Research Article| Volume 216, P25-32, January 2019

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Nicotine is neuroprotective to neonatal neurons of sympathetic ganglion in rat

  • Author Footnotes
    1 Present Address: Department of Life Science, Bangalore University, Bengaluru 560056, India.
    Mahadevappa P. Badanavalu
    1 Present Address: Department of Life Science, Bangalore University, Bengaluru 560056, India.
    Department of Biological Sciences, Arkansas State University, Jonesboro, AR 72401, United States
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  • Malathi Srivatsan
    Corresponding author at: Department of Biological Sciences, 3712 Ridgeway Circle, Jonesboro, AR 72404, United States.
    Department of Biological Sciences, Arkansas State University, Jonesboro, AR 72401, United States
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  • Author Footnotes
    1 Present Address: Department of Life Science, Bangalore University, Bengaluru 560056, India.
Published:September 03, 2018DOI:


      • 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.


      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 NGF was withdrawn in rat neonatal SCG neuron cultures which were then treated with either 10 μM nicotine alone or with nAChR antagonists 0.1 μM α-bungarotoxin (antagonist for α7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.


      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)


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