Abstract:
:Olfactory dysfunction is a recognized risk factor for the pathogenesis of Alzheimer's disease (AD), while the mechanisms are still not clear. Here, we applied bilateral olfactory bulbectomy (OBX), an olfactory deprivation surgery to cause permanent anosmia, in human tau-overexpressed mice (htau mice) to investigate changes of AD-like pathologies including aggregation of abnormally phosphorylated tau and cholinergic neuron loss. We found that tau phosphorylation in hippocampus was increased at Thr-205, Ser-214, Thr-231, and Ser-396 after OBX. OBX also increased the level of sarkosyl-insoluble Tau at those epitopes and accelerated accumulation of somatodendritic tau. Moreover, OBX resulted in the elevation of calpain activity accompanied by an increased expression of the cyclin-dependent kinase 5 (cdk5) neuronal activators, p35 and p25, in hippocampus. Furthermore, OBX induces the loss of the cholinergic neurons in medial septal. Administration of cdk5 pharmacological inhibitor roscovitine into lateral ventricles suppressed tau hyperphosphorylation and mislocalization and restored the cholinergic neuron loss. These findings suggest that olfactory deprivation by OBX hastens tau pathology and cholinergic system impairment in htau mice possibly via activation of cdk5.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Li K,Liu FF,He CX,Huang HZ,Xie AJ,Hu F,Liu D,Wang JZ,Zhu LQdoi
10.1007/s12035-014-9007-zsubject
Has Abstractpub_date
2016-01-01 00:00:00pages
391-401issue
1eissn
0893-7648issn
1559-1182pii
10.1007/s12035-014-9007-zjournal_volume
53pub_type
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