{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:49:51Z","timestamp":1785836991242,"version":"3.56.0"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Brain degenerations in sporadic Alzheimer\u2019s disease (AD) are observed earliest in the locus coeruleus (LC), a population of noradrenergic neurons, in which hyperphosphorylated tau protein expression and \u03b2-amyloid (A\u03b2) accumulation begin. Along with this, similar changes occur in the basal forebrain cholinergic neurons, such as the nucleus basalis of Meynert. Neuronal degeneration of the two neuronal nuclei leads to a decrease in neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex, which results in the accumulation of A\u03b2 and hyperphosphorylated tau protein and ultimately causes neuronal cell death in those cortices. On the other hand, a large number of epidemiological studies have shown that tooth loss or masticatory dysfunction is a risk factor for dementia including AD, and numerous studies using experimental animals have also shown that masticatory dysfunction causes brain degeneration in the basal forebrain, hippocampus, and cerebral cortex similar to those observed in human AD, and that learning and memory functions are impaired accordingly. However, it remains unclear how masticatory dysfunction can induce such brain degeneration similar to AD, and the neural mechanism linking the trigeminal nervous system responsible for mastication and the cognitive and memory brain system remains unknown. In this review paper, we provide clues to the search for such \u201cmissing link\u201d by discussing the embryological, anatomical, and physiological relationship between LC and its laterally adjoining mesencephalic trigeminal nucleus which plays a central role in the masticatory functions.<\/jats:p>","DOI":"10.3389\/fncel.2024.1425645","type":"journal-article","created":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T20:57:07Z","timestamp":1719694627000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Search for unknown neural link between the masticatory and cognitive brain systems to clarify the involvement of its impairment in the pathogenesis of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Youngnam","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Toyoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1007\/BF00210833","article-title":"Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic-acid lesions of the nucleus basalis of Meynert","volume":"92","author":"Aigner","year":"1987","journal-title":"Psychopharmacology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/sj.mp.4000897","article-title":"Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal","volume":"6","author":"Akbarian","year":"2001","journal-title":"Mol. Psychiatry"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/367368a0","article-title":"Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo","volume":"367","author":"Arenas","year":"1994","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1146\/annurev.neuro.28.061604.135709","article-title":"An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance","volume":"28","author":"Aston-Jones","year":"2005","journal-title":"Annu. Rev. Neurosci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/s0079-6123(08)63799-1","article-title":"Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology","volume":"88","author":"Aston-Jones","year":"1991","journal-title":"Prog. Brain Res."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/j.neuron.2016.09.006","article-title":"Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline","volume":"91","author":"Ballinger","year":"2016","journal-title":"Neuron"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1007\/s004010050595","article-title":"Cholinergic fibre loss associated with diffuse plaques in the non-demented elderly: the preclinical stage of Alzheimer\u2019s disease?","volume":"93","author":"Beach","year":"1997","journal-title":"Acta Neuropathol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/s0006-8993(97)01003-2","article-title":"Mechanism and prevention of neurotoxicity caused by \u03b2-amyloid peptides: relation to Alzheimer\u2019s disease","volume":"776","author":"Blanchard","year":"1997","journal-title":"Brain Res."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1212\/wnl.32.2.164","article-title":"Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia","volume":"32","author":"Bondareff","year":"1982","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"4979","DOI":"10.2174\/1381612823666170710163411","article-title":"Astrocyte: an innovative approach for Alzheimer\u2019s disease therapy","volume":"23","author":"Bronzuoli","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1365-2842.1981.tb00469.x","article-title":"Occlusal dysfunction and stress. An experimental study in macaque monkeys","volume":"8","author":"Budtz-Jorgensen","year":"1981","journal-title":"J. Oral Rehabil."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/s0006-8993(98)01211-6","article-title":"Accumulation of 3,4-dihydroxyphenylglycolaldehyde, the neurotoxic monoamine oxidase a metabolite of norepinephrine, in locus ceruleus cell bodies in Alzheimer\u2019s disease: mechanism of neuron death","volume":"816","author":"Burke","year":"1999","journal-title":"Brain Res."