; Noches, Verónica ; Marassi, Michelle P. ; Rosenthal, Doris ; Jadue, Cindy ; Ibarra, Paula ; Keitel, Cecilia ; Wohllk, Nelson ; Court, Felipe ; Kalergis, Alexis M. ; Riedel, Claudia A. / Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density. In: Thyroid. 2012 ; Vol. 22, No. 9. pp. 951-963.
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T1 - Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density

AU - Cortés, Claudia

AU - Eugenin, Eliseo

AU - Aliaga, Esteban

AU - Carreño, Leandro J.

AU - Bueno, Susan M.

AU - Gonzalez, Pablo A.

AU - Gayol, Silvina

AU - Naranjo, David

AU - Noches, Verónica

AU - Marassi, Michelle P.

AU - Rosenthal, Doris

AU - Jadue, Cindy

AU - Ibarra, Paula

AU - Keitel, Cecilia

AU - Wohllk, Nelson

AU - Court, Felipe

AU - Kalergis, Alexis M.

AU - Riedel, Claudia A.

PY - 2012/9/1

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N2 - Background: Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T4) 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.

AB - Background: Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T4) 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.

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