Elsevier

Neuroscience

Volume 123, Issue 4, 2004, Pages 887-895
Neuroscience

Early increase of apoptosis-linked gene-2 interacting protein X in areas of kainate-induced neurodegeneration

https://doi.org/10.1016/j.neuroscience.2003.10.036Get rights and content

Abstract

Apoptosis-linked gene-2 interacting protein X (Alix) is thought to be involved in both cell death and vesicular trafficking. We examined Alix expression 2 h, 6 h and 24 h after triggering seizure-dependent neuronal death by i.p. kainic acid injection.

In the hippocampus, intense, transient immunolabelling was observed in the strata lucidum, oriens and radiatum, areas of high synaptic activity. The similarity of this distribution to those of synaptophysin and endophilin suggests a presynaptic localisation.

Alix labelling was increased in neuronal cell bodies in kainate-sensitive regions before or concomitant with the first signs of oedema and/or neuronal eosinophilia. The increase persisted 24 h after kainate-injection in CA3 and the piriform cortex which are areas with massive swelling and numerous pyknotic neurons. This suggests that Alix may play an early role in the mechanisms leading to cell death.

Taken together, our results suggest that Alix may be a molecular link between synaptic functioning and neuronal death.

Section snippets

KA treatment

Experiments were carried out in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC) and French law. All efforts were made to minimise the number of animals used and their suffering. Adult Sprague–Dawley rats (IFFA-CREDO, L'Arbresle, France) weighing about 250 g received a single i.p. injection of KA (1.2 mg/ml, Sigma-Aldrich Chimie SARL, St Quentin Fallavier, France) at 12.5 mg/kg or an equivalent volume of saline. After 2 h, animals were either killed or

Results

The present study describes the distribution of the protein Alix in normal and KA-treated rats. The behavioural modifications elicited by KA injection were mostly reproducible from one rat to another. Rats were first immobile, staring. After 30–40 min wet dog shakes could be observed with a frequency increasing with time. Masticatory movements, hypersalivation and rearing were observed later. Diazepam treatment stopped the seizures in KA-treated animals, whilst control rats went to sleep.

The

Discussion

Despite individual variations in response between rats, inherent to the KA paradigm, the present study clearly demonstrates three main findings. First, the protein Alix is minimally expressed in cell bodies and neuropil of the adult rat brain. Second, immunoreactivity in the neuropil is greatly increased in areas of intense synaptic activity, such as the strata oriens and radiatum 2 h after i.p. KA injection. Last, intense neuronal cell body labelling occurs in CA3 and the piriform lobe which

Acknowledgements

The authors are very grateful to Dr. P. de Camilli (Department of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven CT, USA) for the anti-endophilin and to Dr. V. Baille and Dr. P. Carpentier (Unité de Neurotoxicologie, CRSSA, Grenoble, France) for advice concerning fixation and histological procedures.

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