BDNF: a missing link between sympathetic dysfunction and inflammatory disease?
Nerve growth factor (NGF) plays a role in sympathetic neuron integrity and survival. Brain-derived neurotrophic factor (BDNF) also has trophic effects on sympathetic neurons. We report here the serendipitous finding that co-treatment of hippocampus with BDNF and the NGF antagonist TrkA-Fc leads to perivascular inflammation and marked vasoconstriction. This effect is not observed with either reagent alone or in combination with other control proteins. Because NGF supports sympathetic neuron health, we tested the hypothesis that BDNF combined with sympathetic compromise caused this effect. Superior cervical ganglia were removed bilaterally with concurrent BDNF infusion into hippocampus. Perivascular inflammation was observed at 3 days, but not 12 days post treatment, when sympathetic terminals had receded, suggesting that the presence of these terminals was necessary for inflammation. Since sympathetic dysfunction may lead to compensatory overactivity of norepinephrine (NE) signaling, we co-infused BDNF with NE in the hippocampus and observed perivascular inflammation. In humans, sympathetic overactivity has been reported in a variety of vascular diseases. Some of these diseases, e.g. primary Raynaud's, are not accompanied by serious inflammatory disease whereas others, such as scleroderma and systemic lupus, are. We speculate that BDNF may contribute to the transformation of sympathetic dysfunction to inflammatory disease.
Kasselman
Lora J
LJ
Neuropsychology Doctoral Subprogram, Graduate Center of the City University of New York, USA.
Sideris
Alexandra
A
Bruno
Chantal
C
Perez
William R
WR
Cai
Ning
N
Nicoletti
Jamee N
JN
Wiegand
Stanley J
SJ
Croll
Susan D
SD
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007260:Infusion Pumps; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor