TY - JOUR
T1 - No evidence in support of a prodromal respiratory control signature in the TgF344-AD rat model of Alzheimer’s disease
AU - Lucking, Eric F.
AU - Murphy, Kevin H.
AU - Burns, David P.
AU - Jaisimha, Anirudh V.
AU - Barry-Murphy, Kevin J.
AU - Dhaliwal, Pardeep
AU - Boland, Barry
AU - Rae, Mark G.
AU - O’Halloran, Ken D.
AU - O'Halloran, Ken D.
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/7
Y1 - 2019/7
N2 - Alzheimer's disease (AD) is a progressive neurodegenerative condition disturbing major brain networks, including those pivotal to the motor control of breathing. The aim of this study was to examine respiratory control in the TgF344-AD transgenic rat model of AD. At 8–11 months of age, basal minute ventilation and ventilatory responsiveness to chemostimulation were equivalent in conscious wild-type (WT) and TgF344-AD rats. Under urethane anesthesia, basal diaphragm and genioglossus EMG activities were similar in WT and TgF344-AD rats. The duration of phenylbiguanide-induced apnoea was significantly shorter in TgF344-AD rats compared with WT. Following bilateral cervical vagotomy, diaphragm and genioglossus EMG responsiveness to chemostimulation were intact in TgF344-AD rats. Amyloid precursor protein C-terminal fragments were elevated in the TgF344-AD brainstem, in the absence of amyloid-β accumulation or alterations in tau phosphorylation. Brainstem pro-inflammatory cytokine concentrations were not increased in TgF344-AD rats. We conclude that neural control of breathing is preserved in TgF344-AD rats at this stage of the disease.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative condition disturbing major brain networks, including those pivotal to the motor control of breathing. The aim of this study was to examine respiratory control in the TgF344-AD transgenic rat model of AD. At 8–11 months of age, basal minute ventilation and ventilatory responsiveness to chemostimulation were equivalent in conscious wild-type (WT) and TgF344-AD rats. Under urethane anesthesia, basal diaphragm and genioglossus EMG activities were similar in WT and TgF344-AD rats. The duration of phenylbiguanide-induced apnoea was significantly shorter in TgF344-AD rats compared with WT. Following bilateral cervical vagotomy, diaphragm and genioglossus EMG responsiveness to chemostimulation were intact in TgF344-AD rats. Amyloid precursor protein C-terminal fragments were elevated in the TgF344-AD brainstem, in the absence of amyloid-β accumulation or alterations in tau phosphorylation. Brainstem pro-inflammatory cytokine concentrations were not increased in TgF344-AD rats. We conclude that neural control of breathing is preserved in TgF344-AD rats at this stage of the disease.
KW - Amyloid precursor protein
KW - Neuroinflammation
KW - Presenilin-1
KW - Pulmonary chemoreflex
KW - Respiratory behaviour
UR - https://doi.org/10.1016/j.resp.2018.06.014
UR - https://www.scopus.com/pages/publications/85049343496
U2 - 10.1016/j.resp.2018.06.014
DO - 10.1016/j.resp.2018.06.014
M3 - Article
C2 - 29969703
VL - 265
SP - 55
EP - 67
JO - Respiratory Physiology & Neurobiology
JF - Respiratory Physiology & Neurobiology
ER -