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/1471-2202-8-73","article-title":"Calcium-sensitive regulation of monoamine oxidase-a contributes to the production of peroxyradicals in hippocampal cultures: implications for Alzheimer disease-related pathology","volume":"8","author":"Cao","year":"2007","journal-title":"BMC Neurosci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1146\/annurev.pharmtox.46.120604.141146","article-title":"Vesicular neurotransmitter transporters as targets for endogenous and exogenous toxic substances","volume":"48","author":"Chaudhry","year":"2008","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.freeradbiomed.2017.10.341","article-title":"Dysregulation of neurotrophin signaling in the pathogenesis of Alzheimer disease and of Alzheimer disease in Down syndrome","volume":"114","author":"Chen","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/0006-8993(94)91857-0","article-title":"NT-3 and BDNF protect CNS neurons against metabolic\/excitotoxic insults","volume":"640","author":"Cheng","year":"1994","journal-title":"Brain Res."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1146\/annurev-physchem-032511-143704","article-title":"Neurotrophin signaling via long-distance axonal transport","volume":"63","author":"Chowdary","year":"2012","journal-title":"Annu. Rev. Phys. Chem."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1111\/ejn.12858","article-title":"Generation of resonance-dependent oscillation by mGluR-I activation switches single spiking to bursting in mesencephalic trigeminal sensory neurons","volume":"41","author":"Chung","year":"2015","journal-title":"Eur. J. Neurosci."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/360672a0","article-title":"Mutation of the \u03b2-amyloid precursor protein in familial Alzheimer\u2019s disease increases \u03b2-protein production","volume":"360","author":"Citron","year":"1992","journal-title":"Nature"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/0006-8993(90)91430-o","article-title":"Dopaminergic afferents to the mesencephalic trigeminal nucleus of the rat: a light and electron microscope immunocytochemistry study","volume":"514","author":"Copray","year":"1990","journal-title":"Brain Res."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.neurobiolaging.2016.08.012","article-title":"Selective noradrenaline depletion impairs working memory and hippocampal neurogenesis","volume":"48","author":"Coradazzi","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1111\/j.1471-4159.2010.06622.x","article-title":"Noradrenaline activation of neurotrophic pathways protects against neuronal amyloid toxicity","volume":"113","author":"Counts","year":"2010","journal-title":"J. Neurochem."},{"key":"ref23","first-page":"163","article-title":"Activation of the locus coeruleus noradrenergic system by intracoerulear microinfusion of corticotropin-releasing factor: effects on discharge rate, cortical norepinephrine levels and cortical electroencephalographic activity","volume":"281","author":"Curtis","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"130","DOI":"10.3389\/fnana.2017.00130","article-title":"Trigeminal, visceral and vestibular inputs may improve cognitive functions by acting through the locus coeruleus and the ascending reticular activating system: a new hypothesis","volume":"11","author":"De Cicco","year":"2017","journal-title":"Front. Neuroanat."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e74966","DOI":"10.1371\/journal.pone.0074966","article-title":"Effects of apoE deficiency and occlusal disharmony on amyloid-beta production and spatial memory in rats","volume":"8","author":"Ekuni","year":"2013","journal-title":"PLoS One"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s12017-011-8151-0","article-title":"Occlusal disharmony increases amyloid-beta in the rat hippocampus","volume":"13","author":"Ekuni","year":"2011","journal-title":"NeuroMolecular Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/0092-8674(94)90213-5","article-title":"Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents","volume":"77","author":"Ernfors","year":"1994","journal-title":"Cell"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.mcn.2012.04.002","article-title":"Onecut factors control development of the locus coeruleus and of the mesencephalic trigeminal nucleus","volume":"50","author":"Espana","year":"2012","journal-title":"Mol. Cell. Neurosci."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1030609","DOI":"10.3389\/fphar.2022.1030609","article-title":"Selective vulnerability of the locus coeruleus noradrenergic system and its role in modulation of neuroinflammation, cognition, and neurodegeneration","volume":"13","author":"Evans","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/s0304-3940(01)02495-8","article-title":"Repeated experience of social defeats increases serotonin transporter and monoamine oxidase a mRNA levels in raphe nuclei of male mice","volume":"321","author":"Filipenko","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"12670","DOI":"10.1073\/pnas.94.23.12670","article-title":"Identification of genes differentially expressed by nerve growth factor- and neurotrophin-3-dependent sensory