HYPOTHYROIDISM IN THE ADULT RAT CAUSES AN INCREMENT OF BDNF IN THE BRAIN, NEURONAL AND ASTROCYTE APOPTOSIS, GLIOSIS AND DETERIORATION OF THE POSTSYNAPTIC DENSITY.

Abstract

Background: Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though 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 6Propyl-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 ELISA and in situ hybridization. The glutamatergic synapse and the postsynaptic density (PSD) were analyzed by electron microscopy. The content of postsynaptic density 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, as well as reactive gliosis as compared to 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 as compared 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. Page 3 of 36