Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity

Calabrese, Francesca; Rossetti, A.C.; Racagni, Giorgio; Gass, Peter; Riva, Marco A.; Molteni, Raffaella

doi:10.3389/fncel.2014.00430

Cited by 395 publications

(280 citation statements)

References 97 publications

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“…It has important functions in brain development and plasticityrelated processes and it is a crucial neuromodulator in central nociceptive hypersensitivity [230,231]. ATP-mediated increased expression and/or cellular release has been demonstrated for BDNF in a variety of cell types.…”

Section: Growth Factorsmentioning

confidence: 99%

Extracellular ATP and other nucleotides—ubiquitous triggers of intercellular messenger release

Zimmermann

2015

Purinergic Signalling

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Extracellular nucleotides, and ATP in particular, are cellular signal substances involved in the control of numerous (patho)physiological mechanisms. They provoke nucleotide receptor-mediated mechanisms in select target cells. But nucleotides can considerably expand their range of action. They function as primary messengers in intercellular communication by stimulating the release of other extracellular messenger substances. These in turn activate additional cellular mechanisms through their own receptors. While this applies also to other extracellular messengers, its omnipresence in the vertebrate organism is an outstanding feature of nucleotide signaling. Intercellular messenger substances released by nucleotides include neurotransmitters, hormones, growth factors, a considerable variety of other proteins including enzymes, numerous cytokines, lipid mediators, nitric oxide, and reactive oxygen species. Moreover, nucleotides activate or co-activate growth factor receptors. In the case of hormone release, the initially paracrine or autocrine nucleotide-mediated signal spreads through to the entire organism. The examples highlighted in this commentary suggest that acting as ubiquitous triggers of intercellular messenger release is one of the major functional roles of extracellular nucleotides. While initiation of messenger release by nucleotides has been unraveled in many contexts, it may have been overlooked in others. It can be anticipated that additional nucleotide-driven messenger functions will be uncovered with relevance for both understanding physiology and development of therapy.

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Section: Growth Factorsmentioning

confidence: 99%

Extracellular ATP and other nucleotides—ubiquitous triggers of intercellular messenger release

Zimmermann

2015

Purinergic Signalling

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“…33 Future studies may analyze also the contribution of other factors, like brain-derived neurotrophic factor (BDNF) that was proposed as link between microglial activation and neuroplasticity. 36 On the other hand, a more differentiated view on microglia activation as potential therapeutic target ie, on the beneficial vs deleterious effects of minocycline is needed. We have to determine also the translational value of results obtained in the rodent model, before postulating cautiousness regarding the clinical use of tetracyclines.…”

mentioning

confidence: 99%

Microglia Activation and Schizophrenia: Lessons From the Effects of Minocycline on Postnatal Neurogenesis, Neuronal Survival and Synaptic Pruning

Inta

Lang

Borgwardt

et al. 2016

SCHBUL

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The implication of neuroinflammation in schizophrenia, sustained by recent genetic evidence, represents one of the most exciting topics in schizophrenia research. Drugs which inhibit microglia activation, especially the classical tetracycline antibiotic minocycline are currently under investigation as alternative antipsychotics. However, recent studies demonstrated that microglia activation is not only a hallmark of neuroinflammation, but plays important roles during brain development. Inhibition of microglia activation by minocycline was shown to induce extensive neuronal cell death and to impair subventricular zone (SVZ) neurogenesis and synaptic pruning in the early postnatal and adolescent rodent brain, respectively. These deleterious effects contrast with the neuroprotective actions of minocycline at adult stages. They are of potential importance for schizophrenia, since minocycline triggers similar pro-apoptotic effects in the developing brain as NMDA receptor (NMDAR) antagonists, known to induce long-term schizophrenia-like abnormalities. Moreover, altered postnatal neurogenesis, recently described in the human striatum, was proposed to induce striatal dopamine dysregulation associated with schizophrenia. Finally, the effect of minocycline on synapse remodeling is of interest considering the recently reported strong genetic association of the pruning-regulating complement factor gene C4A with schizophrenia. This raises the exciting possibility that in conditions of hyperactive synaptic pruning, as supposed in schizophrenia, the inhibitory action of minocycline turns into a beneficial effect, with relevance for early therapeutic interventions. Altogether, these data support a differential view on microglia activation and its inhibition. Further studies are needed to clarify the relevance of these results for the pathogenesis of schizophrenia and the use of minocycline as antipsychotic drug.Key words: minocycline/apoptosis/postnatal neurogenesis/subventricular zone/synaptic pruning/early therapy More than 30 years ago signs of low-grade inflammation had been found post-mortem in brains of patients with schizophrenia.

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“…45,46 Previous research has shown that neurotrophins, as a bridge between the immune system and neuroplasticity, results from the integration of multiple mechanisms. 47 BCG vaccination has long been known to be a potent inducer of IFN-g-secreting Th1 responses and Tregs. 15,48,49 The increase in the levels of circulating immune factors (e.g., cytokines, chemokines or other factors), many of which can enter the CNS.…”

Section: Discussionmentioning

confidence: 99%

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

Zhang

Zou

et al. 2015

Human Vaccines & Immunotherapeutics

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y These authors equally contributed to this work.Keywords: dendritic complexity, fractal dimension, neurotrophin, spine, sholl analysis Abbreviations: BCG, Bacillus Calmette-Gu erin; CNS, central nevers system; BDNF, brain derived neurotrophic factor; IGF-1, insulin-like growth factor 1; AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptorDendritic structure is sensitive to changes in the environment during brain development. Accumulating evidence has demonstrated that early immune activation can significantly affect neuronal development. Our study concentrated on the morphological study of neural dendrites and spines in the hippocampal CA1 area using Diolistic labeling with Sholl analysis and fractal analysis. The results revealed that Bacille Calmette-Gu erin (BCG) vaccination enhanced dendritic complexity, as reflected by the increased number of intersections, number of branch points and fractal dimension, and promoted neurite outgrowth. In addition, BCG increased the density and promoted the maturation of dendritic spines. The alterations in dendritic structure and spine morphology were observed at 2 and 4 w, but the differences were more apparent at 4 w than at 2 w. However, no significant difference was observed at 8 w. Furthermore, we observed that BCG increased the expression of hippocampal brain derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). Hippocampal BDNF/IGF-1 was positively correlated with apical dendritic length, fractal dimension, and spine density. Taken together, we show in this study that neonatal BCG vaccination promotes dendritic development in developing hippocampal CA1 neurons, most likely by increasing the expression of BDNF and IGF-1 in the hippocampus.

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Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity

Cited by 395 publications

References 97 publications

Extracellular ATP and other nucleotides—ubiquitous triggers of intercellular messenger release

Extracellular ATP and other nucleotides—ubiquitous triggers of intercellular messenger release

Microglia Activation and Schizophrenia: Lessons From the Effects of Minocycline on Postnatal Neurogenesis, Neuronal Survival and Synaptic Pruning

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

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