Transfection of C6 glioma cells with glia maturation factor upregulates brain-derived neurotrophic factor and nerve growth factor: trophic effects and protection against ethanol toxicity in cerebellar granule cells

Pantazis, Nicholas J.; Zaheer, Asgar; De, Dobbins; Zaheer, Smita; Green, Steven H.; Lim, Ramón

doi:10.1016/s0006-8993(00)02194-6

Cited by 31 publications

(12 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As exposure to insulin‐like growth factor‐1 (IGF‐1) inhibited both potassium‐withdrawal‐induced apoptosis (Gleichmann et al. 2000) and BDNF‐protected cerebellar granule neurons from ethanol toxicity (Pantazis et al. 2000) and as glutamate inhibition is protective in paradigms of neurotoxicity, we tested whether BDNF, or MK‐801, a non‐competitive NMDA‐receptor‐antagonist, were able to reduce cell death.…”

Section: Drug‐induced Cell Death Is Enhanced By Inhibition Of Akt Andmentioning

confidence: 99%

Chemotherapy‐induced cell death in primary cerebellar granule neurons but not in astrocytes: in vitro paradigm of differential neurotoxicity

Wick

Hirrlinger

Gerhardt³

et al. 2004

Journal of Neurochemistry

View full text Add to dashboard Cite

The nervous system is frequently the site of symptomatic toxicity of antineoplastic agents. However, there is limited information about the differential vulnerability of neurons, astrocytes and glioma cells. We have analyzed the effects of four chemotherapeutic drugs (lomustine, cisplatin, topotecan and vincristine) on primary cerebellar granule neurons and astrocytes derived from rats. All drugs led to cell death in cerebellar granule neurons in a concentration-dependent manner. Comparison of the EC 50 values for cerebellar neurons and astrocytes with the median EC 50 values of 12 malignant glioma cell lines demonstrated a large therapeutic range for lomustin and cisplatin. Further, this comparison revealed a 100-fold higher sensitivity of cerebellar neurons towards vincristine and 10-fold higher sensitivity towards topotecan compared with glioma cells. Astrocytes were generally resistant to vincristine. In cerebellar granule neurons, vincristine and to a lesser extent topotecan induced caspase 3 and caspase 9 cleavage, and enhanced caspase activity and Akt-dependent expression of phosphorylated BAD. 1 zVAD-fmk, a caspase inhibitor and brainderived neurotrophic factor (BDNF), but not MK-801, a noncompetitive NMDA receptor antagonist, significantly reduced vincristine-or topotecan-induced cell death.

show abstract

Section: Drug‐induced Cell Death Is Enhanced By Inhibition Of Akt Andmentioning

confidence: 99%

Chemotherapy‐induced cell death in primary cerebellar granule neurons but not in astrocytes: in vitro paradigm of differential neurotoxicity

Wick

Hirrlinger

Gerhardt³

et al. 2004

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…They form an endoneurial sheath, which acts as a guide for axonal growth from the proximal to the distal stumps. They also aid in clearing debris and creating a suitable environment for nerve regrowth (Heath and Rutkowski 1998;Ide 1996;Pantazis et al 2000). Schwann cells enhance the speed of electrical signals carried between the brain and the rest of the body (Bunge 1993;Tortora 1992).…”

Section: Introductionmentioning

confidence: 99%

Fabrication and evaluation of microgrooved polymers as peripheral nerve conduits

Hsu

Lu²,

Ni³

et al. 2007

Biomed Microdevices

View full text Add to dashboard Cite

Cell alignment plays an important role in the repair of damaged peripheral nerves. The aligned Schwann cells could direct the axonal outgrowth during nerve reconstruction. One way of aligning Schwann cells is to use surface grooves in micrometric dimensions. In this study, microgrooves on chitosan or poly(D,L-lactide) (PLA) were fabricated and the behaviors of Schwann cells and glial cell line C6 on these surfaces were examined. It was found that Schwann cells and C6 cells could be successfully aligned by the microgrooves, and express the genes related to the production of neurotrophic factors. The polymer conduits with microgrooves on the inner surface were implanted in rats to repair the damaged sciatic nerve. The microgrooved conduits were demonstrated to enhance peripheral nerve regeneration as compared to the smooth conduits.