neurons","volume":"94","author":"Friedel","year":"1997","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref32","first-page":"259","article-title":"Amyloid beta protein deposition in normal aging has the same characteristics as that in Alzheimer\u2019s disease. Predominance of A beta 42(43) and association of A beta 40 with cored plaques","volume":"148","author":"Fukumoto","year":"1996","journal-title":"Am. J. Pathol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1177\/0022034517708771","article-title":"Reduced mastication impairs memory function","volume":"96","author":"Fukushima-Nakayama","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1002\/cne.22559","article-title":"Reassessment of the structural basis of the ascending arousal system","volume":"519","author":"Fuller","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"6409","DOI":"10.1038\/s41598-022-10321-w","article-title":"Molar loss induces hypothalamic and hippocampal astrogliosis in aged mice","volume":"12","author":"Furukawa","year":"2022","journal-title":"Sci. Rep."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.jalz.2006.01.002","article-title":"Potentially modifiable risk factors for dementia in identical twins","volume":"2","author":"Gatz","year":"2006","journal-title":"Alzheimers Dement."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/0047-6374(95)01657-0","article-title":"Localisation and association of pathomorphological changes at the brainstem in Alzheimer\u2019s disease","volume":"84","author":"Giess","year":"1995","journal-title":"Mech. Ageing Dev."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1212\/01.WNL.0000159740.16984.3C","article-title":"Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial","volume":"64","author":"Gilman","year":"2005","journal-title":"Neurology"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1126\/science.3810169","article-title":"Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer\u2019s disease","volume":"235","author":"Goldgaber","year":"1987","journal-title":"Science"},{"key":"ref40","first-page":"21","article-title":"Evidence of neuronal oxidative damage in Alzheimer\u2019s disease","volume":"149","author":"Good","year":"1996","journal-title":"Am. J. Pathol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.3233\/JAD-200257","article-title":"Neurodegeneration of trigeminal mesencephalic neurons by the tooth loss triggers the progression of Alzheimer\u2019s disease in 3xTg-AD model mice","volume":"76","author":"Goto","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.neubiorev.2017.09.017","article-title":"The role of central and medial amygdala in normal and abnormal aggression: a review of classical approaches","volume":"85","author":"Haller","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.cell.2016.12.027","article-title":"Integrated control of predatory hunting by the central nucleus of the amygdala","volume":"168","author":"Han","year":"2017","journal-title":"Cell"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"6058","DOI":"10.1073\/pnas.0909586107","article-title":"Locus ceruleus controls Alzheimer\u2019s disease pathology by modulating microglial functions through norepinephrine","volume":"107","author":"Heneka","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jdsr.2009.12.002","article-title":"Occlusal-masticatory function and learning and memory: Immunohistochemical, biochemical, behavioral and electrophysiological studies in rats","volume":"46","author":"Hirai","year":"2010","journal-title":"Jap. Dent. Sci. Rev."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.neures.2008.11.004","article-title":"Basal forebrain stimulation induces NGF secretion in ipsilateral parietal cortex via nicotinic receptor activation in adult, but not aged rats","volume":"63","author":"Hotta","year":"2009","journal-title":"Neurosci. Res."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e0190741","DOI":"10.1371\/journal.pone.0190741","article-title":"Occlusal force is correlated with cognitive function directly as well as indirectly via food intake in community-dwelling older Japanese: from the SONIC study","volume":"13","author":"Ikebe","year":"2018","journal-title":"PLoS One"},{"key":"ref48","first-page":"63","article-title":"A case-control study of risk factors associated with Alzheimer type dementia in Japan","volume-title":"Studies in Alzheimer\u2019s disease: epidemiology and risk factors proceedings of the third international symposium on dementia","author":"Isse","year":"1991"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","article-title":"Hypothetical model of dynamic biomarkers of the Alzheimer\u2019s pathological cascade","volume":"9","author":"Jack","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1212\/wnl.45.9.1691","article-title":"Neuropsychological characteristics of preclinical dementia in Parkinson\u2019s disease","volume":"45","author":"Jacobs","year":"1995","journal-title":"Neurology"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1172\/JCI130513","article-title":"Norepinephrine metabolite DOPEGAL activates AEP and pathological tau aggregation in locus coeruleus","volume":"130","author":"Kang","year":"2020","journal-title":"J. Clin. Invest."