title: MRNA Levels of ACh-Related Enzymes in the Hippocampus of THY-Tau22 Mouse: A Model of Human Tauopathy with No Signs of Motor Disturbance.
abstract: The microtubule-associated protein Tau tends to form aggregates in neurodegenerative disorders referred to as tauopathies. The tauopathy model transgenic (Tg) THY-Tau22 (Tau22) mouse shows disturbed septo-hippocampal transmission, memory deficits and no signs of motor dysfunction. The reports showing a hippocampal downregulation of choline acetyltransferase (ChAT) in SAMP8 mice, a model of aging, and an upregulation of acetylcholinesterase (AChE) in Tg-VLW mice, a model of FTDP17 tauopathy, may lead to think that the supply of ACh to the hippocampus can be threatened as aging or Tau pathology progress. The above was tested by comparing the mRNA levels for ACh-related enzymes in hippocampi of wild-type (wt) and Tau22 mice at ages when the neuropathological signs are debuting (3-4 months), moderate (6-7 months) and extensive (>9 months). Age-matched Tau22 and wt mice hippocampi displayed similar ChAT, AChE-T, butyrylcholinesterase (BChE) and a proline-rich membrane anchor (PRiMA) mRNA levels, any change most likely arising from ACh homeostasis. The unchanged hippocampal levels of AChE-T mRNA and enzyme activity observed in Tau22 mice, expressing G272V-P301S hTau, differed from the increase in AChE-T mRNA and activity observed in Tg-VLW mice, expressing G272V-P301L-R406W hTau. The difference supports the idea that AChE upregulation may proceed or not depending on the particular Tau mutation, which would dictate Tau folding, the accessibility/affinity to kinases and phosphatases, and P-Tau aggregation with itself and protein partners, transcription factors included.
authors.affiliation: Departamento de Bioquímica y Biología Molecular-A, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Beatriz E
authors.initials: BE
authors.lastname: García-Gómez
authors.affiliation: INSERM U837 Alzheimer and Tauopathies, Institute of Predictive Medicine and Therapeutic Research, Université Lille Nord de France, Lille, France.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Fernández-Gómez
authors.affiliation: Departamento de Bioquímica y Biología Molecular-A, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Encarnación
authors.initials: E
authors.lastname: Muñoz-Delgado
authors.affiliation: INSERM U837 Alzheimer and Tauopathies, Institute of Predictive Medicine and Therapeutic Research, Université Lille Nord de France, Lille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.affiliation: INSERM U837 Alzheimer and Tauopathies, Institute of Predictive Medicine and Therapeutic Research, Université Lille Nord de France, Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.affiliation: Departamento de Bioquímica y Biología Molecular-A, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain. cevidal@um.es.|Departamento de Bioquímica y Biología Molecular-A, Edificio de Veterinaria, Universidad de Murcia, Apdo. 4021, E-30071, Espinardo, Murcia, Spain. cevidal@um.es.
authors.forename: Cecilio J
authors.initials: CJ
authors.lastname: Vidal
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000235:genetics / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009068:Movement; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity; D024801:Tauopathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016875:tau Proteins / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C486718:prima1 protein, mouse; D016875:tau Proteins; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000109:Acetylcholine
keywords: Acetylcholinesterase; Alzheimer’s disease; Butyrylcholinesterase; Choline acetyltransferase; Proline-rich membrane anchor