Highlights
- •NGF withdrawal for 48h led to apoptosis in SCG neurons with increased TUNEL positive cells and decreased cell survival.
- •Treatment of SCG neurons with 10 μM nicotine protected them from cell death resulting from NGF withdrawal.
- •Increased expression of ERK1/2 indicated that nicotine exposure may activate survival signaling kinases in SCG neurons.
- •Use of nicotinic receptor blockers suggested that nicotine mediated neuroprotection was through both α7 and α3 nAChRs.
- •Thus pre and perinatal exposure to nicotine can interfere with programmed cell death in developing sympathetic neurons.
Abstract
Sympathetic neurons of SCG are dependent on availability of nerve growth factor (NGF)
for their survival. SCG neurons express nicotinic receptors (nAChR) whose expression
levels are modulated by nicotine. Nicotine exerts multiple effects on neurons, including
neuroprotection, through nAChR binding. Although sympathetic neurons express robust
levels of nAChR, a possible neuroprotective role for nicotine in these neurons is
not well-understood. Therefore we determined the effect of nicotine exposure on survival
of SCG neurons during NGF withdrawal in a well-established cell culture system. NGF
was withdrawn in rat neonatal SCG neuron cultures which were then treated with either
10 μM nicotine alone or with nAChR antagonists 0.1 μM α-bungarotoxin (antagonist for
α7 subunit bearing nAChR) and 10 μM mecamylamine (non-specific antagonist for ganglionic
nAChR) for 48 h. Apoptotic death was determined by TUNEL staining. Cell survival was
also determined by MTS assay. Western blot analysis of ERK1/2 was also performed.
Our results showed that exposure to 10 μM nicotine significantly reduced apoptotic
cell death in SCG neurons resulting from NGF withdrawal as shown by fewer TUNEL positive
cells. The MTS assay results also revealed that 10 μM nicotine concentration significantly
increased cell survival thus indicating neuroprotective effect of nicotine against
cell death resulting from NGF withdrawal. Nicotinic receptor antagonists (bungarotoxin
& mecamylamine) attenuated the effect of nicotine's action of neuroprotection. Western
blot analysis showed an increased expression of ERK1/2 in nicotine treated cultures
suggesting nicotine provided neuroprotection in SCG neurons by increasing the expression
of ERK1/2 through nicotinic receptor dependent mechanisms.
Abbreviations:
ERK1/2 (extracellular signal-regulated kinases), MTS (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide), SCG (superior cervical ganglion), TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP-biotin Nick End Labeling)Keywords
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Article info
Publication history
Published online: September 03, 2018
Accepted:
August 31,
2018
Received in revised form:
July 13,
2018
Received:
May 11,
2018
Identification
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© 2018 Elsevier B.V. All rights reserved.
