Increased expression of Nogo‐A in hippocampal neurons of patients with temporal lobe epilepsy

Abstract

Mesial temporal lobe epilepsy (TLE) is associated with pronounced anatomical and biochemical changes in the hippocampal formation including extensive neurodegeneration, reorganization of mossy fibres and sprouting of interneurons. Although the anatomical features and some of the physiological consequences of hippocampal remodeling have been well documented, the molecular mechanisms underlying the profound and orientated outgrowth of hippocampal neurons in TLE are not yet understood. The reticulon protein Nogo-A has been associated with an inhibitory action on axon growth and plasticity. Using immunohistochemistry and in situ hybridization, we investigated the expression of Nogo-A in specimens obtained at surgery from patients with TLE compared with those obtained from autopsy controls. In control specimens, Nogo-A immunoreactivity and mRNA were mainly confined to oligodendrocytes. Only approximately 40% of the specimens revealed low expression of Nogo-A mRNA in neurons. In contrast, in TLE patients with and without Ammon's horn sclerosis, Nogo-A mRNA and immunoreactivity were markedly up-regulated in most neurons (3.6- and 4.4-fold increases in Nogo-A mRNA in granule cells of sclerotic and nonsclerotic specimens) and their processes throughout the hippocampal formation. Similar elevations in Nogo-A mRNA and protein levels were determined by quantitative RT-PCR and Western blotting. Since Nogo-A expression was also up-regulated in specimens without hippocampal sclerosis, it may be induced by seizures prior to progressing neurodegeneration.

Minocycline but not valproic acid influence the density of NogoA-immunoreactive neurons in the hilus of the dentate gyrus of the rats subjected to intracerebral haematoma

“…It is generally believed that NogoA expression in adult brain is characteristic for plastic CNS regions like cortex, dorsal root ganglia and of course hippocampus [28,30,34]. In human, increased immunoreactivity of NogoA-positive hippocampal neurons was observed in Alzheimer disease [9] and temporal lobe epilepsy [3]. The increase was also present in the experimental models of brain diseases including epilepsy [28,41] or brain injury [26,28,30].…”

Nogo enhances the adhesion of olfactory ensheathing cells and inhibits their migration

“…Meier et al showed that Nogo-A expression is upregulated after hippocampal denervation or kainate-induced seizures (Meier et al, 2003). Studies of Bandtlow et al (Bandtlow et al, 2004) demonstrated that Nogo-A mRNA and immunoreactivity are markedly increased in hippocampal neurons of patients with temporal lobe epilepsy. In the present study, Nogo-A was found highly expressed in OLs, which is Journal of Cell Science 120 (11) consistent with previous reports (Moreira et al, 1999;GrandPre et al, 2000;Huber et al, 2002).…”

Reticulons as Markers of Neurological Diseases: Focus on Amyotrophic Lateral Sclerosis

“…Although further investigation is needed, such genetic modifi cations may have functional signifi cance at least in a subset of patients. Finally, Nogo-A has been shown to be highly up-regulated in hippocampal neurons of patients with mesial temporal lobe epilepsy, which suggest its implication in the axonal sprouting and synaptic reorganization characteristic of the epileptic hippocampus [73] .…”