μ-Opioid Receptor Modulation of the Glutamatergic/GABAergic Midbrain Inputs to the Mouse Dorsal Hippocampus.

We used virus-mediated anterograde and retrograde tracing, optogenetic modulation, immunostaining, in situ hybridization, and patch-clamp recordings in acute brain slices to study the release mechanism and μ-opioid modulation of the dual glutamatergic/GABAergic inputs from the ventral tegmental area and supramammillary nucleus to the granule cells of the dorsal hippocampus of male and female mice. In keeping with previous reports showing that the two transmitters are released by separate active zones within the same terminals, we found that the short-term plasticity and pharmacological modulation of the glutamatergic and GABAergic currents are indistinguishable. We further found that glutamate and GABA release at these synapses are both virtually completely mediated by N- and P/Q-type calcium channels.

Therapeutic Potential of Low-Intensity Magnetic Field Stimulation in 6-Hydroxydopamine Rat Model of Parkinson's Disease: From Inflammation to Motor Function.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder that mainly affects the aged population. Transcranial magnetic field (MF) stimulation has shown to provide temporary motor recovery in neurological disorders.

Purpose: The aim of this study was to understand the cellular and molecular mechanism of low-intensity MF stimulation (17.

Novel variants in GABA receptor subunits: A possible association with benzodiazepine resistance in patients with drug-resistant epilepsy.

Benzodiazepines (BDZ) such as diazepam and lorazepam are popular as first-line treatment for acute seizures due to their rapid action and high efficacy. However, long-term usage of BDZ leads to benzodiazepine resistance, a phenomenon whose underlying mechanisms are still being investigated. One of the hypothesised mechanisms contributing to BDZ resistance is the presence of mutations in benzodiazepine-sensitive receptors.

Differential Levels of Tryptophan-Kynurenine Pathway Metabolites in the Hippocampus, Anterior Temporal Lobe, and Neocortex in an Animal Model of Temporal Lobe Epilepsy.

Glutamate-receptor-mediated hyperexcitability contributes to seizure generation in temporal lobe epilepsy (TLE). Tryptophan-kynurenine pathway (TKP) metabolites regulate glutamate receptor activity under physiological conditions. This study was designed to investigate alterations in the levels of TKP metabolites and the differential regulation of glutamatergic activity by TKP metabolites in the hippocampus, anterior temporal lobe (ATL), and neocortex samples of a lithium-pilocarpine rat model of TLE.

Differential glutamate receptor expression and function in the hippocampus, anterior temporal lobe and neocortex in a pilocarpine model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common form of intractable epilepsy where hyperactive glutamate receptors may contribute to the complex epileptogenic network hubs distributed among different regions. This study was designed to investigate the region-specific molecular alterations of the glutamate receptors and associated excitatory synaptic transmission in pilocarpine rat model of TLE. We recorded spontaneous excitatory postsynaptic currents (EPSCs) from pyramidal neurons in resected rat brain slices of the hippocampus, anterior temporal lobe (ATL) and neocortex.

Altered Spontaneous Glutamatergic and GABAergic Activity in the Peritumoral Cortex of Low-Grade Gliomas Presenting With History of Seizures.

The peritumoral regions of WHO grade II gliomas, like astrocytoma and oligodendroglioma, have been reported to show epileptiform activities. An imbalance of glutamatergic and GABAergic mechanisms is primarily responsible for the generation of epileptiform activities. Here we have compared the electrophysiological properties of pyramidal neurons in intraoperative peritumoral specimens obtained from glioma patients with (GS) and without (GN) a history of seizures at presentation.

Differential regulation of excitatory synaptic transmission in the hippocampus and anterior temporal lobe by cyclin dependent kinase 5 (Cdk5) in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).

Mesial temporal lobe epilepsy with hippocamapal sclerosis (MTLE-HS) is the most common form of drug resistant epilepsy (DRE). MTLE-HS is a distributed network disorder comprising of not only the hippocampus, but other anatomically related extrahippocampal regions. Excitatory synaptic transmission is differentially regulated in the hippocampal and extra-hippocampal regions of patients with MTLE-HS, but its mechanism not understood.

Increased levels of α4-containing GABA receptors in focal cortical dysplasia: A possible cause of benzodiazepine resistance.

Benzodiazepines are the first choice of anti-epileptic drugs used to treat seizures. However, it has been seen that their efficacy decreases with time leading to drug insensitivity, plausibly caused by an alteration in the expression of the benzodiazepine biding site on GABA receptors. This study was designed to investigate if the differential expression of GABA receptor subunits α1/α4/γ2/δ across the postsynaptic sites could contribute to benzodiazepine resistance in patients with focal cortical dysplasia (FCD), the most common cause of drug resistant epilepsy in pediatric population.

Altered hippocampal kynurenine pathway metabolism contributes to hyperexcitability in human mesial temporal lobe epilepsy-hippocampal sclerosis.

Background And Purpose: Glutamate receptor-mediated enhanced excitatory neurotransmission is typically associated with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Kynurenic acid and quinolinic acid are two important tryptophan-kynurenine pathway metabolites that modulate glutamate receptor activity. This study was designed to test the hypothesis that alteration in metabolism of tryptophan-kynurenine pathway metabolites in the hippocampus of patients with MTLE-HS contributes to abnormal glutamatergic transmission.

GABA Receptor-Mediated Epileptogenicity in Focal Cortical Dysplasia (FCD) Depends on Age at Epilepsy Onset.

Enhanced spontaneous GABA receptor activity is associated with focal cortical dysplasia (FCD), a developmental malformation of the cerebral cortex. Clinical manifestations in FCD vary with age at epilepsy onset with a more favorable prognosis in patients with late-onset (LO) compared to that in cases with early-onset (EO). This study was designed to test the hypothesis in FCD that spontaneous GABA receptor-mediated epileptogenicity depends on the age at epilepsy onset and varies between patients with early and late-onset age in FCD.

α7 nicotinic receptors contributes to glutamatergic activity in the hippocampus of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).

Hyperglutamatergic activity in the hippocampus is a major feature of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Here we investigated whether tonic α7 nicotinic receptor (nAChR) activity could contribute to enhanced glutamatergic activity in the hippocampus of patients with MTLE-HS. Results showed that frequency and amplitude of glutamatergic events recorded from pyramidal neurons in the hippocampal samples obtained from patients with MTLE-HS were altered by α7 nAChR antagonist, methyllycaconitine, suggesting α7 nAChRs may influence hyperexcitability in MTLE-HS.

Extremely low frequency magnetic field protects injured spinal cord from the microglia- and iron-induced tissue damage.

Spinal cord injury (SCI) is insult to the spinal cord, which results in loss of sensory and motor function below the level of injury. SCI results in both immediate mechanical damage and secondary tissue degeneration. Following traumatic insult, activated microglia release proinflammatory cytokines and excess iron due to hemorrhage, initiating oxidative stress that contributes to secondary degeneration.

Extremely low-frequency electromagnetic fields: A possible non-invasive therapeutic tool for spinal cord injury rehabilitation.

Traumatic insults to the spinal cord induce both immediate mechanical damage and subsequent tissue degeneration. The latter involves a range of events namely cellular disturbance, homeostatic imbalance, ionic and neurotransmitters derangement that ultimately result in loss of sensorimotor functions. The targets for improving function after spinal cord injury (SCI) are mainly directed toward limiting these secondary injury events.