show abstract

“…This neurotrophin is essential for normal Purkinje cell differentiation: In BDNF gene-deleted animals, Purkinje cell dendritic ramification is drastically abbreviated (Schwartz et al, 1997). In addition, BDNF has been shown to provide protection against ethanol neurotoxicity in a number of studies, with respect to several neuronal types (Mitchell et al, 1998(Mitchell et al, , 1999bBhave et al, 1999;Bradley et al, 1999;Pantazis et al, 2000). We hypothesized, therefore, that diminished access to this NTF would significantly exacerbate ethanol-mediated cell death during normally ethanol-resistant developmental periods.…”

Section: Introductionmentioning

confidence: 99%

Influence of ethanol on neonatal cerebellum of BDNF gene‐deleted animals: analyses of effects on Purkinje cells, apoptosis‐related proteins, and endogenous antioxidants

et al. 2002

View full text Add to dashboard Cite

The sensitivity of the developing central nervous system (CNS) to the deleterious effects of ethanol has been well documented, with exposure leading to a wide array of CNS abnormalities. Certain CNS regions are susceptible to ethanol during well-defined critical periods. In the neonatal rodent cerebellum, a profound loss of Purkinje cells is found when ethanol is administered early in the postnatal period [on postnatal days 4 or 5 (P4-5)], while this neuronal population is much less vulnerable to similar ethanol insult slightly later in the postnatal period (P7-9). Prior studies have shown that neurotrophic factors (NTFs) can be altered by ethanol exposure, and both in vitro and in vivo studies have provided evidence that such substances have the potential to protect against ethanol neurotoxicity. In the present study, it was hypothesized that depletion of an NTF shown to be important to cerebellar development would exacerbate ethanol-related effects within this region, when administration was confined to a normally ethanol-resistant ontogenetic period. For this study, brain-derived neurotrophic factor (BDNF) gene-deleted ("knockout") and wild-type mice were exposed to ethanol via vapor inhalation or to control conditions during the normally ethanol-resistant period (P7 and P8). Two hours after termination of exposure on P8, analyses were made of body weight, crown-rump length, and brain weight. In subsequent investigations, the number and density of Purkinje cells and the volume of cerebellar lobule I were determined, and the expression of anti- and pro-apoptotic proteins and the activities of endogenous antioxidants were assessed. It was found that the BDNF knockouts were significantly smaller than the wild-type animals, with smaller brain weights. Purkinje cell number and density was reduced in ethanol-treated knockout, but not wild-type animals, and the volume of lobule I was significantly decreased in the gene-deleted animals compared to wild-types, but was not further affected by ethanol treatment. The loss of Purkinje cells in the BDNF knockouts was accompanied by decreases in anti-apoptotic Bcl-xl and in phosphorylated (and hence inactivated) pro-apoptotic Bad, and reduced activity of the antioxidant glutathione reductase, while the antioxidant catalase was increased by ethanol treatment in this genotype. In the wild-type animals, anti-apoptotic Bcl-2 was decreased by ethanol treatment, but the pro-apoptotic c-Jun N-terminal kinase (JNK) was markedly diminished by ethanol exposure, while the activity of the protective antioxidant superoxide dismutase (SOD) was significantly enhanced. These results suggest that neurotrophic factors have the capacity to protect against ethanol neurotoxicity, perhaps by regulation of expression of molecules critical to neuronal survival such as elements of the apoptosis cascade and protective antioxidants.

show abstract

Transfection of C6 glioma cells with glia maturation factor upregulates brain-derived neurotrophic factor and nerve growth factor: trophic effects and protection against ethanol toxicity in cerebellar granule cells

Cited by 31 publications

References 71 publications

Chemotherapy‐induced cell death in primary cerebellar granule neurons but not in astrocytes: in vitro paradigm of differential neurotoxicity

Chemotherapy‐induced cell death in primary cerebellar granule neurons but not in astrocytes: in vitro paradigm of differential neurotoxicity

Fabrication and evaluation of microgrooved polymers as peripheral nerve conduits

Influence of ethanol on neonatal cerebellum of BDNF gene‐deleted animals: analyses of effects on Purkinje cells, apoptosis‐related proteins, and endogenous antioxidants

Contact Info

Product

Resources

About