Glial glutamate transporter GLT1 plays a key role in the maintenance of extracellular glutamate homeostasis. Recent human genetic studies have suggested that de novo mutations in GLT1 (EAAT2) cause early-onset epilepsy with multiple seizure types. Consistent with these findings, global GLT1 null mice show lethal spontaneous seizures. The consequences of GLT1 dysfunction vary between different brain regions, suggesting that the role of GLT1 dysfunction in epilepsy may also vary with brain regions. In this study, we generated region-specific GLT1 knockout mice by crossing floxed-GLT1 mice with mice that express the Cre recombinase in a particular domain of the ventricular zone. Selective deletion of GLT1 in the diencephalon, brainstem and spinal cord is sufficient to reproduce the phenotypes (excess mortality, decreased body weight, and lethal spontaneous seizure) of the global GLT1 null mice. By contrast, dorsal forebrain-specific GLT1 knockout mice showed nonlethal complex seizures including myoclonic jerks, hyperkinetic running, spasm and clonic convulsion via the activation of NMDA receptors during a limited period from P12 to P14 and selective neuronal death in cortical layer II/III and the hippocampus. Thus, GLT1 dysfunction in the dorsal forebrain is involved in the pathogenesis of infantile epilepsy and GLT1 in the diencephalon, brainstem and spinal cord may play a critical role in preventing seizure-induced sudden death.

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In patients with Parkinson’s disease (PD), non-motor symptoms (NMS) including depression and anxiety are often recognized before motor symptoms develop. Monoamine oxidase (MAO)-B inhibitors are therapeutically effective for motor symptoms; however, their effects on NMS in PD are yet to be fully assessed. Here, we aimed to explore the antidepressant-like effects of propargyl MAO-B inhibitors, selegiline and rasagiline, in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a PD model, and to elucidate the mechanisms underlying these effects. Four repeated intraperitoneal injections of MPTP at 17.5 mg/kg to C57BL/6 mice led to a partial reduction in the number of nigrostriatal tyrosine hydroxylase-positive neurons and to the extension of immobility time during the tail suspension test (TST), without any obvious induction of motor deficits. A single subcutaneous administration of selegiline at 10 mg/kg shortened the extended immobility time of MPTP mice in the TST, without any increase in motor activities, suggesting that selegiline exerts antidepressant-like effects. In this test, rasagiline did not produce antidepressant-like effects, although the inhibitory effect of 3 mg/kg rasagiline on brain MAO activity was comparable to that of 10 mg/kg selegiline. The shortened immobility time in the TST correlated with reduced cortical dopamine (DA) turnover rates in MPTP mice treated with selegiline, but not in MPTP mice treated with rasagiline. These results suggest that MAO inhibition does not entirely account for the antidepressant-like effects of selegiline. Administration of selegiline (10 mg/kg), but not rasagiline (1 mg/kg), to MPTP mice restored the impaired long-term potentiation induced by high-frequency stimulation in the medial prefrontal cortex (mPFC), and normalized the reduced phosphorylation of Ca 2+ /calmodulin-dependent protein kinase IIα, which is known to be involved in neuroplasticity, in the frontal cortex. In MPTP mice, the antiparkinsonian drug pramipexole (0.3 mg/kg), a DA D 2 and D 3 receptor agonist, that has been shown to be effective in treating depression in PD, ameliorated depression-like behavior and synaptic dysfunction in the mPFC. Taken together, the antidepressant-like effects of selegiline in MPTP mice are attributable to the restoration of impaired synaptic plasticity in the mPFC, suggesting its potential for treating depression in early PD.

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This study investigates the effect of blue light emitted by phosphor-converted white light-emitting diodes (LEDs) on people s eye fatigue. We conducted an experiment in which participants performed a visual task under lighting conditions using a white LED (B-LED) in which blue light excites phosphors and white LEDs (V-LEDs) in which violet light excites two types of phosphors. One of the two V-LEDs had a spectral power distribution mimicking those of the sun (S-LED). During the experiment, we measured participants subjective eye fatigue, number of eye blinks, accommodation power and critical flicker frequency. The results of the subjective evaluation suggested that participants eye fatigue under the B-LED lighting was worse than under the S-LED or V-LED lighting. The results of the eyeblink and accommodation measurements suggested that participants eye fatigue under the B-LED lighting was worse than under the S-LED lighting. In the range of the white LEDs employed in our experiment, we found that participants eye fatigue under lighting conditions with a blue-light-excited white LED could be worse than under a violetlight-excited white LED. The results of the objective response measurements suggested that the fatigue of eye muscles is the principal factor causing subjective eye fatigue.