CNS inflammation and bone marrow neuropathy in type 1 diabetes.
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.
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
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