CNS inflammation and bone marrow neuropathy in type 1 diabetes.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Hu, P; Thinschmidt, JS; Yan, Y; Hazra, S; Bhatwadekar, A; Caballero, S; Salazar, T; Miyan, JA; Li, W; Derbenev, A; Zsombok, A; Tikhonenko, M; Dominguez, JM; McGorray, SP; Saban, DR; Boulton, ME; Busik, JV; Raizada, MK; Chan-Ling, T; Grant, MB
Published Date
- November 2013
Published In
Volume / Issue
- 183 / 5
Start / End Page
- 1608 - 1620
PubMed ID
- 24160325
Pubmed Central ID
- PMC3814523
Electronic International Standard Serial Number (EISSN)
- 1525-2191
Digital Object Identifier (DOI)
- 10.1016/j.ajpath.2013.07.009
Language
- eng
Conference Location
- United States