Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons

Geremia, Nicole M.; Pettersson, Lina; Hasmatali, Jovan C D; Hryciw, Todd; Danielsen, Nils; Schreyer, David J.; Verge, Valerie M. K.

doi:10.1016/j.expneurol.2009.07.022

Cited by 92 publications

(73 citation statements)

References 63 publications

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“…We believed that a positive retrograde signal initiated by PNS injury could relax the chromatin environment surrounding specific promoters and allow for gene expression; however, a negative signal following CNS injury may restrict promoter accessibility and inhibit gene expression. Following equidistant CNS (dorsal column axotomy, DCA) or PNS (sciatic nerve axotomy, SNA) axotomies, from L4-L6 DRG we assessed both high-throughput promoter and CGI DNA methylation (DNA methylation microarrays) and histone modifications (quantitative chromatin immunoprecipitation (ChIP) assays) at the proximal promoters of genes previously established to be critical to regeneration such as growth-associated protein 43 (GAP-43) 12 , Galanin 13 and brainderived neurotropic factor (BDNF) 14,15 (Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system

et al. 2014

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Section: Resultsmentioning

confidence: 99%

PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system

et al. 2014

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“…This death of neonatal motor neurons is in stark contrast to lower motor neurons that not only survive, but regenerate following adult sciatic nerve injury; sciatic injury has been shown to result in increased NGF, BDNF, IGFs, cilliary neurotrophic factor, and glial-derived neurotrophic factor secretion from Schwann cells [44][45][46][47][48][49][50][51][52][53]. Antibody depletion of Schwann cell-produced BDNF leads to decreased regeneration and deficits in myelination of lower motor neurons and sensory neurons [79][80][81].…”

Section: Neurotrophins Development and Survivalmentioning

confidence: 99%

“…Among the many changes activated by a conditioning lesion are increases in BDNF BDNF = brain-derived neurotrophic factor; NGF = nerve growth factor; NT-3 = neurotrophin-3; NT-4 = neurotrophin-4; 5-HT + = (serotonergic) raphaespinal; TH + (tyrosine hydroxylase expressing) coerulospinal expression. Indeed, blockade of BDNF both in vivo and in neuronal cultures attenuates neurite outgrowth after conditioning lesions [80,81]. Priming dorsal root ganglia with neurotrophins in vitro results in elevated cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activation, which similar to conditioning lesion attenuates the neurite outgrowth-inhibitory effects of central myelin [117].…”

Section: Intrinsic Capacity To Regeneratementioning

confidence: 99%

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Hollis

Tuszynski

2011

Neurotherapeutics

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Spinal cord injury permanently disrupts neuroanatomical circuitry and can result in severe functional deficits. These functional deficits, however, are not immutable and spontaneous recovery occurs in some patients. It is highly likely that this recovery is dependent upon spared tissue and the endogenous plasticity of the central nervous system. Neurotrophic factors are mediators of neuronal plasticity throughout development and into adulthood, affecting proliferation of neuronal precursors, neuronal survival, axonal growth, dendritic arborization and synapse formation. Neurotrophic factors are therefore excellent candidates for enhancing axonal plasticity and regeneration after spinal cord injury. Understanding growth factor effects on axonal growth and utilizing them to alter the intrinsic limitations on regenerative growth will provide potent tools for the development of translational therapeutic interventions for spinal cord injury.Keywords Neurotrophin . spinal cord injury . regeneration . axon plasticity . functional recovery Human Spinal Cord InjuryTraumatic injury of the spinal cord can produce a range of debilitating effects and permanently alter the capabilities and quality of life of its surviving victims. Damage to the central nervous system (CNS) in general results in destruction of neuronal circuitry. Contusion, compression, and penetration injuries of the spinal cord can interrupt the flow of sensory and motor information between the brain and periphery [1]. Depending on the location and severity of the injury, deficits can range from weakness of limb movement to total paralysis and ventilator-assisted respiration. Spontaneous functional recovery is limited, but can and often does occur in patients with initial sparing of sensorimotor function [2]. This recovery, which plateaus between 12 to 18 months, is very likely due to sparing and sprouting of axons within the zone of partial preservation, an area where some motor function remains intact, immediately adjacent to the lesion site [2].Approximately 40% of humans that sustain spinal cord injury (SCI) exhibit improvement from their early postinjury baseline, and this spontaneous recovery can range from modest to extensive [2]. Spontaneous recovery primarily appears to depend on the extent of tissue sparing at the injury site, allowing compensatory axonal sprouting and systems reorganization at levels ranging from the spinal cord to the cerebral cortex [3][4][5][6][7][8][9][10]. However, in cases of more severe injuries, means of enhancing endogenous levels of axonal sprouting and inducing true axonal regeneration are required to enhance functional outcomes.Electronic supplementary material The online version of this article

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“…4B) can activate the transcription of brain-derived neurotrophic factor (BDNF), a protein modulating synaptic plasticity related to memory, learning, and pain signaling (56,73,74). BDNF expression was found regulated by the neuronal growth factor NGF, a signaling pathway that was influenced by TPP2 (Supplemental Table III), and furthermore, BDNF expression correlates with neurite outgrowth (75,76). The latter can be linked to the observed rapid increase of neurite length in presence of TPP2 inhibition.…”

Section: Proteomic Changes By Tpp2 Inhibition and Knockmentioning

confidence: 99%

Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2

Wiemhoefer

Stargardt

Linden

et al. 2015

Molecular & Cellular Proteomics

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Tripeptidyl peptidase II (TPP2) is a serine peptidase involved in various biological processes, including antigen processing, cell growth, DNA repair, and neuropeptide mediated signaling. The underlying mechanisms of how a peptidase can influence this multitude of processes still remain unknown. We identified rapid proteomic changes in neuroblastoma cells following selective TPP2 inhibition using the known reversible inhibitor butabindide, as well as a new, more potent, and irreversible peptide phosphonate inhibitor. Our data show that TPP2 inhibition indirectly but rapidly decreases the levels of active, di-phosphorylated extracellular signal-regulated kinase 1 (ERK1) and ERK2 in the nucleus, thereby down-regulating signal transduction downstream of growth factors and mitogenic stimuli. We conclude that TPP2 mediates many important cellular functions by controlling ERK1 and ERK2 phosphorylation. For instance, we show that TPP2 inhibition of neurons in the hippocampus leads to an excessive strengthening of synapses, indicating that TPP2 activity is crucial for normal brain function. Molecular & Cellular

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Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons

Cited by 92 publications

References 63 publications

PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system

PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2

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