Neurotrophins regulate proliferation and survival of two microglial cell lines in vitro

Zhang, Jianmin; Geula, Changiz; Lu, Chengliang; Koziel, Henry; Hatcher, Linda M; Roisen, Fred J.

doi:10.1016/s0014-4886(03)00222-x

Cited by 96 publications

(78 citation statements)

References 61 publications

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“…Neurotrophins are a family of structurally and functionally related molecules, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, and NT-4/5. Neurotrophins have been shown to induce morphological changes and differentiation in neurons (Barbacid, 1994(Barbacid, , 1995Chao and Hempstead, 1995), they are released from microglia and regulate proliferation and morphological changes by autocrine-or paracrine-manner (Nakajima et al, 2001;Zhang et al, 2003). These earlier observations together with our present findings led us to suggest that Gmix may induce the release of neurotrophins from rat primary microglia and the released neurotrophins may then induce their ramified morphological changes.…”

Section: Discussionsupporting

confidence: 79%

GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro

Park¹,

Kim²,

Jou³

et al. 2008

Brain Research

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Section: Discussionsupporting

confidence: 79%

GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro

Park¹,

Kim²,

Jou³

et al. 2008

Brain Research

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“…Our data are supported by numerous reviews devoted to neuroprotective properties of BDNF (Cowansage et al, 2010;Géral et al, 2013;Khalin et al, 2015) and consistent with many experimental studies. In particular, a plethora of in vitro studies have demonstrated the neuroprotective potential of BNDF (Kume et al, 1997;Zhang et al, 2003;Liu et al, 2007;Casalbore et al, 2010;Zhu et al, 2011), showing that BDNF is also able to provide anti-apoptotic, anti-inflammatory and anti-neurotoxic actions that are essential for secondary TBI treatment. In addition, BDNF itself contributes to cognitive functions improving long-term memory (BlurtonJones et al, 2009) and was shown to improve working and reference memories in transient forebrain ischemia in rats (Kiprianova et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor delivered to the brain using poly (lactide-co-glycolide) nanoparticles improves neurological and cognitive outcome in mice with traumatic brain injury

et al. 2016

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(2016) Brain-derived neurotrophic factor delivered to the brain using poly (lactide-coglycolide) nanoparticles improves neurological and cognitive outcome in mice with traumatic brain injury, Drug Delivery, 23:9, 3520-3528, DOI: 10.1080/10717544.2016 Currently, traumatic brain injury (TBI) is the leading cause of death or disabilities in young individuals worldwide. The multi-complexity of its pathogenesis as well as impermeability of the blood-brain barrier (BBB) makes the drug choice and delivery very challenging. The brainderived neurotrophic factor (BDNF) regulates neuronal plasticity, neuronal cell growth, proliferation, cell survival and long-term memory. However, its short half-life and low BBB permeability are the main hurdles to be an effective therapeutic for TBI. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles coated by surfactant can enable the delivery of a variety of molecules across the BBB by receptor-mediated transcytosis. This study examines the ability of PLGA nanoparticles coated with poloxamer 188 (PX) to deliver BDNF into the brain and neuroprotective effects of BNDF in mice with TBI. C57bl/6 mice were subjected to weight-drop closed head injuries under anesthesia. Using enzyme-linked immunosorbent assay, we demonstrated that the intravenous (IV) injection of nanoparticle-bound BDNF coated by PX (NP-BDNF-PX) significantly increased BDNF levels in the brain of sham-operated mice (p50.001) and in both ipsi-(p50.001) and contralateral (p50.001) parts of brain in TBI mice compared to controls. This study also showed using the passive avoidance (PA) test, that IV injection of NP-BDNF-PX 3 h post-injury prolonged the latent time in mice with TBI thereby reversing cognitive deficits caused by brain trauma. Finally, neurological severity score test demonstrated that our compound efficiently reduced the scores at day 7 after the injury indicating the improvement of neurological deficit in animals with TBI. This study shows that PLGA nanoparticles coated with PX effectively delivered BDNF into the brain, and improved neurological and cognitive deficits in TBI mice, thereby providing a neuroprotective effect. KeywordsBlood-brain barrier, brain-derived neurotrophic factor, drug-delivery, nanoparticles, traumatic brain injury History

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“…BDNF can regulate the proliferation and survival of cultured microglia [21]. Mizoguchi et al demonstrated that BDNF could induce the sustained elevation of intracellular Ca 2+ in vitro [22].…”

Section: Discussionmentioning

confidence: 99%

Positive Feedback Loop of Autocrine BDNF from Microglia Causes Prolonged Microglia Activation

Zhang¹,

Zeng²,

Yu³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Microglia, which represent the immune cells of the central nervous system (CNS), have long been a subject of study in CNS disease research. Substantial evidence indicates that microglial activation functions as a strong neuro-inflammatory response in neuropathic pain, promoting the release of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α. In addition, activated microglia release brain-derived neurotrophic factor (BDNF), which acts as a powerful cytokine. In this study, we performed a series of in vitro experiments to examine whether a positive autocrine feedback loop existed between microglia-derived BDNF and subsequent microglial activation as well as the mechanisms underlying this positive feedback loop. Methods: Because ATP is a classic inducer of microglial activation, firstly, we examined ATP-activated microglia in the present study. Secondly, we used TrkB/Fc, the BDNF sequester, to eliminate the effects of endogenous BDNF. ATP-stimulated microglia without BDNF was examined. Finally, we used exogenous BDNF to further determine whether BDNF could directly activate BV2 microglia. In all experiments, to quantify BV2 microglia activation, the protein levels of CD11b, a microglial activation marker, were measured by western blot. A Transwell migration assay was used to examine microglial migration. To assess the synthesis and release of proinflammatory cytokines, western blot was used to measure BDNF synthesis, and ELISA was used to quantify TNF-α release. Results: In our present research, we have observed that ATP dramatically activates microglia, enhancing microglial migration, increasing the synthesis of BDNF and up-regulating the release of TNF-α. Microglial activation is inhibited following the sequestration of endogenous BDNF, resulting in impaired microglial migration and decreased TNF-α release. Furthermore, exogenous BDNF can also activate microglia to subsequently enhance migration and increase TNF-α release. Conclusion: Therefore, we suggest that microglial activation increases the synthesis of BDNF and that the release of BDNF can, in turn, activate microglia. A positive autocrine BDNF feedback loop from microglia may contribute to prolonged microglial activation.

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Neurotrophins regulate proliferation and survival of two microglial cell lines in vitro

Cited by 96 publications

References 61 publications

GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro

GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro

Brain-derived neurotrophic factor delivered to the brain using poly (lactide-co-glycolide) nanoparticles improves neurological and cognitive outcome in mice with traumatic brain injury

Positive Feedback Loop of Autocrine BDNF from Microglia Causes Prolonged Microglia Activation

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