title: Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density.
abstract: 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.
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Department of Biological Sciences, Faculty of Biological Sciences and Faculty of Medicine, Andrés Bello University, Santiago, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cortés
authors.forename: Eliseo
authors.initials: E
authors.lastname: Eugenin
authors.forename: Esteban
authors.initials: E
authors.lastname: Aliaga
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Carreño
authors.forename: Susan M
authors.initials: SM
authors.lastname: Bueno
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Gonzalez
authors.forename: Silvina
authors.initials: S
authors.lastname: Gayol
authors.forename: David
authors.initials: D
authors.lastname: Naranjo
authors.forename: Verónica
authors.initials: V
authors.lastname: Noches
authors.forename: Michelle P
authors.initials: MP
authors.lastname: Marassi
authors.forename: Doris
authors.initials: D
authors.lastname: Rosenthal
authors.forename: Cindy
authors.initials: C
authors.lastname: Jadue
authors.forename: Paula
authors.initials: P
authors.lastname: Ibarra
authors.forename: Cecilia
authors.initials: C
authors.lastname: Keitel
authors.forename: Nelson
authors.initials: N
authors.lastname: Wohllk
authors.forename: Felipe
authors.initials: F
authors.lastname: Court
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Riedel
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000378:metabolism*; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D007037:Hypothyroidism / Q000139:chemically induced / Q000150:complications*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D057907:Post-Synaptic Density / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D011441:Propylthiouracil / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000032:analysis; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis
chemical_list: D013956:Antithyroid Agents; D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D011441:Propylthiouracil; D020813:Receptor, trkB