Abstract:
:Diabetes and obesity have been implicated as risk factors for dementia. However, metabolic mechanisms and associated signalling pathways have not been investigated in detail in frontotemporal dementia. We therefore here characterised physiological, behavioural and molecular phenotypes of 3- and 8-month-old male tau knock-in (PLB2TAU) vs wild-type (PLBWT) mice. Homecage analysis suggested intact habituation but a dramatic reduction in exploratory activity in PLB2TAU mice. Deficits in motor strength were also observed. At 3 months, PLB2TAU mice displayed normal glucose handling but developed hyperglycaemia at 8 months, suggesting a progressive diabetic phenotype. Brain, liver and muscle tissue analyses confirmed tissue-specific deregulation of metabolic and homeostatic pathways. In brain, increased levels of phosphorylated tau and inflammation were detected alongside reduced ER regulatory markers, overall suggesting a downregulation in essential cellular defence pathways. We suggest that subtle neuronal expression of mutated human tau is sufficient to disturb systems metabolism and protein handling. Whether respective dysfunctions in tauopathy patients are also a consequence of tau pathology remains to be confirmed, but could offer new avenues for therapeutic interventions.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Hull C,Dekeryte R,Koss DJ,Crouch B,Buchanan H,Delibegovic M,Platt Bdoi
10.1007/s12035-019-01722-6subject
Has Abstractpub_date
2020-01-01 00:00:00pages
539-550issue
1eissn
0893-7648issn
1559-1182pii
10.1007/s12035-019-01722-6journal_volume
57pub_type
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