BDNF: A missing link between sympathetic dysfunction and inflammatory disease?

Kasselman, Lora J.; Sideris, Alexandra; Bruno, Chantal; Perez, William R.; Cai, Na; Nicoletti, Jamee N.; Wiegand, Stanley J.; Croll, Susan D.

doi:10.1016/j.jneuroim.2006.03.008

Cited by 23 publications

(20 citation statements)

References 46 publications

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“…57 Interestingly, rs6265 is associated with differences in heart rate variability 29 and acute stress heart rate reactivity in healthy populations. 27 In fact, one study showed that local BDNF administration following surgical sympathectomy induced hippocampal vascular changes and edema 58 . This study suggests BDNF effects during a state of compromised autonomic function (e.g.…”

Section: Discussionmentioning

confidence: 99%

Variation in the BDNF Gene Interacts With Age to Predict Mortality in a Prospective, Longitudinal Cohort with Severe TBI

Failla

Kumar

Peitzman

et al. 2014

Neurorehabil Neural Repair

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Background Mortality predictions following traumatic brain injury (TBI) may be improved by including genetic risk in addition to traditional prognostic variables. One promising target is the gene coding for brain-derived neurotrophic factor (BDNF), a ubiquitous neurotrophin important for neuronal survival and neurogenesis. Objective We hypothesized the addition of BDNF genetic variation would improve mortality prediction models and that BDNF Met-carriers (rs6265) and C-carriers (rs7124442) would have the highest mortality rates post-TBI. Methods This study examined BDNF functional single nucleotide polymorphisms (SNPs) rs6265r (val66met) and rs7124442 (T>C) in relation to mortality in a prospective, longitudinal cohort with severe TBI. We examined 315 individuals receiving care for a closed head injury within the University of Pittsburgh Medical Center, aged 16–79. Mortality was examined acutely (0–7 days post-injury) and post-acutely (8–365 days post-injury). A gene risk score (GRS) was developed to examine both BDNF loci. Cox proportional hazards models were used to calculate hazard ratios for survivability post-TBI while controlling for covariates. Results BDNF GRS was significantly associated with acute mortality, regardless of age. Interestingly, subjects in the hypothesized no-risk allele group had the lowest survival probability. Post-acutely, BDNF-GRS interacted with age such that younger participants in the no-risk group had the highest survival probability, while older participants in the hypothesized no-risk group had the lowest probability of survival. Conclusions These data suggest complex relationships between BDNF and TBI mortality that interact with age to influence survival predictions beyond clinical variables alone. Evidence supporting dynamic, temporal balances of pro-survival/pro-apoptotic target receptors may explain injury and age-related gene associations.

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Section: Discussionmentioning

confidence: 99%

Variation in the BDNF Gene Interacts With Age to Predict Mortality in a Prospective, Longitudinal Cohort with Severe TBI

Failla

Kumar

Peitzman

et al. 2014

Neurorehabil Neural Repair

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“…Renal inflammation may result from primary sensory neurons that evoke neurogenic inflammation or from afferent transmission that probably includes brain-derived neurotrophic factor signaling, or overactivate sympathetic nerves. 16 As mentioned, the sympathetic neurotransmitter norepinephrine exerts pro-and anti-inflammatory properties. In hypertension, excessive sympathetic innervation may produce structural lesions in the kidney.…”

mentioning

confidence: 98%

Autonomic Renal Denervation Ameliorates Experimental Glomerulonephritis

Veelken

Vogel

Hilgers

et al. 2008

Journal of the American Society of Nephrology

100

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Increasing evidence indicates that inflammation of visceral organs is significantly affected by the autonomic nervous system. Such neuroimmune interactions have not been studied in the kidney. Here, we show that the rat kidney is innervated by both tyrosine hydroxylase-positive sympathetic efferent nerve fibers and calcitonin gene-related peptide-positive primary afferent nerve fibers, both of which are found in proximity to macrophages and dendritic cells. Complete surgical bilateral renal denervation was performed 2 d before glomerulonephritis was induced by injecting the monoclonal anti-Thy-1.1 antibody OX-7. Denervation significantly reduced albuminuria, mesangiolysis, formation of microaneurysms, deposition of glomerular collagen IV, and expression of TGF-␤ compared with sham-operated controls. Accordingly, inflammation, identified by accumulation of interstitial macrophages and renal expression of TNF-␣, and mesangial cell proliferation were significantly reduced. These findings indicate that autonomic renal denervation ameliorates and, by inference, innervation exacerbates acute inflammation in the kidney; therefore, neurotransmitters or neuropeptides and their receptors might represent novel targets for the treatment of acute glomerulonephritis.

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“…For example, data suggest that under conditions of sympathetic nervous system dysfunction, BDNF may have adverse effects within targets innervated by the sympathetic neurons. As evidence, BDNF induces perivascular inflammation in the hippocampus when sympathetic input to the hippocampus is reduced (Kasselman et al 2006). In a rat model of diabetic autonomic neuropathy characterized by the regular occurrence of pathologically distinctive dystrophic axons in prevertebral sympathetic ganglia and ileal mesenteric nerves, treatment with NGF exacerbated the pathology, suggesting that although deficiencies of neurotrophic factors may contribute to the pathogenesis of some neuropathies, excessively high levels of some neurotrophic factors may be detrimental (Schmidt et al 2001).…”

Section: Ans Dysfunction In Neurodegenerative and Psychiatric Disordersmentioning

confidence: 97%

Neurotrophic Factors in Autonomic Nervous System Plasticity and Dysfunction

Mattson

Wan

2008

Neuromol Med

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During development, neurotrophic factors are known to play important roles in regulating the survival of neurons in the autonomic nervous system (ANS) and the formation of their synaptic connectivity with their peripheral targets in the cardiovascular, digestive, and other organ systems. Emerging findings suggest that neurotrophic factors may also affect the functionality of the ANS during adult life and may, in part, mediate the effects of environmental factors such as exercise and dietary energy intake on ANS neurons and target cells. In this article, we describe the evidence that ANS neurons express receptors for multiple neurotrophic factors, and data suggesting that activation of those receptors can modify plasticity in the ANS. Neurotrophic factors that may regulate ANS function include brain-derived neurotrophic factor, nerve growth factor, insulin-like growth factors, and ciliary neurotrophic factor. The possibility that perturbed neurotrophic factor signaling is involved in the pathogenesis of ANS dysfunction in some neurological disorders is considered, together with implications for neurotrophic factor-based therapeutic interventions.

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BDNF: A missing link between sympathetic dysfunction and inflammatory disease?

Cited by 23 publications

References 46 publications

Variation in the BDNF Gene Interacts With Age to Predict Mortality in a Prospective, Longitudinal Cohort with Severe TBI

Variation in the BDNF Gene Interacts With Age to Predict Mortality in a Prospective, Longitudinal Cohort with Severe TBI

Autonomic Renal Denervation Ameliorates Experimental Glomerulonephritis

Neurotrophic Factors in Autonomic Nervous System Plasticity and Dysfunction

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