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.