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/s41594-022-00745-3","article-title":"Tau modification by the norepinephrine metabolite DOPEGAL stimulates its pathology and propagation","volume":"29","author":"Kang","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1152\/jn.01191.2006","article-title":"Involvement of persistent Na+ current in spike initiation in primary sensory neurons of the rat mesencephalic trigeminal nucleus","volume":"97","author":"Kang","year":"2007","journal-title":"J. Neurophysiol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/s0166-4328(97)86078-0","article-title":"The effect of the loss of molar teeth on spatial memory and acetylcholine release from the parietal cortex in aged rats","volume":"83","author":"Kato","year":"1997","journal-title":"Behav. Brain Res."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3389\/fncel.2018.00113","article-title":"Inhibition of GluR current in microvilli of sensory neurons via Na+-microdomain coupling among GluR, HCN channel, and Na+\/K+ pump","volume":"12","author":"Kawasaki","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1177\/00220345211000263","article-title":"A\u03b2 accumulation in Vmo contributes to masticatory dysfunction in 5XFAD mice","volume":"100","author":"Kim","year":"2021","journal-title":"J. Dent. Res."},{"key":"ref57","first-page":"575","article-title":"Risk factors for Alzheimer\u2019s demantia: meta-analyses by WHO-NIA-EC research group (in Japanese)","volume":"19","author":"Kondo","year":"1990","journal-title":"Jpn. J. Clin. Psychiatry"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1016\/s0006-3223(99)00164-x","article-title":"Corticotropin-releasing factor, norepinephrine, and stress","volume":"46","author":"Koob","year":"1999","journal-title":"Biol. Psychiatry"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.bbr.2012.11.012","article-title":"Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe\/PS1dE9 mice","volume":"240","author":"Laursen","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.brainres.2007.12.013","article-title":"Allowing animals to bite reverses the effects of immobilization stress on hippocampal neurotrophin expression","volume":"1195","author":"Lee","year":"2008","journal-title":"Brain Res."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/s0301-0082(03)00019-4","article-title":"Neurotrophin secretion: current facts and future prospects","volume":"69","author":"Lessmann","year":"2003","journal-title":"Prog. Neurobiol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"251","DOI":"10.3233\/JAD-141062","article-title":"Norepinephrine protects against amyloid-\u03b2 toxicity via TrkB","volume":"44","author":"Liu","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref63","first-page":"269","article-title":"Influence of diet and occlusal support on learning memory in rats behavioral and biochemical studies","volume":"107","author":"Makiura","year":"2000","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1111\/j.1600-0722.2009.00686.x","article-title":"Forebrain projections to brainstem nuclei involved in the control of mandibular movements in rats","volume":"117","author":"Mascaro","year":"2009","journal-title":"Eur. J. Oral Sci."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.tics.2016.01.001","article-title":"The locus coeruleus: essential for maintaining cognitive function and the aging brain","volume":"20","author":"Mather","year":"2016","journal-title":"Trends Cogn. Sci."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.3233\/JAD-230581","article-title":"Association of tooth loss with Alzheimer\u2019s disease tau pathologies assessed by positron emission tomography","volume":"96","author":"Matsumoto","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1089\/ars.2006.8.1997","article-title":"Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders","volume":"8","author":"Mattson","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.neuron.2015.07.002","article-title":"CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety","volume":"87","author":"Mccall","year":"2015","journal-title":"Neuron"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1478-811X-11-34","article-title":"Complexity of dopamine metabolism","volume":"11","author":"Meiser","year":"2013","journal-title":"Cell Commun. Signal"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/0306-4522(92)90292-a","article-title":"Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system","volume":"51","author":"Merlio","year":"1992","journal-title":"Neuroscience"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"6719","DOI":"10.1074\/jbc.RA118.006604","article-title":"Pyroglutamation of amyloid-\u03b2x-42 (A\u03b2x-42) followed by A\u03b21-40 deposition underlies plaque polymorphism in progressing Alzheimer's disease pathology","volume":"294","author":"Michno","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1152\/jn.1993.69.2.595","article-title":"Trigeminal premotor neurons in the bulbar parvocellular reticular formation participating in induction of rhythmical activity of trigeminal motoneurons by repetitive stimulation of the cerebral cortex in the guinea pig","volume":"69","author":"Nozaki","year":"1993","journal-title":"J. Neurophysiol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1093\/brain\/awv379","article-title":"Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer\u2019s-like