Recommended Conferences

Human Genetics and Genetic Disorders

Miami, USA

Tissue Engineering and Regenerative Medicine

Chicago, USA
Related Subjects
 

Chronic ciguatoxin treatment induces synaptic scaling through voltage gated sodium channels in cortical neurons

Author(s): Martin V, Vale C, Rubiolo JA, Roel M, Hirama M, et al.

Abstract

Ciguatoxins are sodium channels activators that cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents with long-term neurological alterations. In central neurons, chronic perturbations in activity induce homeostatic synaptic mechanisms that adjust the strength of excitatory synapses and modulate glutamate receptor expression in order to stabilize the overall activity. Immediate early genes, such as Arc and Egr1, are induced in response to activity changes and underlie the trafficking of glutamate receptors during neuronal homeostasis. To better understand the long lasting neurological consequences of ciguatera, it is important to establish the role that chronic changes in activity produced by ciguatoxins represent to central neurons. Here, the effect of a 30 min exposure of 10–13 days in vitro (DIV) cortical neurons to the synthetic ciguatoxin CTX 3C on Arc and Egr1 expression was evaluated using real-time polymerase chain reaction approaches. Since the toxin increased the mRNA levels of both Arc and Egr1, the effect of CTX 3C in NaV channels, membrane potential, firing activity, miniature excitatory postsynaptic currents (mEPSCs), and glutamate receptors expression in cortical neurons after a 24 h exposure was evaluated using electrophysiological and western blot approaches. The data presented here show that CTX 3C induced an upregulation of Arc and Egr1 that was prevented by previous coincubation of the neurons with the NaV channel blocker tetrodotoxin. In addition, chronic CTX 3C caused a concentration-dependent shift in the activation voltage of NaV channels to more negative potentials and produced membrane potential depolarization. Moreover, 24 h treatment of cortical neurons with 5 nM CTX 3C decreased neuronal firing and induced synaptic scaling mechanisms, as evidenced by a decrease in the amplitude of mEPSCs and downregulation in the protein level of glutamate receptors that was also prevented by tetrodotoxin. These findings identify an unanticipated role for ciguatoxin in the regulation of homeostatic plasticity in central neurons involving NaV channels and raise the possibility that some of the neurological symptoms of ciguatera might be explained by these compensatory mechanisms.

Similar Articles

Rat hippocampal neurons in dispersed cell culture

Author(s): Banker GA, Cowan WM

C1q induction and global complement pathway activation do not contribute to ALS toxicity in mutant SOD1 mice

Author(s): Lobsiger CS, Boillee S, Pozniak C, Khan AM, McAlonis-Downes M, et al.

A dramatic increase of C1q protein in the CNS during normal aging

Author(s): Stephan AH, Madison DV, Mateos JM, Fraser DA, Lovelett EA, et al.

When, where, and how much? Expression of the Kv3

Author(s): Gan L, Kaczmarek LK

Kv3

Author(s): Yasuda T, Cuny H, Adams DJ

A-type K+ channels encoded by Kv4

Author(s): Carrasquillo Y, Burkhalter A, Nerbonne JM

Functional specialization of the axon initial segment by isoform-specific sodium channel targeting

Author(s): Boiko T, van Wart A, Caldwell JH, Levinson SR, Trimmer JS, et al.

Role of axonal NaV1

Author(s): Royeck M, Horstmann MT, Remy S, Reitze M, Yaari Y, et al.

The role of the Rho GTPases in neuronal development

Author(s): GovekEE, Newey SE, van Aelst L

EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation

Author(s): Margolis SS, Salogiannis J, Lipton DM, Mandel-Brehm C, Wills ZP, et al.

Potential role of culture mediums for successful isolation and neuronal differentiation of amniotic fluid stem cells

Author(s): Orciani M, Emanuelli M, Martino C, Pugnaloni A, Tranquilli AL, et al.