title: Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration.
abstract: Anticancer chemotherapy drugs challenge hematopoietic tissues to regenerate but commonly produce long-term sequelae. Chemotherapy-induced deficits in hematopoietic stem or stromal cell function have been described, but the mechanisms mediating hematopoietic dysfunction remain unclear. Administration of multiple cycles of cisplatin chemotherapy causes substantial sensory neuropathy. Here we demonstrate that chemotherapy-induced nerve injury in the bone marrow of mice is a crucial lesion impairing hematopoietic regeneration. Using pharmacological and genetic models, we show that the selective loss of adrenergic innervation in the bone marrow alters its regeneration after genotoxic insult. Sympathetic nerves in the marrow promote the survival of constituents of the stem cell niche that initiate recovery. Neuroprotection by deletion of Trp53 in sympathetic neurons or neuroregeneration by administration of 4-methylcatechol or glial-derived neurotrophic factor (GDNF) promotes hematopoietic recovery. These results demonstrate the potential benefit of adrenergic nerve protection for shielding hematopoietic niches from injury.
authors: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, New York, USA.
authors: Daniel
authors: D
authors: Lucas
authors: Christoph
authors: C
authors: Scheiermann
authors: Andrew
authors: A
authors: Chow
authors: Yuya
authors: Y
authors: Kunisaki
authors: Ingmar
authors: I
authors: Bruns
authors: Colleen
authors: C
authors: Barrick
authors: Lino
authors: L
authors: Tessarollo
authors: Paul S
authors: PS
authors: Frenette
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects* / Q000294:innervation; D002470:Cell Survival; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012038:Regeneration / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D011943:Receptors, Adrenergic, beta
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