Upper airway dysfunction of Tau-P301L mice correlates with tauopathy in midbrain and ponto-medullary brainstem nuclei
- PMID: 20130190
- PMCID: PMC6633985
- DOI: 10.1523/JNEUROSCI.5261-09.2010
Upper airway dysfunction of Tau-P301L mice correlates with tauopathy in midbrain and ponto-medullary brainstem nuclei
Abstract
Tauopathy comprises hyperphosphorylation of the microtubule-associated protein tau, causing intracellular aggregation and accumulation as neurofibrillary tangles and neuropil treads. Some primary tauopathies are linked to mutations in the MAPT gene coding for protein tau, but most are sporadic with unknown causes. Also, in Alzheimer's disease, the most frequent secondary tauopathy, neither the cause nor the pathological mechanisms and repercussions are understood. Transgenic mice expressing mutant Tau-P301L suffer cognitive and motor defects and die prematurely from unknown causes. Here, in situ electrophysiology in symptomatic Tau-P301L mice (7-8 months of age) revealed reduced postinspiratory discharges of laryngeal motor outputs that control laryngeal constrictor muscles. Under high chemical drive (hypercapnia), postinspiratory discharge was nearly abolished, whereas laryngeal inspiratory discharge was increased disproportionally. The latter may suggest a shift of postinspiratory laryngeal constrictor activity into inspiration. In vivo double-chamber plethysmography of Tau-P301L mice showed significantly reduced respiratory airflow but significantly increased chest movements during baseline breathing, but particularly in hypercapnia, confirming a significant increase in inspiratory resistive load. Histological analysis demonstrated hyperphosphorylated tau in brainstem nuclei, directly or indirectly involved in upper airway motor control (i.e., the Kölliker-Fuse, periaqueductal gray, and intermediate reticular nuclei). In contrast, young Tau-P301L mice did not show breathing disorders or brainstem tauopathy. Consequently, in aging Tau-P301L mice, progressive upper airway dysfunction is linked to progressive tauopathy in identified neural circuits. Because patients with tauopathy suffer from upper airway dysfunction, the Tau-P301L mice can serve as an experimental model to study disease-specific synaptic dysfunction in well defined functional neural circuits.
Figures







Similar articles
-
Age-related impairment of ultrasonic vocalization in Tau.P301L mice: possible implication for progressive language disorders.PLoS One. 2011;6(10):e25770. doi: 10.1371/journal.pone.0025770. Epub 2011 Oct 12. PLoS One. 2011. PMID: 22022446 Free PMC article.
-
Raphé tauopathy alters serotonin metabolism and breathing activity in terminal Tau.P301L mice: possible implications for tauopathies and Alzheimer's disease.Respir Physiol Neurobiol. 2011 Sep 15;178(2):290-303. doi: 10.1016/j.resp.2011.06.030. Epub 2011 Jul 6. Respir Physiol Neurobiol. 2011. PMID: 21763469
-
Phosphorylation of protein Tau by GSK3β prolongs survival of bigenic Tau.P301L×GSK3β mice by delaying brainstem tauopathy.Neurobiol Dis. 2014 Jul;67:119-32. doi: 10.1016/j.nbd.2014.03.016. Epub 2014 Apr 2. Neurobiol Dis. 2014. PMID: 24704314
-
Tau Interacting Proteins: Gaining Insight into the Roles of Tau in Health and Disease.Adv Exp Med Biol. 2019;1184:145-166. doi: 10.1007/978-981-32-9358-8_13. Adv Exp Med Biol. 2019. PMID: 32096036 Review.
-
Tauopathy: A common mechanism for neurodegeneration and brain aging.Mech Ageing Dev. 2019 Mar;178:72-79. doi: 10.1016/j.mad.2019.01.007. Epub 2019 Jan 19. Mech Ageing Dev. 2019. PMID: 30668956 Free PMC article. Review.
Cited by
-
Contributions of the Kölliker-Fuse nucleus to coordination of breathing and swallowing.Respir Physiol Neurobiol. 2013 Oct 1;189(1):10-21. doi: 10.1016/j.resp.2013.06.003. Epub 2013 Jun 14. Respir Physiol Neurobiol. 2013. PMID: 23774145 Free PMC article.
-
O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies.ACS Chem Neurosci. 2022 Apr 20;13(8):1296-1314. doi: 10.1021/acschemneuro.2c00057. Epub 2022 Mar 31. ACS Chem Neurosci. 2022. PMID: 35357812 Free PMC article.
-
Protein tau: prime cause of synaptic and neuronal degeneration in Alzheimer's disease.Int J Alzheimers Dis. 2012;2012:251426. doi: 10.1155/2012/251426. Epub 2012 Jun 8. Int J Alzheimers Dis. 2012. PMID: 22720188 Free PMC article.
-
Anesthesia and tau pathology.Prog Neuropsychopharmacol Biol Psychiatry. 2013 Dec 2;47:147-55. doi: 10.1016/j.pnpbp.2013.03.004. Epub 2013 Mar 25. Prog Neuropsychopharmacol Biol Psychiatry. 2013. PMID: 23535147 Free PMC article. Review.
-
Age-related impairment of ultrasonic vocalization in Tau.P301L mice: possible implication for progressive language disorders.PLoS One. 2011;6(10):e25770. doi: 10.1371/journal.pone.0025770. Epub 2011 Oct 12. PLoS One. 2011. PMID: 22022446 Free PMC article.
References
-
- Alheid GF, Milsom WK, McCrimmon DR. Pontine influences on breathing: an overview. Respir Physiol Neurobiol. 2004;143:105–114. - PubMed
-
- Andorfer CA, Davies P. PKA phosphorylations on tau: developmental studies in the mouse. Dev Neurosci. 2000;22:303–309. - PubMed
-
- Ballantyne D, Andrzejewski M, Mückenhoff K, Scheid P. Rhythms, synchrony and electrical coupling in the locus coeruleus. Respir Physiol Neurobiol. 2004;143:199–214. - PubMed
-
- Besnard S, Denise P, Cappelin B, Dutschmann M, Gestreau C. Stimulation of the rat medullary raphe nuclei induces differential responses in respiratory muscle activity. Respir Physiol Neurobiol. 2009;165:208–214. - PubMed
-
- Boekhoorn K, Terwel D, Biemans B, Borghgraef P, Wiegert O, Ramakers GJ, de Vos K, Krugers H, Tomiyama T, Mori H, Joels M, van Leuven F, Lucassen PJ. Improved long-term potentiation and memory in young tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathy. J Neurosci. 2006;26:3514–3523. - PMC - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases