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PLoS One. 2016 Aug 5;11(8):e0160585. doi: 10.1371/journal.pone.0160585. eCollection 2016.

Prenatal Cocaine Exposure Upregulates BDNF-TrkB Signaling.

Author information

1
Departments of Physiology, Pharmacology and Neuroscience, School of Medicine at CCNY, The City University of New York, New York, New York, 10031, United States of America.
2
Department of Biology, Neuroscience Program, Graduate School of The City University of New York, New York, New York, 10061, United States of America.

Abstract

Prenatal cocaine exposure causes profound changes in neurobehavior as well as synaptic function and structure with compromised glutamatergic transmission. Since synaptic health and glutamatergic activity are tightly regulated by brain-derived neurotrophic factor (BDNF) signaling through its cognate tyrosine receptor kinase B (TrkB), we hypothesized that prenatal cocaine exposure alters BDNF-TrkB signaling during brain development. Here we show prenatal cocaine exposure enhances BDNF-TrkB signaling in hippocampus and prefrontal cortex (PFCX) of 21-day-old rats without affecting the expression levels of TrkB, P75NTR, signaling molecules, NMDA receptor-NR1 subunit as well as proBDNF and BDNF. Prenatal cocaine exposure reduces activity-dependent proBDNF and BDNF release and elevates BDNF affinity for TrkB leading to increased tyrosine-phosphorylated TrkB, heightened Phospholipase C-γ1 and N-Shc/Shc recruitment and higher downstream PI3K and ERK activation in response to ex vivo BDNF. The augmented BDNF-TrkB signaling is accompanied by increases in association between activated TrkB and NMDARs. These data suggest that cocaine exposure during gestation upregulates BDNF-TrkB signaling and its interaction with NMDARs by increasing BDNF affinity, perhaps in an attempt to restore the diminished excitatory neurotransmission.

PMID:
27494324
PMCID:
PMC4975466
DOI:
10.1371/journal.pone.0160585
[Indexed for MEDLINE]
Free PMC Article

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