Distinct increased metabotropic glutamate receptor type 5 (mGluR5) in temporal lobe epilepsy with and without hippocampal sclerosis

Abstract

Metabotropic glutamate receptor type 5 (mGluR5) upregulation in temporal lobe epilepsy (TLE) and the correlation of its expression with features of hippocampal sclerosis (HS) remains unclear. Here we characterized mGluR5 immunoreactivity in hippocampus, entorhinal cortex (EC), and subiculum of TLE specimens with confirmed HS, with neocortical TLE (non-HS) and necropsy controls. We correlated mGluR5 immunoreactivity with neuronal density, mossy fiber sprouting, astrogliosis (GFAP), and dendritic alterations (MAP2). TLE specimens showed increased mGluR5 expression, which was most pronounced in the EC, subiculum, CA2, and dentate gyrus outer molecular layer. Increased mGluR5 expression was seen in hippocampal head and body segments and was independent of neuronal density, astrogliosis, or dendritic alterations. Positive correlation between mGluR5 expression with mossy fiber sprouting and with MAP2 in CA3 and CA1 was found only in HS specimens. Negative correlation between mGluR5 expression with seizure frequency and epilepsy duration was found only in non-HS cases. Specimens from HS patients without previous history of febrile seizure (FS) showed higher mGluR5 and MAP2 expression in CA2. Our study suggests that mGluR5 upregulation is part of a repertoire of post-synaptic adaptations that might control overexcitation and excessive glutamate release rather than a dysfunction that leads to seizure facilitation. That would explain why non-HS cases, on which seizures are likely to originate outside the hippocampal formation, also exhibit upregulated mGluR5. On the other hand, lower mGluR5 expression was related to increased seizure frequency. In addition to its role in hyperexcitability, mGluR5 upregulation could play a role in counterbalance mechanisms along the hyperexcitable circuitry uniquely altered in sclerotic hippocampal formation. Inefficient post-synaptic compensatory morphological (dendritic branching) and glutamatergic (mGluR5 expression) mechanisms in CA2 subfield could potentially underlie the association of FS with HS and TLE. © 2013 Wiley Periodicals, Inc.

Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia

“…Neuron density was then obtained according to Abercrombie's method (Abercombrie, 1946). Neuron density, as determined with Abercrombie method, is widely used in histopathological studies (Mathern et al, 1995a;Arthur-Farraj et al, 2012;Lee et al, 2012;Kandratavicius et al, 2013;Kandratavicius et al, 2014b), and gives similar results to stereological evaluation (Tramontin et al, 1998;Baquet et al, 2009). To examine the intensity of neo-Timm staining, we used a semi-quantitative scale for ranking mossy fiber gray intensity in the inner molecular layer of the DG (Tauck and Nadler, 1985).…”

Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits

“…All images were obtained with 200Â magnification under constant illumination (3 V, 60 ms exposure). The semi-quantitative analysis was performed by threshold tool with ImageJ 1.48 software (National Institutes of Health, USA), following published protocols (Kandratavicius et al, 2013;Wolf et al, 2016). Regions of interest comprised the prelimbic cortex (PL), basolateral nucleus of the amygdala (BLA), mediodorsal thalamic nucleus (MD), paraventricular thalamic nucleus (PVN), reuniens thalamic nucleus (Re), perirhinal cortex (PRh), entorhinal cortex (Ent), ectorhinal cortex (Ect), granular cell layer of hippocampus (DG), and pyramidal layer of hippocampus subfields (CA4, CA3, CA2, and CA1).…”

Neurotrophin receptors expression in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with seizure type and surgical outcome

“…Cell densities (neurons per cubic millimeter) were estimated in 8 μm Neu-N stained slices at 400x magnification with a morphometric grid methodology using Abercrombie's correction [50] as previously described and well established in the literature for surgical hippocampal fragments [3,[5][6][7][51][52][53][54][55].…”

“…A similar approach was used by our group elsewhere [6]. Results for granular layer included granular cell layer per se and proximal molecular layer.…”

“…Mesial temporal lobe epilepsy (MTLE), the most common cause of intractable epilepsy in adults, usually shows hippocampal sclerosis (HS), neuronal loss, gliosis and mossy fiber sprouting [3][4][5][6]. We have recently shown neuropathological data suggesting that there is a structural basis for psychiatric symptoms in the hippocampus of MTLE patients [7,8], and altered neurotrophin (NT) expression in presence of psychiatric comorbidities [9].…”