Tauopathy in the Ponto‐Medullary Brainstem Nuclei of Aged Tau‐P301L Mice

Abstract

We recently identified key brainstem areas critically involved in coordinating swallowing and breathing: 1) Nucleus of the solitary tract (NTS), which generates a phasic or rhythmic ‘command’ to produce sequential swallowing in response to sensory stimuli; and 2) Kölliker‐Fuse nucleus (KF), which provides tonic drive for the laryngeal adductors and completely seals the trachea during, and between, swallows. Our aim was to identify whether an underlying pathology exists in the NTS and KF of an established model of neurodegeneration, the Tau‐P301 mouse, and humans that suffered from dementia, which may link dementia and swallowing dysfunction.Tauopathy and neurofibrillary tangle‐related neuropathological morphology was identified by immunohistochemistry using antisera raised against phosphorylated tau. Double‐fluorescence immunohistochemistry was performed to characterise the identity and functionality of cell bodies expressing phosphorylated tau.Cell bodies immunopositive for phosphorylated tau were distributed within the KF, and to a lesser degree, NTS, of Tau‐P301 mice, and the KF of dementia patients with a history of swallowing disorder. This coincided with an upregulated density/intensity of GABA and GAD67 immunoreactivity in fibers/terminals within the KF. Tau positive cell bodies in the KF coexpressed the transcription factor FOXP2.Respiratory‐related neurons in the brainstem are susceptible to neurodegeneration in Tau‐P301 mice and humans suffering dementia, which may disrupt the KF's control of laryngeal adductor motor neurons in the NA and lead to miscoordinated swallowing/breathing patterns.