Overexpression of inflammatory-related and nitric oxide synthase genes in olfactory bulbs from frontal lobe epilepsy patients.

Neuroinflammation has been shown to constitute a crucial mechanism in the pathophysiology of epileptic brain and several genes of inflammatory mediators have been detected in surgically resected hippocampus tissue but not in non-related seizure brain regions. Interestingly, it has been reported an olfactory dysfunction in frontal lobe epilepsy (FLE). Our aim was to quantify the gene expression of inflammatory-related and nitric oxide synthase genes in olfactory bulbs (OB) tissue from FLE patients. RNA was isolated from OB resection of FLE patients and autopsy subjects without any neurological disease (n = 7, each). After cDNA synthesis, we performed qPCR for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor κB p65 (RELA), Toll-like receptor 4 (TLR 4), its agonist high mobility group box 1 (HMGB 1) as well nitric oxide synthase isozymes (NOS 1, 2 and 3). We found a significant increase in gene expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNFα), TLR4 receptor and in its agonist HMGB1 and the downstream transcription factor NFκB p65. Moreover, we observed an increase of both NOS1 and NOS3 and a slightly increase of NOS2; however, it was not significant. Our study describes the overexpression of inflammatory-related genes and NOS isozymes in OB from FLE patients. Even though, the number of patients was limited, our findings could point out that neuroinflammation and nitrosative stress-related genes in the OB could be produced in general manner in all brain regions and thus contribute in part, to the olfactory dysfunction observed in FLE patients.

GABAergic alterations in neocortex of patients with pharmacoresistant temporal lobe epilepsy can explain the comorbidity of anxiety and depression: the potential impact of clinical factors.

Temporal lobe epilepsy (TLE) is a chronic neurodegenerative disease with a high prevalence of psychiatric disorders. Temporal neocortex contributes to either seizure propagation or generation in TLE, a situation that has been associated with alterations of the γ-amino-butyric acid (GABA) system. On the other hand, an impaired neurotransmission mediated by GABA in temporal neocortex has also been involved with the pathophysiology of psychiatric disorders. In spite of these situations, the role of the necortical GABA system in the comorbidity of TLE and mood disorders has not been investigated. The present study was designed to identify alterations in the GABA system such as binding to GABAA and GABAB receptors and benzodiazepine site, the tissue content of GABA and the expression of the mRNA encoding the α1-6, ß1-3, and γ GABAA subunits, in the temporal neocortex of surgically treated patients with TLE with and without anxiety, and/or depression. Neocortex of patients with TLE and comorbid anxiety and/or depression showed increased expression of the mRNA encoding the γ2-subunit, reduced GABAB-induced G-protein activation in spite of elevated GABAB binding, and lower tissue content of GABA when compared to autopsy controls. Some of these changes significantly correlated with seizure frequency and duration of epilepsy. The results obtained suggest a dysfunction of the GABAergic neurotransmission in temporal neocortex of patients with TLE and comorbid anxiety and/or depression that could be also influenced by clinical factors such as seizure frequency and duration of illness.