title: Associations between xerostomia, histopathological alterations, and autonomic innervation of labial salivary glands in men in late midlife.
abstract: OBJECTIVE
  One aim of the present study was to investigate whether symptoms of oral dryness (xerostomia) during daytime, assessed in a study group of middle-aged male positive and negative outliers in cognition scores, were associated with age-related degenerative changes in human labial salivary glands and with quantitative measures of the glandular autonomic innervation. Another aim was to study the relation between the autonomic innervation and loss of secretory acinar cells in these glands.
  
  
  METHODS
  Labial salivary gland biopsies were taken from the lower lip from 190 men, born in 1953 and members of the Danish Metropolit birth cohort, who were examined for age-related changes in cognitive function and dental health as part of the Copenhagen University Center for Healthy Aging clinical neuroscience project. The glands were routinely processed and semi-quantitatively analyzed for inflammation, acinar atrophy, fibrosis, and adipocyte infiltration. Sections of labial salivary gland tissue were stained with the panneuronal marker PGP 9.5. In a subsample of 51 participants, the autonomic innervation of the glands was analyzed quantitatively by use of stereology.
  
  
  RESULTS
  Labial salivary gland tissue samples from 33% of all participants displayed moderate to severe acinar atrophy and fibrosis (31%). Xerostomia was not significantly associated with structural changes of labial salivary glands, but in the subsample it was inversely related to the total nerve length in the glandular connective tissue. Acinar atrophy and fibrosis were negatively correlated with the parenchymal innervation and positively related to diffuse inflammation.
  
  
  CONCLUSIONS
  The results from the present study indicate that aspects of the autonomic innervation of labial salivary glands may play a role in the occurrence of xerostomia which in the present study group was not significantly associated with degenerative changes in these glands. The findings further indicate that the integrity of labial salivary gland acini is related to the parenchymal autonomic innervation, whereas inflammatory processes may compromise it by alternative mechanisms.
authors.affiliation: Section of Oral Medicine, Clinical Oral Physiology, Oral Pathology and Anatomy, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Alle 20, 2200 Copenhagen, Denmark; Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. Electronic address: ches@sund.ku.dk.
authors.forename: Christiane Elisabeth
authors.initials: CE
authors.lastname: Sørensen
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Alle 20, 2200 Copenhagen, Denmark.
authors.forename: Jytte Overgaard
authors.initials: JO
authors.lastname: Larsen
authors.affiliation: Section of Oral Medicine, Clinical Oral Physiology, Oral Pathology and Anatomy, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Alle 20, 2200 Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Reibel
authors.affiliation: Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark; Department of Clinical Neurophysiology, Glostrup Hospital, Nordre Ringvej 57, 2600 Glostrup, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Lauritzen
authors.affiliation: Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Øster Farimagsgade 5A, 1353 Copenhagen, Denmark; Danish Aging Research Center, Universities of Aarhus, Southern Denmark and Copenhagen, J.B. Winsløwsvej 9, 5000 Odense C, Denmark.
authors.forename: Erik Lykke
authors.initials: EL
authors.lastname: Mortensen
authors.affiliation: Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Øster Farimagsgade 5A, 1353 Copenhagen, Denmark; Danish Aging Research Center, Universities of Aarhus, Southern Denmark and Copenhagen, J.B. Winsløwsvej 9, 5000 Odense C, Denmark; Research Center for Prevention and Health, Glostrup Hospital, Nordre Ringvej 57, 2600 Glostrup, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Osler
authors.affiliation: Section of Oral Medicine, Clinical Oral Physiology, Oral Pathology and Anatomy, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Alle 20, 2200 Copenhagen, Denmark; Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. Electronic address: amlp@sund.ku.dk.
authors.forename: Anne Marie Lynge
authors.initials: AM
authors.lastname: Pedersen
mesh_terms: D061354:Acinar Cells / Q000473:pathology; D000375:Aging / Q000473:pathology*; D017776:Autonomic Pathways / Q000473:pathology; D015331:Cohort Studies; D005355:Fibrosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000294:innervation / Q000473:pathology*; D014987:Xerostomia / Q000209:etiology / Q000473:pathology*
keywords: Autonomic innervation; Mucins; Salivary glands; Xerostomia