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|Title:||CERAMIDE REGULATION OF SYNAPTIC TRANSMISSION IN AREA CA1 OF THE HIPPOCAMPUS|
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|Authors/Affiliations:||1 Christian Patenaude*; 1 Guy Massicotte; |
1 Université du Québec à Trois-Rivières. QC, Canada
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|Content:||Objectives: Ceramides are major components of plasma membranes which also act as lipid mediators that regulate several neuronal processes, including growth, differentiation, apoptosis and survival. Functionally, ceramides have been shown to alter neuronal excitability by modulating several voltage-gated channels, are involved in NGF-mediated increase in glutamate release during development, and can modify the surface expression of acetylcholine receptors in cell lines. However, much less is known about the influence of ceramides on synaptic transmission in the brain. Experiments were therefore undertaken to investigate how these bioactive lipids affect GABAergic, glutamatergic and cholinergic neurotransmitter systems in the hippocampus.|
Materials and Methods: Hippocampal slices were prepared from 3-5 week-old rats and incubated for at least 3 h in oxygenated ACSF containing vehicle, a synthetic ceramide analog or bacterial sphingomyelinase (SMase), which triggers the generation of endogenous ceramides. Patch-clamp whole-cell recordings were then carried on CA1 pyramidal cells in the presence of appropriate synaptic receptor antagonists to record spontaneous excitatory (sEPSCs) or inhibitory (sIPSCs) postsynaptic currents from control and treated slices.
Results: Pyramidal cells exposed to C8-ceramide showed a dramatic decrease in sEPSC frequency compared to control cells, while the amplitude was unaffected. Similarly, a reduction in sEPSC frequency, but not amplitude, was observed in slices incubated with SMase, indicating that the effects of endogenously-generated and exogenously-applied ceramides were comparable. In contrast, slices treated with C8-ceramide did not exhibit any changes in sIPSC frequency and amplitude relative to control slices. Interestingly, the robust increase in sIPSC frequency, amplitude and total charge transfer elicited by the muscarinic receptor agonist pilocarpine in vehicle-treated slices was abolished in slices incubated with C8-ceramide.
Conclusion: These results suggest that ceramides selectively modulate glutamate and acetylcholine synaptic transmission in the hippocampus, while GABAergic neurotransmission remains unaffected. Given that ceramides can be generated under noxious conditions such as inflammation and oxidative stress, these lipid mediators are likely to contribute to synaptic alterations encountered in these circumstances.
This work was supported by NSERC.
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