Altered glutamatergic tone reveals two distinct resting state networks at the cellular level in hippocampal sclerosis

Abstract

Hippocampal sclerosis (HS), the most common subset of drug-resistant epilepsy (DRE), is associated with large-scale network abnormalities, even under resting state. We studied the excitatory postsynaptic currents (EPSCs) recorded from pyramidal neurons in resected samples under resting conditions from the hippocampal and anterior temporal lobe (ATL) obtained from patients with HS (n = 14) undergoing resective surgery. We observed higher frequency and amplitude of spontaneous EPSCs in both the samples compared to non-seizure control samples. Application of tetrodotoxin (TTX) reduced the frequency of spontaneous EPSCs by 49.6 ± 4.3% and 61.8 ± 6.2% in the hippocampal and ATL samples, respectively. The magnitude of reduction caused by TTX with respect to non-seizure controls was significantly higher in the ATL samples than in the hippocampal samples. The magnitude of the change in the expression of the NR2A subunit of the NMDA receptors also varied in these two regions. Thus, the mechanism of hyperexcitabilty mediated by glutamatergic network reorganization in the hippocampal region is different from that in the ATL region of patients with HS, suggesting two independent resting-state networks at the cellular level. Taken together, these findings will improve the understanding of the broadly distributed resting-state networks in HS.

Comparative analysis of cytokine/chemokine regulatory networks in patients with hippocampal sclerosis (HS) and focal cortical dysplasia (FCD)

“…Alterations in cytokines and chemokines have been reported in tumor tissues and peripheral blood, but there are no reports showing chemokine/cytokinealterations inthe tumor periphery tissue. Owing to different limitations associated with autopsy, trauma and tumor periphery tissues, we preferred to use histopathologically normal tumor periphery tissues asnon-epileptic controlsfor this study, as suchnon-epileptic controls have been used previously in other studies 2 , 23 – 25 .…”

“…Since this condition can represent a potential problem in the evaluation of the tissue content of cytokines/chemokines/mRNA and microRNA in autopsy samples, brain tissues resected because of associated tumor pathologies would be more ideal to be considered as a non-epileptic control. Tissue taken from the perimeter of the abnormal area are also used as non-epileptic controls in previous studies 2 , 23 – 25 . 22 cortical tissues obtained from the margins of tumors during surgical resection (a part of the planned surgical resection) in patients with brain tumors without any history of seizures have been included as non-epileptic control (Table 1 ).…”

Genome-wide DNA Methylation and RNAseq Analyses Identify Aberrant Signalling Pathways in Focal Cortical Dysplasia (FCD) Type II

“…The resection was based on clinical evaluations and pathology was further verified by histopathologic examinations as described previously (Supplementary Fig. S2) 49 .…”

Chiral DNA sequences as commutable controls for clinical genomics

“…10c ). This omitted several notable false-positive mutations, such as a missense mutation ( G796V ) in the oncogene EGFR that confers resistance to the targeted anti-cancer drug gefitinib 44 . By applying the optimized thresholds determined using internal sequin controls to their accompanying patient samples, we retained 2–8 confident variants per patient (Fig.…”