pathology","volume":"139","author":"Olmos-Alonso","year":"2016","journal-title":"Brain"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"21512","DOI":"10.1074\/jbc.M600250200","article-title":"Glucocorticoid and androgen activation of monoamine oxidase A is regulated differently by R1 and Sp1","volume":"281","author":"Ou","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1002\/1531-8249(200101)49:1<53::aid-ana30>3.0.co;2-q","article-title":"The selective vulnerability of brainstem nuclei to Alzheimer\u2019s disease","volume":"49","author":"Parvizi","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref76","volume-title":"The rat brain in stereotaxic coordinates","author":"Paxinos","year":"1996"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e0237872","DOI":"10.1371\/journal.pone.0237872","article-title":"Altered mastication adversely impacts morpho-functional features of the hippocampus: a systematic review on animal studies in three different experimental conditions involving the masticatory function","volume":"15","author":"Piancino","year":"2020","journal-title":"PLoS One"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"104516","DOI":"10.1016\/j.archoralbio.2019.104516","article-title":"Adverse effects of the bite-raised condition in animal studies: a systematic review","volume":"107","author":"Piancino","year":"2019","journal-title":"Arch. Oral Biol."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1097\/NEN.0b013e318288a8dd","article-title":"Rapid \u03b2-amyloid deposition and cognitive impairment after cholinergic denervation in APP\/PS1 mice","volume":"72","author":"Ramos-Rodriguez","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/0006-8993(86)90904-2","article-title":"Learning impairment following lesion of the basal nucleus of Meynert in the marmoset: modification by cholinergic drugs","volume":"376","author":"Ridley","year":"1986","journal-title":"Brain Res."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.neurobiolaging.2012.05.019","article-title":"A noradrenergic theory of cognitive reserve: implications for Alzheimer\u2019s disease","volume":"34","author":"Robertson","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1002\/jnr.23667","article-title":"Effect of neurotrophin-3 precursor on glutamate-induced calcium homeostasis deregulation in rat cerebellum granule cells","volume":"93","author":"Safina","year":"2015","journal-title":"J. Neurosci. Res."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1152\/jn.00176.2006","article-title":"Two opposing roles of 4-AP-sensitive K+ current in initiation and invasion of spikes in rat mesencephalic trigeminal neurons","volume":"96","author":"Saito","year":"2006","journal-title":"J. Neurophysiol."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1038\/nn.3717","article-title":"Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase","volume":"17","author":"Sanchez-Padilla","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1016\/s0306-4522(98)00069-4","article-title":"The distribution of neurotrophin receptor TrkC-like immunoreactive fibers and varicosities in the rhesus monkey brain","volume":"86","author":"Sandell","year":"1998","journal-title":"Neuroscience"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/0165-3806(94)90306-9","article-title":"The development of neurotrophin receptor Trk immunoreactivity in the retina of the zebrafish (Brachydanio rerio)","volume":"81","author":"Sandell","year":"1994","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"13249","DOI":"10.1038\/ncomms13249","article-title":"Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer\u2019s pathology","volume":"7","author":"Schmitz","year":"2016","journal-title":"Nat. Commun."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.brainres.2011.05.026","article-title":"Direct projections from the central amygdaloid nucleus to the mesencephalic trigeminal nucleus in rats","volume":"1400","author":"Shirasu","year":"2011","journal-title":"Brain Res."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"8788","DOI":"10.1073\/pnas.92.19.8788","article-title":"Stress and antidepressants differentially regulate neurotrophin 3 mRNA expression in the locus coeruleus","volume":"92","author":"Smith","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.neures.2010.06.012","article-title":"The locus coeruleus projects to the mesencephalic trigeminal nucleus in rats","volume":"68","author":"Takahashi","year":"2010","journal-title":"Neurosci. Res."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"663","DOI":"10.3233\/ADR-220053","article-title":"Tooth loss induces memory impairment and glial activation in young wild-type mice","volume":"6","author":"Taslima","year":"2022","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/s0168-0102(02)00063-9","article-title":"Influence of tooth-loss and concomitant masticatory alterations on cholinergic neurons in rats: immunohistochemical and biochemical studies","volume":"43","author":"Terasawa","year":"2002","journal-title":"Neurosci. Res."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"11844","DOI":"10.1073\/pnas.91.25.11844","article-title":"Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons","volume":"91","author":"Tessarollo","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"re1","DOI":"10.1126\/sageke.2006.6.re1","article-title":"The development of amyloid \u03b2 protein deposits in the aged brain","volume":"2006","author":"Thal","year":"2006","journal-title":"Sci. Aging Knowl. Environ."