title: CNS inflammation and bone marrow neuropathy in type 1 diabetes.
abstract: By using pseudorabies virus expressing green fluorescence protein, we found that efferent bone marrow-neural connections trace to sympathetic centers of the central nervous system in normal mice. However, this was markedly reduced in type 1 diabetes, suggesting a significant loss of bone marrow innervation. This loss of innervation was associated with a change in hematopoiesis toward generation of more monocytes and an altered diurnal release of monocytes in rodents and patients with type 1 diabetes. In the hypothalamus and granular insular cortex of mice with type 1 diabetes, bone marrow-derived microglia/macrophages were activated and found at a greater density than in controls. Infiltration of CD45(+)/CCR2(+)/GR-1(+)/Iba-1(+) bone marrow-derived monocytes into the hypothalamus could be mitigated by treatment with minocycline, an anti-inflammatory agent capable of crossing the blood-brain barrier. Our studies suggest that targeting central inflammation may facilitate management of microvascular complications.
authors.affiliation: Department of Anatomy, Bosch Institute, University of Sydney, Sydney, Australia.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Thinschmidt
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Yan
authors.forename: Sugata
authors.initials: S
authors.lastname: Hazra
authors.forename: Ashay
authors.initials: A
authors.lastname: Bhatwadekar
authors.forename: Sergio
authors.initials: S
authors.lastname: Caballero
authors.forename: Tatiana
authors.initials: T
authors.lastname: Salazar
authors.forename: Jaleel A
authors.initials: JA
authors.lastname: Miyan
authors.forename: Wencheng
authors.initials: W
authors.lastname: Li
authors.forename: Andrei
authors.initials: A
authors.lastname: Derbenev
authors.forename: Andrea
authors.initials: A
authors.lastname: Zsombok
authors.forename: Maria
authors.initials: M
authors.lastname: Tikhonenko
authors.forename: James M
authors.initials: JM
authors.lastname: Dominguez
authors.forename: Susan P
authors.initials: SP
authors.lastname: McGorray
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Saban
authors.forename: Michael E
authors.initials: ME
authors.lastname: Boulton
authors.forename: Julia V
authors.initials: JV
authors.lastname: Busik
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
authors.forename: Tailoi
authors.initials: T
authors.lastname: Chan-Ling
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000294:innervation* / Q000473:pathology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects; D011558:Herpesvirus 1, Suid / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008911:Minocycline / Q000494:pharmacology; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D018377:Neurotransmitter Agents; D016760:Proto-Oncogene Proteins c-fos; D049452:Green Fluorescent Proteins; D008911:Minocycline