title: PTU-induced hypothyroidism in rats leads to several early neuropathological signs of Alzheimer's disease in the hippocampus and spatial memory impairments.
abstract: 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.
authors: Centre de Neurosciences Paris-Sud, CNRS, UMR 8195, F-91405, Orsay, France; Université Paris-Sud, UMR 8195, F-91405, Orsay, France.
authors: Amina
authors: A
authors: Chaalal
authors: Roseline
authors: R
authors: Poirier
authors: David
authors: D
authors: Blum
authors: Brigitte
authors: B
authors: Gillet
authors: Pascale
authors: P
authors: Le Blanc
authors: Marie
authors: M
authors: Basquin
authors: Luc
authors: L
authors: Buée
authors: Serge
authors: S
authors: Laroche
authors: Valérie
authors: V
authors: Enderlin
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001007:Anxiety / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D007037:Hypothyroidism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology*; D009043:Motor Activity / Q000502:physiology; D015213:Neuroimmunomodulation / Q000502:physiology; D009929:Organ Size; D010766:Phosphorylation; D011897:Random Allocation; D017208:Rats, Wistar; D065852:Spatial Memory; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016207:Cytokines; C489131:Mapt protein, rat; D016875:tau Proteins
keywords: behavior; inflammation; risk factor; signaling pathways; tau