PMID- 23114219
OWN - NLM
STAT- MEDLINE
DCOM- 20130626
LR  - 20211021
IS  - 1522-1598 (Electronic)
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 109
IP  - 2
DP  - 2013 Jan
TI  - Neurotrophins regulate cholinergic synaptic transmission in cultured rat 
      sympathetic neurons through a p75-dependent mechanism.
PG  - 485-96
LID - 10.1152/jn.00076.2011 [doi]
AB  - The sympathetic nervous system regulates many essential physiological systems, 
      and its dysfunction is implicated in cardiovascular diseases. Mechanisms that 
      control the strength of sympathetic output are therefore potential targets for 
      the management of these disorders. Here we show that neurotrophins rapidly 
      potentiate cholinergic transmission between cultured rat sympathetic neurons. We 
      found that brain-derived neurotrophic factor (BDNF) and nerve growth factor 
      (NGF), acting at the p75 receptor, increased the amplitude of excitatory 
      postsynaptic currents (EPSCs). We observed increased amplitude but not frequency 
      of miniature synaptic currents after p75 activation, suggesting that p75 acts 
      postsynaptically to modulate transmission at these synapses. This neurotrophic 
      modulation enhances cholinergic EPSCs via sphingolipid signaling. Application of 
      sphingolactone-24, an inhibitor of neutral sphingomyelinase, blocked the effect 
      of BDNF, implicating a sphingolipid pathway. Furthermore, application of the 
      p75-associated sphingolipid second messengers C(2)-ceramide and 
      d-erythro-sphingosine restricted to the postsynaptic cell mimicked BDNF 
      application. Postsynaptic blockade of ceramide production with fumonisin, a 
      ceramide synthase inhibitor, blocked the effects of BDNF and 
      d-erythro-sphingosine, implicating ceramide or ceramide phosphate as the active 
      signal. Together these data suggest that neurotrophin signaling, which occurs in 
      vivo via release from sympathetic neurons and target tissues such as the heart, 
      acutely regulates the strength of the sympathetic postganglionic response to 
      central cholinergic inputs. This pathway provides a potential mechanism for 
      modulating the strength of sympathetic drive to target organs such as the heart 
      and could play a role in the development of cardiovascular diseases.
FAU - Luther, J A
AU  - Luther JA
AD  - Department of Biology, National Center for Behavioral Genomics, Brandeis 
      University, Waltham, Massachusetts 02454, USA.
FAU - Enes, J
AU  - Enes J
FAU - Birren, S J
AU  - Birren SJ
LA  - eng
GR  - P30 NS-45713/NS/NINDS NIH HHS/United States
GR  - R01 NS-057305/NS/NINDS NIH HHS/United States
GR  - R01 NS-066977/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121031
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Fumonisins)
RN  - 0 (N-acetylsphingosine)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism/*pharmacology
MH  - Cholinergic Neurons/*physiology
MH  - Coculture Techniques
MH  - Excitatory Postsynaptic Potentials/*drug effects
MH  - Fumonisins/pharmacology
MH  - Myocytes, Cardiac/physiology
MH  - Nerve Growth Factor/metabolism/*pharmacology
MH  - Rats
MH  - Receptor, Nerve Growth Factor/metabolism
MH  - Sphingosine/analogs & derivatives/pharmacology
MH  - Superior Cervical Ganglion/cytology/*physiology
PMC - PMC3545462
EDAT- 2012/11/02 06:00
MHDA- 2013/06/28 06:00
PMCR- 2014/01/15
CRDT- 2012/11/02 06:00
PHST- 2012/11/02 06:00 [entrez]
PHST- 2012/11/02 06:00 [pubmed]
PHST- 2013/06/28 06:00 [medline]
PHST- 2014/01/15 00:00 [pmc-release]
AID - jn.00076.2011 [pii]
AID - JN-00076-2011 [pii]
AID - 10.1152/jn.00076.2011 [doi]
PST - ppublish
SO  - J Neurophysiol. 2013 Jan;109(2):485-96. doi: 10.1152/jn.00076.2011. Epub 2012 Oct 
      31.