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Ginseng derivative ocotillol enhances neuronal activity through increased glutamate release: a possible mechanism underlying increased spontaneous locomotor activity of mice.

ABSTRACT: Ginsenosides are the main active ingredients in ginseng and have recently been reported to have beneficial effects on the CNS. Ocotillol is a derivate of pseudoginsenoside-F11, which is an ocotillol-type ginsenoside found in American ginseng. We examined the effects of ocotillol (a) on neuronal activity of projection neurons, mitral cells (MC), in a mouse olfactory bulb brain slice preparation using whole-cell patch-clamp recording, and (b) on animal behavior by measuring locomotor activity of mice in vivo. Ocotillol displayed an excitatory effect on spontaneous action potential firing and depolarized the membrane potential of MCs. The effect was concentration-dependent, with an EC(50) of 4 ?M. In the presence of blockers of ionotropic glutamatergic and GABAergic synaptic transmission (6-cyano-7-nitroquinoxaline-2,3-dione [CNQX], 10 ?M; D-AP5, 50 ?M; gabazine, 5 ?M), the excitatory effect of ocotillol on firing was abolished. Further experiments showed that the ocotillol-induced neuronal excitation persisted in the presence of GABA(A) receptor antagonist gabazine but was eliminated by applying AMPA/kainate receptor antagonist CNQX and N-methyl-d-aspartate (NMDA) receptor antagonist D-AP5, suggesting that ionotropic glutamate transmission was involved in mediating the effects of ocotillol. Bath application of ocotillol evoked an inward current as well as an increased frequency of spontaneous glutamatergic excitatory postsynaptic currents (EPSCs). Both the inward current and sEPSCs could be blocked by ionotropic glutamate receptor antagonists CNQX and D-AP5. These results indicate that the excitatory action of ocotillol on MCs was mediated by enhanced glutamate release. Behavioral experiments demonstrated that ocotillol increased locomotor activities of mice. Our results suggest that ocotillol-evoked neuronal excitability was mediated by increased release of glutamate, which may be responsible for the increased spontaneous locomotor activities in vivo.

SUBMITTER: Wang ZJ

PROVIDER: S-EPMC3193848 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Ginseng derivative ocotillol enhances neuronal activity through increased glutamate release: a possible mechanism underlying increased spontaneous locomotor activity of mice.

Wang Z-J ZJ Sun L L Peng W W Ma S S Zhu C C Fu F F Heinbockel T T

Neuroscience 20110812

Ginsenosides are the main active ingredients in ginseng and have recently been reported to have beneficial effects on the CNS. Ocotillol is a derivate of pseudoginsenoside-F11, which is an ocotillol-type ginsenoside found in American ginseng. We examined the effects of ocotillol (a) on neuronal activity of projection neurons, mitral cells (MC), in a mouse olfactory bulb brain slice preparation using whole-cell patch-clamp recording, and (b) on animal behavior by measuring locomotor activity of m ...[more]

PMID: 21864652

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Project description:Melatonin regulates diurnal changes in locomotor activity in vertebrates, but the molecular mechanism for this neurohormonal regulation of behavior is poorly understood. Here we show that 7alpha-hydroxypregnenolone, a previously undescribed avian neurosteroid, mediates melatonin action on diurnal locomotor rhythms in quail. In this study, we first identified 7alpha-hydroxypregnenolone and its stereoisomer 7beta-hydroxypregnenolone in quail brain. These neurosteroids have not been described previously in avian brain. We then demonstrated that 7alpha-hydroxypregnenolone acutely increased quail locomotor activity. To analyze the production of 7alpha-hydroxypregnenolone, cytochrome P450(7alpha), a steroidogenic enzyme of this neurosteroid, was also identified. Subsequently, we demonstrated diurnal changes in 7alpha-hydroxypregnenolone synthesis in quail. 7Alpha-Hydroxypregnenolone synthesis and locomotor activity in males were much higher than in females. This is the first demonstration in any vertebrate of a clear sex difference in neurosteroid synthesis. This sex difference in 7alpha-hydroxypregnenolone synthesis corresponded to the sex difference in locomotion. We show that only males exhibited marked diurnal changes in 7alpha-hydroxypregnenolone synthesis, and these changes occurred in parallel with changes in locomotor activity. Finally, we identified melatonin as a key component of the mechanism regulating 7alpha-hydroxypregnenolone synthesis. Increased synthesis of 7alpha-hydroxypregnenolone occurred in males in vivo after melatonin removal via pinealectomy and orbital enucleation (Px plus Ex). Conversely, decreased synthesis of this neurosteroid occurred after melatonin administration to Px plus Ex males. This study demonstrates that melatonin regulates synthesis of 7alpha-hydroxypregnenolone, a key factor for induction of locomotor activity, thus inducing diurnal locomotor changes in male birds. This is a previously undescribed role for melatonin.

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Ginseng derivative ocotillol enhances neuronal activity through increased glutamate release: a possible mechanism underlying increased spontaneous locomotor activity of mice.

Publications

Ginseng derivative ocotillol enhances neuronal activity through increased glutamate release: a possible mechanism underlying increased spontaneous locomotor activity of mice.

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