Neuroscience
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Prolonged neuronal depression after spreading depression (SD) is followed by a late cellular and synaptic hyperexcitability. Intra- and extracellular recordings of bioelectrical activities were performed in the rodent hippocampus to investigate the role of γ-aminobutyric acid (GABA)-mediated inhibition in the late hyperexcitable state of SD. The effect of KCl-induced negative DC potential shifts was investigated on extracellularly recorded paired-pulse depression (PPD) and bicuculline-induced afterdischarges as well as intracellularly recorded inhibitory post synaptic potentials (IPSPs) in the hippocampal CA1 area. ⋯ Application of low concentrations of bicuculline before the induction of SD enhanced the inhibitory effect of SD on IPSPs. Data indicate the contribution of GABA-mediated inhibition to SD-induced delayed hyperexcitability. Modulation of GABA function in the late hyperexcitability phase of SD may play a role in therapeutic management of SD-related neurological disorders.
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Circadian clocks drive daily rhythms in physiology and behavior which allow organisms to anticipate predictable daily changes in the environment. In most mammals, circadian rhythms result in nocturnal activity patterns although plasticity of the circadian system allows activity patterns to shift to different times of day. Such plasticity is seen when food access is restricted to a few hours during the resting (light) phase resulting in food anticipatory activity (FAA) in the hours preceding food availability. ⋯ Providing a chocolate meal at noon each day increased daytime activity, identifying food timing as a factor capable of altering the daily distribution of activity and rest. These results show that timing of food reward and energetic challenges are both independently sufficient to induce diurnality in nocturnal mammals. FAA observed following timed food restriction is likely the result of an additive effect of distinct regulatory pathways activated by energetic challenges and food reward.
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The blood-brain barrier (BBB) is formed by the endothelial cells with specialized tight junctions (TJs) lining the blood vessels and astroglial endfeet surrounding the blood vessels. Although BBB disruption during brain insults leads to vasogenic edema as one of the primary steps in the epileptogenic process, little is known about the molecular and physiological events concerning vasogenic edema formation. ⋯ Indeed, BQ788 (an ETB receptor antagonist) effectively attenuated SE-induced vasogenic edema by inhibiting eNOS-mediated MMP-9 activation and ZO-1 protein degradation in endothelial cells, although astroglial endfeet were detached from endothelial cells. Therefore, we suggest that SE-induced ETB receptor/eNOS-mediated MMP-9 activation may lead to impairments of endothelial cell function via TJ protein degradation, which are involved in vasogenic edema formation independent of perivascular astroglial functions.
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Icariin is derived most commonly from the traditional Chinese herb Epimedium brevicornum Maxim. Our previous studies have shown that icariin protects neurons from neurotoxic and ischemic conditions. This study aims to investigate the effect of icariin on the expression of amyloid precursor protein (APP) and the level of amyloid-β peptide (Aβ), as well as neurogenesis in the brain of Tg2576 mice, an animal model of Alzheimer's disease (AD). ⋯ Western blot analysis indicated the downregulation of APP expression after icariin treatment, and double staining showed an increased number of 5-bromo-2-deoxyuridine (BrdU)/Neuron-specific nuclear protein (NeuN) double-positive cells in the dentate gyrus region of the hippocampus in Tg2576+icariin mice compared with the Tg2576 mice. The current study demonstrated that icariin improved memory function, decreased the levels of Aβ and APP in the brain, and enhanced neurogenesis in the hippocampus of Tg2576 mice. Collectively, these results suggest the potential therapeutic value of icariin in AD.
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Positive allosteric modulators of GABAB receptors have great therapeutic potential for medications of anxiety, depression, etc. The effects of recently discovered modulator rac-BHFF on the key characteristics of GABAergic neurotransmission were investigated in cortical and hippocampal presynaptic nerve terminals of rats (synaptosomes). The ambient level of [(3)H]GABA that is a balance between release and uptake of the neurotransmitter increased significantly in the presence of rac-BHFF (at concentrations 10-30μM). ⋯ Rac-BHFF within the concentration range of 0.3-30μM did not enhance inhibiting effect of (±)-baclofen on depolarization-induced exocytotic release of [(3)H]GABA. Rac-BHFF (0.3-30μM) caused dose-dependent depolarization of the plasma membrane and dissipation of the proton gradient of synaptic vesicles in synaptosomes that was shown in the absence/presence of GABAB receptor antagonist saclofen using fluorescent dyes rhodamine 6G and acridine orange, respectively, and so, the above effects of rac-BHFF were not associated with the modulation of presynaptic GABAB receptors. Therefore, drug development strategy of positive allosteric modulation of GABAB receptors is to eliminate the above side effects of rac-BHFF in presynapse, and vice versa, these new properties of rac-BHFF may be exploited appropriately.