Hippocampus-dependent cognitive enhancement induced by systemic gintonin administration

Abstract

BackgroundA number of neurological and neurodegenerative diseases share impaired cognition as a common symptom. Therefore, the development of clinically applicable therapies to enhance cognition has yielded significant interest. Previously, we have shown that activation of lysophosphatidic acid receptors (LPARs) via gintonin application potentiates synaptic transmission by the blockade of K+ channels in the mature hippocampus. However, whether gintonin may exert any beneficial impact directly on cognition at the neural circuitry level and the behavioral level has not been investigated.MethodsIn the current study, we took advantage of gintonin, a novel LPAR agonist, to investigate the effect of gintonin-mediated LPAR activation on cognitive performances. Hippocampus-dependent fear memory test, synaptic plasticity in the hippocampal brain slices, and quantitative analysis on synaptic plasticity-related proteins were used.ResultsDaily oral administration of gintonin for 1 wk significantly improved fear memory retention in the contextual fear-conditioning test in mice. We also found that oral administration of gintonin for 1 wk increased the expression of learning and memory-related proteins such as phosphorylated cyclic adenosine monophosphate-response element binding (CREB) protein and brain-derived neurotrophic factor (BDNF). In addition, prolonged gintonin administration enhanced long-term potentiation in the hippocampus.ConclusionOur observations suggest that the systemic gintonin administration could successfully improve contextual memory formation at the molecular and synaptic levels as well as the behavioral level. Therefore, oral administration of gintonin may serve as an effective noninvasive, nonsurgical method of enhancing cognitive functions.

Gintonin Attenuates D-Galactose-Induced Hippocampal Senescence by Improving Long-Term Hippocampal Potentiation, Neurogenesis, and Cognitive Functions

“…5a). Moreover, there was no difference in the discrimination ratio (F [3,34] = 0.775, p = 0.516; Fig. 5b).…”

“…5c). Furthermore, there was a significant difference in the discrimination ratio (F [3,34] = 5.238, p = 0.004; Fig. 5d), and post hoc comparisons revealed that the D-gal + gintonin (100 mg/kg, p.o.…”

“…Moreover, gintonin increases hippocampal synaptic transmission via LPA1 receptor [33]. In addition, in vitro gintonin treatment of hippocampal neural progenitor cells may have stimulated their proliferation by increasing the number of LPA1 receptors in hippocampal NPCs due to enhanced LPA1 receptor and brain-derived neurotrophic factor expression [23,34]. In vivo oral administration of gintonin increased hippocampal LPA1 receptor expression in adult transgenic AD mice [23].…”

A Review on the Potential Properties of Ginseng

“…Although when combined with other AD drugs it may improve the cognitive functions in AD patients (13). Gintonin which is relatively a new component of ginseng was found to improve memory formation in mice when administered systemically (14).…”

Plant Lysophosphatidic Acids: A Rich Source for Bioactive Lysophosphatidic Acids and Their Pharmacological Applications

“…22) Fourth, Kim et al observed that hippocampal long-term potentiation (LTP) increased in mice that were previously treated with gintonin for 7 d orally compared to saline-treated mice. 24) In addition, the hippocampi of mice that were previously treated for 7 d with gintonin showed increased expressions of learning and memory-related proteins such as phosphorylated cAMP-response element binding (pCREB) protein and brain-derived neurotrophic factor (BDNF). Finally, in a behavioral study, gintonin administration improved fear memory retention in the contextual fear-conditioning test in mice.…”