Basic fibroblast growth factor protects cerebellar neurons in primary culture from NMDA and non‐NMDA receptor mediated neurotoxicity

Fernández-Sánchez, Maria Teresa; Novelli, Antonello

doi:10.1016/0014-5793(93)80453-2

Cited by 77 publications

(36 citation statements)

References 38 publications

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“…If microglia are contributing to the enhancement of excitotoxicity, it is unlikely to be via activation of iNOS, because cultures lacking nNOS fail to exhibit neurotrophin-mediated enhancement of excitotoxic injury. When neurons are grown on a Poly-O matrix, BDNF pretreatment is neuroprotective, consistent with numerous previous reports of the protective role of neurotrophins (Mattson et al, 1989Fernandez-Sanchez and Novelli, 1993;Nozaki et al, 1993;Prehn et al, 1993;Burke et al, 1994;Lindholm, 1994;Lindvall et al, 1994;Nakao et al, 1995;Anderson et al, 1996). Thus, the phenotype of neuronal cultures is influenced markedly by the culture paradigm.…”

Section: Discussionsupporting

confidence: 72%

Differential Susceptibility to Neurotoxicity Mediated by Neurotrophins and Neuronal Nitric Oxide Synthase

Samdani¹,

Newcamp²,

Resink³

et al. 1997

J. Neurosci.

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NMDA neurotoxicity, which is mediated, in part, by formation of nitric oxide (NO) via activation of neuronal NO synthase (nNOS), is modulated by neurotrophins. nNOS expression in rat and mouse primary neuronal cultures grown on a glial feeder layer is significantly less than that of neurons grown on a polyornithine (Poly-O) matrix. Neurotrophins markedly increase the number of nNOS neurons, nNOS protein, and NOS catalytic activity and enhance NMDA neurotoxicity via NO-dependent mechanisms when neurons are grown on glial feeder layers. In contrast, when rat or mouse primary cortical neurons are grown on a Poly-O matrix, neurotrophins have no influence on nNOS neuronal number or NOS catalytic activity and reduce NMDA neurotoxicity. Primary neuronal cultures from mice lacking nNOS grown on a glial feeder layer fail to respond to neurotrophin-mediated enhancement of neurotoxicity. Together, these results indicate that nNOS expression and NMDA NO-mediated neurotoxicity are dependent, in part, on the culture paradigm, and neurotrophins regulate the susceptibility to NMDA neurotoxicity via modulation of nNOS. Furthermore, these results support the idea that NMDA neurotoxicity in culture is critically dependent on the developmental state of the neurons being assessed and suggest that, when cortical neurons are cultured on a glial feeder layer, they do not reach nearly as mature a phenotype as when grown on a Poly-O matrix.

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Section: Discussionsupporting

confidence: 72%

Differential Susceptibility to Neurotoxicity Mediated by Neurotrophins and Neuronal Nitric Oxide Synthase

Samdani¹,

Newcamp²,

Resink³

et al. 1997

J. Neurosci.

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“…This potential increase in vulnerability to apoptosis may be amplified by the dysregulation in growth factors we have observed in the same brains, particularly the FGF system (14). Indeed, it is conceivable that the dysregulation in growth factors plays a causative role in increased apoptosis and in the altered expression of glial-based glutamate transporters (38). In turn, because metabotropic glutamate receptors are coupled to G protein receptors and act on various second messenger systems, the effects could be even more far reaching through modulation of numerous downstream signaling mechanisms.…”

Section: Discussionmentioning

confidence: 76%

Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression

Choudary

Molnar

Evans

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

579

393

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Abnormalities in L-glutamic acid (glutamate) and GABA signal transmission have been postulated to play a role in depression, but little is known about the underlying molecular determinants and neural mechanisms. Microarray analysis of specific areas of cerebral cortex from individuals who had suffered from major depressive disorder demonstrated significant down-regulation of SLC1A2 and SLC1A3, two key members of the glutamate͞neutral amino acid transporter protein family, SLC1. Similarly, expression of L-glutamate-ammonia ligase, the enzyme that converts glutamate to nontoxic glutamine was significantly decreased. Together, these changes could elevate levels of extracellular glutamate considerably, which is potentially neurotoxic and can affect the efficiency of glutamate signaling. The astroglial distribution of the two glutamate transporters and L-glutamate-ammonia ligase strongly links glia to the pathophysiology of depression and challenges the conventional notion that depression is solely a neuronal disorder. The same cortical areas displayed concomitant up-regulation of several glutamate and GABA A receptor subunits, of which GABA A␣1 and GABAA␤3 showed selectivity for individuals who had died by suicide, indicating their potential utility as biomarkers of suicidality. These findings point to previously undiscovered molecular underpinnings of the pathophysiology of major depression and offer potentially new pharmacological targets for treating depression.bipolar disorder ͉ GABAA receptors ͉ glutamate transporters ͉ major depression ͉ suicide C linical depression, the phenotypic hallmark of the two leading mood disorders [major depressive disorder (MDD) and bipolar affective disorder (BPD)], is the most common psychiatric illness. It affects Ϸ121 million people worldwide, with 10-20% of women and 5-12% of men estimated to experience a depressive episode in any 1-year period, and with evidence of suicidality in 15% of those affected (ref.

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“…These findings contrast with those of previous reports, in which activation of the glutamate pathway led to upregulation of BDNF transcription in cerebellar granule neurons (Bessho, Nakanishi, & Nawa, 1993;Favaron et al, 1993;Lindholm, Dechant, Heisenberg, & Thoenen, 1993;Wu et al, 2004), which may be explained by the specificity of the transcription product targeted in this study. The increased levels of BDNF expression in these cases protected the cells from the toxic effects of excess glutamate; however, other studies have reported that administration of exogenous BDNF can prove either protective or detrimental to cells undergoing excitotoxic insults (Almeida et al, 2005;Brandoli et al, 1998;Cheng & Mattson, 1994;Fernández-Sánchez & Novelli, 1993;Koh, Gwag, Lobner, & Choi, 1995;Kume et al, 1997;Mattson et al, 1995;Prehn, 1996;Samdani et al, 1997;Skaper, Floreani, Negro, Facci, & Giusti, 1998). It will be important to ascertain whether the alteration in BDNF levels in these cells is a protective response, or part of the cascade of events leading to cell death.…”

Section: Discussionmentioning

confidence: 95%

Progesterone, BDNF and Neuroprotection in the Injured CNS

Coughlan

Gibson

Murphy

2009

International Journal of Neuroscience

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We investigated whether the neuroprotective mechanism of progesterone involves modulation of the neurotrophin brain-derived neurotrophic factor (BDNF). We show that BDNF expression is upregulated following cerebral ischemia in mice and in C6 glioma cells exposed to cytokines, while reduced in cerebellar granule neurons exposed to the excitotoxin glutamate. Progesterone was without additional effect on BDNF in these paradigms. Progesterone also protected PC12 neurons deprived of trophic support, while it decreased cerebellar granule neuron viability. Both the effects of progesterone and the expression of BDNF can clearly vary following stroke-like injuries, however we found no evidence for a neuroprotective relationship between progesterone and BDNF.

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Basic fibroblast growth factor protects cerebellar neurons in primary culture from NMDA and non‐NMDA receptor mediated neurotoxicity

Cited by 77 publications

References 38 publications

Differential Susceptibility to Neurotoxicity Mediated by Neurotrophins and Neuronal Nitric Oxide Synthase

Differential Susceptibility to Neurotoxicity Mediated by Neurotrophins and Neuronal Nitric Oxide Synthase

Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression

Progesterone, BDNF and Neuroprotection in the Injured CNS

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