Transthyretin knockout mice display decreased susceptibility to AMPA-induced neurodegeneration.
Transthyretin (TTR) has been regarded as a neuroprotective protein given that TTR knockout (KO) mice display increased susceptibility for amyloid beta deposition and memory deficits during aging. In parallel, TTR KO mice have increased levels of neuropeptide Y (NPY), which promotes neuroprotection and neuroproliferation. In this work, we aimed at evaluating TTR neuroprotective effect against an excitotoxic insult that is known to be prevented by NPY action. We show that despite a putative neuroprotective role of TTR, hippocampal slice cultures from TTR KO mice display a decreased susceptibility to AMPA-induced neurodegeneration. We also suggest that increased NPY levels in TTR KO mice are not associated with increased cell proliferation in the dentate gyrus or subventricular zone. In summary, the alleged neuroprotective role of TTR in the nervous system should be regarded with caution and should not be generalized to all types of insults.
Nunes
Ana Filipa
AF
Nerve Regeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Portugal.
Montero
Maria
M
Franquinho
Filipa
F
Santos
Sofia Duque
SD
Malva
João
J
Zimmer
Jens
J
Sousa
Mónica Mendes
MM
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000473:pathology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000235:genetics*; D009924:Organ Culture Techniques; D011228:Prealbumin / Q000235:genetics* / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D000963:Antimetabolites; D018690:Excitatory Amino Acid Agonists; D011228:Prealbumin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001973:Bromodeoxyuridine