let-7 MicroRNAs Regulate Microglial Function and Suppress Glioma Growth through Toll-Like Receptor 7.

Microglia express Toll-like receptors (TLRs) that sense pathogen- and host-derived factors, including single-stranded RNA. In the brain, let-7 microRNA (miRNA) family members are abundantly expressed, and some have recently been shown to serve as TLR7 ligands. We investigated whether let-7 miRNA family members differentially control microglia biology in health and disease.

The anticonvulsant lamotrigine enhances I in layer 2/3 neocortical pyramidal neurons of patients with pharmacoresistant epilepsy.

Alterations of the hyperpolarization activated nonselective cation current (I) are associated with epileptogenesis. Accordingly, the second-generation antiepileptic drug lamotrigine (LTG) enhances I in rodent hippocampus. We directly evaluated here whether LTG fails to enhance I in neocortical slices from patients with pharmacoresistant epilepsy.

Components of neuronal chloride transport in rat and human neocortex.

Considerable evidence indicates disturbances in the ionic gradient of GABAA receptor-mediated inhibition of neurones in human epileptogenic tissues. Two contending mechanisms have been proposed, reduced outward and increased inward Cl⁻ transporters. We investigated the properties of Cl⁻ transport in human and rat neocortical neurones (layer II/III) using intracellular recordings in slices of cortical tissue.

Evaluating reference genes to normalize gene expression in human epileptogenic brain tissues.

Several reference genes have been used to quantify gene expression in human epilepsy surgery tissue. However, their reliability has not been validated in detail, although this is crucial in interpreting epilepsy-related changes of gene expression. We evaluated 12 potential reference genes in neocortical tissues resected from patients with temporal lobe epilepsy (TLE) with either few or many seizures (n=6 each) and post mortem controls (n=6) using geNorm and NormFinder algorithms.

N-desmethylclozapine (NDMC) is an antagonist at the human native muscarinic M(1) receptor.

N-desmethylclozapine (NDMC) has been reported to display partial agonism at the human recombinant and rat native M(1) mAChR, a property suggested to contribute to the clinical efficacy of clozapine. However, the profile of action of NDMC at the human native M(1) mAChR has not been reported. The effect of NDMC on M(1) mAChR function was investigated in human native tissues by assessing its effect on (1) M(1) mAChR-mediated stimulation of [(35)S]-GTPgammaS-G(q/11)alpha binding to human post mortem cortical membranes and (2) the M(1) mAChR-mediated increase in neuronal firing in human neocortical slices.

Hyperpolarization-activated cation currents in human epileptogenic neocortex.

Purpose: Hyperpolarization-activated cation currents (I(H)) play a pivotal role in the control of neuronal excitability. In animal models of epilepsy both increases and decreases of I(H) have been reported. We, therefore, characterized properties of I(H) in human epileptogenic neocortex.

Impaired function of GABA(B) receptors in tissues from pharmacoresistant epilepsy patients.

Purpose: Effects of pre- and postsynaptic γ-aminobutyric acid B (GABA(B)) receptor activation were characterized in human tissue from epilepsy surgery.

Methods: Slices of human cortical tissue were investigated in a submerged-type chamber with intracellular recordings in layers II/III. Parallel experiments were performed in rat neocortical slices with identical methods.

Interlaminar differences of intrinsic properties of pyramidal neurons in the auditory cortex of mice.

Cortical information processing depends crucially upon intrinsic neuronal properties modulating a given synaptic input, in addition to integration of excitatory and inhibitory inputs. These intrinsic mechanisms are poorly understood in sensory cortex areas. We therefore investigated neuronal properties in slices of the auditory cortex (AC) of normal hearing mice using whole-cell patch-clamp recordings of pyramidal neurons in layers II/III, IV, V, and VI in the current- and voltage clamp mode.

Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.

Neuronal damage mediated by the TRAIL-system might be involved in the pathogenesis of neuroinflammatory diseases of the central nervous system. Here we used an investigator-independent approach to quantify TRAIL-mediated death of total CNS cells and neurons in a living human brain slice culture system, a model which is much closer to the in vivo situation than dissociated cell culture. We observed dose-dependent TRAIL-mediated death of both total human CNS cells and neurons, which was prevented by flupirtine-maleate, a centrally acting analgesic drug with proposed neuroprotective properties.

An impaired neocortical Ih is associated with enhanced excitability and absence epilepsy.

Neuronal subthreshold excitability and firing behaviour are markedly influenced by the activation and deactivation of the somato-dendritic hyperpolarization-activated cation current (Ih). Here, we evaluated possible contributions of Ih to hyperexcitability in an animal model of absence seizures (WAG/Rij rats). We investigated pyramidal neurons of the somatosensory neocortex, the site of generation of spike-wave discharges.