Cocaine exposure impairs multilineage hematopoiesis of human hematopoietic progenitor cells mediated by the sigma-1 receptor

Abstract

Prenatal exposure to cocaine is a significant source of fetal and neonatal developmental defects. While cocaine associated neurological and cardiac pathologies are well-documented, it is apparent that cocaine use has far more diverse physiological effects. It is known that in some cell types, the sigma-1 receptor mediates many of cocaine's cellular effects. Here we present a novel and concise investigation into the mechanism that underlies cocaine associated hematopoietic pathology. Indeed, this is the first examination of the effects of cocaine on hematopoiesis. We show that cocaine impairs multilineage hematopoiesis from human progenitors from multiple donors and tissue types. We go on to present the first demonstration of the expression of the sigma-1 receptor in human CD34 + human hematopoietic stem/progenitor cells. Furthermore, we demonstrate that these cocaine-induced hematopoietic defects can be reversed through sigma-1 receptor blockade.

Cocaine Mediated Neuroinflammation: Role of Dysregulated Autophagy in Pericytes

“…Furthermore, the present study also validated the role of σ−1R in cocaine mediated induction of ER stress/ autophagy and inflammation. Role of σ−1R in cocaine mediated effects is in agreement with previously published findings [5,12,31,[62][63][64][65].…”

Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection

“…In contrast, knockout of sigma-1 receptors in mice suppressed neurite growth and the survival of newborn neuronal cells in the hippocampal dentate gyrus of adult mice [133]. Finally, stem cells which are under investigation for transplantation procedures [134] are enriched in sigma receptors [135]. …”

Anemia Burden, Types and Associated Risk Factors among Kenyan Human Immunodeficiency Virus-1 and Mycobacterium Tuberculosis Co-infected Injection Substance UsersAnemia Burden, Types and Associated Risk Factors among Kenyan Human Immunodeficiency Virus-1 a

“…This finding is corroborated with previous studies which have reported the majority of TB and HIV patients with normocytic normochromic and microcytic hypochromic anemias ( 11 , 43 , 44 ). Furthermore, heroin and cocaine have been shown to disrupt iron regulation and depress developmental potentials of hematopoietic stem cells ( 17 , 45 , 46 ). Contrarily, we found dominance of microcytic hypochromic anemia in HIV+ TB+ ISUs (43.8 %).…”

“…Anemia in HIV is further complicated by other comorbidities including injection substance use and TB ( 16 ). For instance, chronic use of methylamphetamine leads to severe aplastic anemia ( 17 ). In addition, cocaine and heroin use have been linked with iron deficiency anemia in HIV-1 infected females ( 18 , 19 ).…”