CNS inflammation and bone marrow neuropathy in type 1 diabetes

Ping Hu, Jeffrey S. Thinschmidt, Yuanqing Yan, Sugata Hazra, Ashay Bhatwadekar, Sergio Caballero, Tatiana Salazar, Jaleel A. Miyan, Wencheng Li, Andrei Derbenev, Andrea Zsombok, Maria Tikhonenko, James M. Dominguez, Susan P. McGorray, Daniel R. Saban, Michael E. Boulton, Julia V. Busik, Mohan K. Raizada, Tailoi Chan-Ling, Maria B. Grant

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1608-1620
Number of pages13
JournalAmerican Journal of Pathology
Volume183
Issue number5
DOIs
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Hu, P., Thinschmidt, J. S., Yan, Y., Hazra, S., Bhatwadekar, A., Caballero, S., Salazar, T., Miyan, J. A., Li, W., Derbenev, A., Zsombok, A., Tikhonenko, M., Dominguez, J. M., McGorray, S. P., Saban, D. R., Boulton, M. E., Busik, J. V., Raizada, M. K., Chan-Ling, T., & Grant, M. B. (2013). CNS inflammation and bone marrow neuropathy in type 1 diabetes. American Journal of Pathology, 183(5), 1608-1620. https://doi.org/10.1016/j.ajpath.2013.07.009