Echinacoside, an active constituent of Herba Cistanche, suppresses epileptiform activity in hippocampal CA3 pyramidal neurons

Echinacoside, an active compound in the herb Herba Cistanche, has been reported to inhibit glutamate release. In this study, we investigated the effects of echinacoside on spontaneous excitatory synaptic transmission changes induced by 4-aminopyridine (4-AP), by using the in vitro rat hippocampal slice technique and whole-cell patch clamp recordings from CA3 pyramidal neurons. Perfusion with echinacoside significantly suppressed the 4-AP-induced epileptiform activity in a concentration-dependent manner. Echinacoside reduced 4-AP-induced increase in frequency of spontaneous excitatory postsynaptic currents (sEPSCs) but it did not affect the amplitude of sEPSCs or glutamate-activated currents, implicating a presynaptic mechanism of action. Echinacoside also potently blocked sustained repetitive firing, which is a basic mechanism of antiepileptic drugs. These results suggest that echinacoside exerts an antiepileptic effect on hippocampal CA3 pyramidal neurons by simultaneously decreasing glutamate release and blocking abnormal firing synchronization. Accordingly, our study provides experimental evidence that echinacoside may represent an effective pharmacological agent for treating epilepsy.

Brain Plasticity and Neurorestoration by Environmental Enrichment

In the adult mammalian brain, neural-lineage cells are continuously generated in the subventricular zone (SVZ) and dentate gyrus of the hippocampus. These cells in vivo arising from the adult SVZ may be regulated by environmental enrichment (EE). EE is a method of raising animals in a huge cage containing novel objects, running wheels and social interaction with a complex combination of physical, cognitive, and social stimulations. EE can affect neural plasticity via overexpression of growth factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and synaptic activity-regulating genes. EE also have advanced effects on brain functions including the enhancement of motor and cognitive functions in normal and pathological states. Additionally, behavioral changes by EE are related with molecular changes including neurogenesis, gliogenesis, angiogenesis, axonal sprouting, and dendritic branching in the adult brain. In this review, we focus on brain plasticity and neurorestoration associated with molecular changes of neurotrophic growth factors such as BDNF, VEGF, IGF-1, FGF-2 and synaptic activity-regulating genes that occurs in interaction to EE.

Temporal Changes of Post Synaptic Signaling Molecules, Post Synaptic Density-95 and Neuronal Nitric Oxide Synthase, in the Inner Molecular Layer of the Mouse Dentate Gyrus during Voluntary Running / 대한해부학회지

Here, we investigated the temporal change of post synapse signaling molecules, post synaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS) using immunohistochemistry during voluntary running with upregulated neurogenesis. Rate of running was stabilized after two weeks of the six week trial. By using immunohistochemsitry for phosphorylated cAMP response element binding protein (pCREB) and polysialylatedneural cell adhesion molecules (PSA-NCAM), we observed that the differentiation in dentate granule cells of adult mouse hippocampus increased at 1 and 2 weeks of voluntary running. We found that, at 6 weeks of voluntary running, the differentiation in dentate granule cells of adult mouse hippocampus returned to sedentary control levels. On the other hand, PSD-95 and nNOS immunoreactivity decreased in the inner molecular layer in the dentate gyrus of hippocampus after 1 and 2 weeks of voluntary running. At 6 weeks of voluntary running, the density of the PSD-95 and nNOS in the inner molecular layer was returned to the sedentary control level. The reactivity of nicotinamide dinucleotide phosphate diaphorase (NADPH-diaphorase), the marker of nitric oxide synthase activity, confirmed the change of nNOS in the inner molecular layer during voluntary running. These results demonstrate that the differentiation and the synaptic activity of granule cells during voluntary running are changed reciprocally once the rate of running has stabilized. These granule cell changes during voluntary running suggest an adaptation response to the new environment.