Brain-derived neurotrophic factor protects neurons from GdCl3-induced impairment in neuron-astrocyte co-cultures

Abstract

Gadolinium (Gd 3+ ) complexes are important contrast agents in medical magnetic resonance imaging (MRI) and of great potential value in brain research. In order to better understand the mechanisms of the action of Gd 3+ on neurons in the complex central nervous system (CNS), the neurotoxic actions of GdCl 3 have been investigated in both neuron monoculture and astrocyteneuron co-culture systems. Measurements of lactate dehydrogenase release showed that GdCl 3 causes significant cell death of monocultured neurons as a result of reactive oxygen species (ROS) generation and down-regulation of brain-derived neurotrophic factor (BDNF). However, GdCl 3 does not affect the viability and BDNF expression of astrocytes. Both co-culturing of neurons with astrocytes and addition of BDNF ameliorated GdCl 3 -induced neurotoxicity by decreasing ROS generation and facilitating recovery of BDNF levels. The results obtained suggest that astrocytes in the CNS may protect neurons from GdCl 3 -induced impairment through secreting BDNF and thus up-regulating BDNF expression and interfering with Gd 3+ -induced cell signaling in neurons. A possible molecular mechanism is suggested which should be helpful in understanding the neurotoxic actions of gadolinium probes . gadolinium, brain-derived neurotrophic factor, BDNF, co-culture, astrocytes, neurons

Biological effects induced by Gadolinium nanoparticles on Lymphocyte A20 cell line

“…Feng X. et al have reported a remarkable increase in LDH leakage, after exposure of rat cortical neuron cells to GdCl 3 (0.2, 2, 20 and 100 µM) even at low micromolar doses (41). Almost in the same time, Xia Q. et al (42) revealed that GdCl 3 (0.2, 2, and 20 µM) induced in neurons a decrease of cell viability and an increase of LDH released onto the culture medium in a time-and concentration-dependent manner (43). Our data are not in accordance with these two studies, due to the fact that in our experiments Gd 3+ was firstly complexed by DOTA or DOTP and secondly embedded in the nanogels.…”

Gadolinium‐induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons

“…ER stress and oxidative stress also have been reported playing vital role in heavy metal-induced neurotoxicity (Erikson et al 2004;Biagioli et al 2008). Our previous study has revealed that oxidative stress was involved in the neurotoxicity of Gadolinium (Feng et al , 2011Xia et al 2010). Meanwhile, in another related research, we reported that Gadolinium could trigger ER stress in primary cultured rat cortical astrocytes (Feng et al , 2011.…”

“…Our previous study has revealed that oxidative stress was involved in the neurotoxicity of Gadolinium (Feng et al. 2010, 2011; Xia et al. 2010).…”

Neuroprotection by Manganese Superoxide Dismutase (MnSOD) Mimics: Antioxidant Effect and Oxidative Stress Regulation in Acute Experimental Stroke

“…Primary cortical neuronal cultures were prepared as described previously . Eighteen‐day‐old embryonic Sprague Dawley rats were sacrificed, and cortex tissues were obtained quickly.…”