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Prenatal Cocaine Exposure Inhibits Neurite Outgrowth Through RAGE Pathway and Activates Altered Expression of Pro‐addictive Cytokines in Primary Neuronal and Glial Cell Cultures
Author(s) -
Johnson Marquita L,
Womble Tracy,
Jackson Tanise L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1175.6
Subject(s) - neurite , in utero , prenatal cocaine exposure , offspring , immunocytochemistry , endocrinology , biology , neuroglia , rage (emotion) , medicine , neuroscience , central nervous system , fetus , in vitro , pregnancy , prenatal exposure , biochemistry , genetics
Background The prevalence of neonates exposed to cociane continues to be an endemic within the U.S. An overwhelming amount of evidence has shown that prenatal cocaine exposure is associated with numerous neurological and behavioral abnormalities, as well as structural damage and a deficiency in neurodevelopment with no established underlying mechanisms. Purpose The present study was designed to investigate biochemical events coupled to cocaine‐induced cytotoxicity of neurons and glial cells seen in exposed offspring. Research Approach: Time pregnant Sprague‐Dawley rats were treated with 40 mg/kg of cocaine HCl on gestational day (GD) 10–21. On postnatal day (PND) 3 the brain tissue of the pups was harvested to yield mixed neuronal and glial cell cultures. A cytokine antibody array determined a decrease in RAGE expression and an increase in TIMP‐1 expression in prenatally exposed pups. Immunocytochemistry (ICC) showed decreased neurite outgrowth in prenatally exposed neurons. ICC also determined there was an increase in dopamine (DA) in prenatally exposed primary cell cultures indicating the presence of DA receptors on astrocytes and oligodendrocytes.. Western Blot analysis quantitatively determined a variation of amphoterin (HMGB1) which is necessary for RAGE activation and pro‐inflammatory cytokine matrix metalloproteinase 9 (MMP‐9) protein expressions between the control and cocaine treated pups. Conclusion Through in vivo and in vitro studies exposure to cocaine during gestation leads to marked alterations in morphology and function of primary neuronal and glial cell cultures. These findings suggest that exposure to cocaine in utero can ultimately increase the incidence of addiction and development of neurodegenerative diseases and neuropathologies in the affected offspring.