The selective BDNF overexpression in neurons protects neuroglial networks against OGD and glutamate-induced excitotoxicity

Gaidin, Sergei G.; Turovskaya, M. V.; Gavrish, Maria S.; Бабаев, А.А.; Mal’tseva, V. N.; Blinova, Ekaterina; Turovsky, Egor A.

doi:10.1080/00207454.2019.1691205

Cited by 38 publications

(36 citation statements)

References 81 publications

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“…We have previously shown that BDNF is released by hippocampal cells under OGD and glutamate toxicity [22], and others have reported the same results [32]. We showed that the release of BDNF is a Ca 2?…”

Section: Vesicular Release Of Bdnf Mediates Its Neuroprotective Actiosupporting

confidence: 74%

“…We showed that the release of BDNF is a Ca 2? -dependent process that is suppressed by BafA1, a vacuolar ATPase inhibitor [22]. Incubation of (AAV)-Syn-BDNF-EGFP-transduced hippocampal cultures with BafA1 (1 lmol/L) for 24 h evoked a dramatic change in the basal expression of the genes encoding the vesicular glutamate transporters and subunits of GABA and glutamate receptors (Fig.…”

Section: Vesicular Release Of Bdnf Mediates Its Neuroprotective Actiomentioning

confidence: 98%

“…The chamber was placed on the microscope stage, and a grid-bordered area was randomly selected for fluorescent Ca 2? imaging. Then the cells were fixed and stained with antibodies according to the previously-described protocol [22]. Briefly, the cells were rinsed with Ca 2?…”

Section: Immunocytochemistrymentioning

confidence: 99%

“…The fluorescence of the probes was detected with an inverted fluorescence microscope (Zeiss Axio Observer Z1) using Filter Sets 01 and 20. Early and late apoptotic cells were discriminated using a previously-described method [22,27]. Five different areas in each culture were analyzed.…”

Section: Cell Viability Testmentioning

confidence: 99%

“…It regulates neurotransmission and cell survival via the activation of different receptors [21]. We have previously shown that BDNF overexpression alters the expression of genes that regulate neurotransmission, inflammation, and apoptosis, thus protecting hippocampal cells against death under oxygen-glucose deprivation (OGD) and glutamate toxicity [22].…”

Section: Introductionmentioning

confidence: 99%

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BDNF Overexpression Enhances the Preconditioning Effect of Brief Episodes of Hypoxia, Promoting Survival of GABAergic Neurons

et al. 2020

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Hypoxia causes depression of synaptic plasticity, hyperexcitation of neuronal networks, and the death of specific populations of neurons. However, brief episodes of hypoxia can promote the adaptation of cells. Hypoxic preconditioning is well manifested in glutamatergic neurons, while this adaptive mechanism is virtually suppressed in GABAergic neurons. Here, we show that brain-derived neurotrophic factor (BDNF) overexpression in neurons enhances the preconditioning effect of brief episodes of hypoxia. The amplitudes of the NMDAR-and AMPARmediated Ca 2? responses of glutamatergic and GABAergic neurons gradually decreased after repetitive brief hypoxia/ reoxygenation cycles in cell cultures transduced with the (AAV)-Syn-BDNF-EGFP virus construct. In contrast, the amplitudes of the responses of GABAergic neurons increased in non-transduced cultures after preconditioning. The decrease of the amplitudes in GABAergic neurons indicated the activation of mechanisms of hypoxic preconditioning. Preconditioning suppressed apoptotic or necrotic cell death. This effect was most pronounced in cultures with BDNF overexpression. Knockdown of BDNF abolished the effect of preconditioning and promoted the death of GABAergic neurons. Moreover, the expression of the anti-apoptotic genes Stat3, Socs3, and Bcl-xl substantially increased 24 h after hypoxic episodes in the transduced cultures compared to controls. The expression of genes encoding the pro-inflammatory cytokines IL-10 and IL-6 also increased. In turn, the expression of pro-apoptotic (Bax, Casp-3, and Fas) and proinflammatory (IL-1b and TNFa) genes decreased after hypoxic episodes in cultures with BDNF overexpression. Inhibition of vesicular BDNF release abolished its protective action targeting inhibition of the oxygen-glucose deprivation (OGD)-induced [Ca 2? ] i increase in GABAergic and glutamatergic neurons, thus promoting their death. Bafilomycin A1, Brefeldin A, and tetanus toxin suppressed vesicular release (including BDNF) and shifted the gene expression profile towards excitotoxicity, inflammation, and apoptosis. These inhibitors of vesicular release abolished the protective effects of hypoxic preconditioning in glutamatergic neurons 24 h after hypoxia/reoxygenation cycles. This finding indicates a significant contribution of vesicular BDNF release to the development of the mechanisms of hypoxic preconditioning. Thus, our results demonstrate that BDNF plays a pivotal role in the activation and enhancement of the preconditioning effect of brief episodes of hypoxia and promotes tolerance of the most vulnerable populations of GABAergic neurons to hypoxia/ischemia.

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Section: Vesicular Release Of Bdnf Mediates Its Neuroprotective Actiosupporting

confidence: 74%

Section: Vesicular Release Of Bdnf Mediates Its Neuroprotective Actiomentioning

confidence: 98%

Section: Immunocytochemistrymentioning

confidence: 99%

Section: Cell Viability Testmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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