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1002\/cne.10893","article-title":"Cellular interactions between axon terminals containing endogenous opioid peptides or corticotropin-releasing factor in the rat locus coeruleus and surrounding dorsal pontine tegmentum","volume":"466","author":"Tjoumakaris","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"114547","DOI":"10.1016\/j.bbr.2023.114547","article-title":"Increased vertical dimension of occlusion for varying periods differentially impairs learning and memory in guinea pigs","volume":"452","author":"Toyoda","year":"2023","journal-title":"Behav. Brain Res."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"841239","DOI":"10.3389\/fncel.2022.841239","article-title":"The nature of noradrenergic volume transmission from locus coeruleus to brainstem mesencephalic trigeminal sensory neurons","volume":"16","author":"Toyoda","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.1152\/jn.00997.2011","article-title":"Illusion caused by vibration of muscle spindles reveals an involvement of muscle spindle inputs in regulating isometric contraction of masseter muscles","volume":"108","author":"Tsukiboshi","year":"2012","journal-title":"J. Neurophysiol."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.3233\/JAD-160805","article-title":"Cholinergic basal forebrain lesion decreases neurotrophin signaling without affecting tau hyperphosphorylation in genetically susceptible mice","volume":"55","author":"Turnbull","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40478-017-0501-1","article-title":"Brainstem tau pathology in Alzheimer\u2019s disease is characterized by increase of three repeat tau and independent of amyloid beta","volume":"6","author":"Uematsu","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1523\/JNEUROSCI.08-03-01016.1988","article-title":"Corticotropin-releasing hormone increases tonic but not sensory-evoked activity of noradrenergic locus coeruleus neurons in unanesthetized rats","volume":"8","author":"Valentino","year":"1988","journal-title":"J. Neurosci."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/0006-8993(83)90615-7","article-title":"Corticotropin-releasing factor activates noradrenergic neurons of the locus coeruleus","volume":"270","author":"Valentino","year":"1983","journal-title":"Brain Res."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/s0306-4522(01)00279-2","article-title":"Corticotropin-releasing factor is preferentially colocalized with excitatory rather than inhibitory amino acids in axon terminals in the peri-locus coeruleus region","volume":"106","author":"Valentino","year":"2001","journal-title":"Neuroscience"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1046\/j.1365-2826.1998.00254.x","article-title":"Amygdaloid corticotropin-releasing factor targets locus coeruleus dendrites: substrate for the co-ordination of emotional and cognitive limbs of the stress response","volume":"10","author":"Van Bockstaele","year":"1998","journal-title":"J. Neuroendocrinol."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1097\/00005072-197909000-00004","article-title":"A quantitative study of the pigmented neurons in the nuclei locus coeruleus and subcoeruleus in man as related to aging","volume":"38","author":"Vijayashankar","year":"1979","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.bbi.2020.01.003","article-title":"Locus coeruleus neurons are most sensitive to chronic neuroinflammation-induced neurodegeneration","volume":"87","author":"Wang","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/ana.410100203","article-title":"Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis","volume":"10","author":"Whitehouse","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1126\/science.7058341","article-title":"Alzheimer\u2019s disease and senile dementia: loss of neurons in the basal forebrain","volume":"215","author":"Whitehouse","year":"1982","journal-title":"Science"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1002\/hipo.20440","article-title":"Effect of tooth loss on spatial memory and trkB-mRNA levels in rats","volume":"18","author":"Yamazaki","year":"2008","journal-title":"Hippocampus"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"4115","DOI":"10.1007\/s12035-017-0621-4","article-title":"The lesion analysis of cholinergic neurons in 5XFAD mouse model in the three-dimensional level of whole brain","volume":"55","author":"Yan","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1113\/jphysiol.2011.221051","article-title":"Action potential-triggered somatic exocytosis in mesencephalic trigeminal nucleus neurons in rat brain slices","volume":"590","author":"Zhang","year":"2012","journal-title":"J. Physiol."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"841133","DOI":"10.3389\/fncel.2022.841133","article-title":"Activation of the mesencephalic trigeminal nucleus contributes to masseter hyperactivity induced by chronic restraint stress","volume":"16","author":"Zhao","year":"2022","journal-title":"Front. Cell. 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