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PTU‐induced hypothyroidism in rats leads to several early neuropathological signs of Alzheimer's disease in the hippocampus and spatial memory impairments
Author(s) -
Chaalal Amina,
Poirier Roseline,
Blum David,
Gillet Brigitte,
Blanc Pascale,
Basquin Marie,
Buée Luc,
Laroche Serge,
Enderlin Valérie
Publication year - 2014
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.22319
Subject(s) - hippocampus , neuroscience , hippocampal formation , psychology , synaptic plasticity , creb , medicine , chemistry , transcription factor , receptor , biochemistry , gene
The multifactorial causes impacting the risk of developing sporadic forms of Alzheimer's disease (AD) remain to date poorly understood. Epidemiologic studies in humans and research in rodents have suggested that hypothyroidism could participate in the etiology of AD. Recently, we reported that adult‐onset hypothyroidism in rats favors β‐amyloid peptide production in the hippocampus. Here, using the same hypothyroidism model with the antithyroid molecule propythiouracyl (PTU), we further explored AD‐related features, dysfunctional cell‐signaling mechanisms and hippocampal‐dependent learning and memory. In vivo MRI revealed a progressive decrease in cerebral volume of PTU‐treated rats. In the hippocampus, hypothyroidism resulted in tau hyperphosphorylation and increases in several proinflammatory cytokines. These modifications were associated with impaired spatial memory and reduced hippocampal expression of signaling molecules important for synaptic plasticity and memory, including neurogranin, CaMKII, ERK, GSK3β, CREB, and expression of the transcription factor EGR1/Zif268. These data strengthen the idea that hypothyroidism represents an important factor influencing the risk of developing sporadic forms of AD. © 2014 Wiley Periodicals, Inc.