BDNF as a Putative Target for Standardized Extract of Ginkgo biloba-Induced Persistence of Object Recognition Memory.

Beatriz G Muratori,Suzete M Cerutti,Janete M Cerutti,Bruno H N Nozima,Thaís B Mendes,Cláudia R Zamberlam

doi:10.3390/molecules26113326

Beatriz G Muratori, Suzete M Cerutti + Show 4 more

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https://doi.org/10.3390/molecules26113326

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Abstract

Despite considerable progress on the study of the effect of standardized extract of Gingko biloba (EGb) on memory processes, our understanding of its role in the persistence of long-term memory (LTM) and the molecular mechanism underlying its effect, particularly episodic-like memory, is limited. We here investigated the effects of EGb on the long-term retention of recognition memory and its persistence and BDNF expression levels in the dorsal hippocampal formation (DHF). Adult male Wistar rats (n = 10/group) were handled for 10 min/5 day. On day 6, the animals were treated with vehicle or 0.4 mg/kg diazepam (control groups) or with EGb (250, 500 or 100 mg/kg) 30 min before the training session (TR1), in which the animals were exposed to two sample objects. On day 7, all rats underwent a second training session (TR2) as described in the TR1 but without drug treatment. Object recognition memory (ORM) was evaluated on day 8 (retention test, T1) and day 9 (persistence test, T2). At the end of T1or T2, animals were decapitated, and DHF samples were frozen at −80 °C for analyses of the differential expression of BDNF by Western blotting. EGb-treated groups spent more time exploring the novel object in T2 and showed the highest recognition index (RI) values during the T1 and T2, which was associated with upregulation of BDNF expression in the DHF in a dose-and session-dependent manner. Our data reveal, for the first time, that EGb treatment before acquisition of ORM promotes persistence of LTM by BDNF differential expression.

Highlights

Flavonoids are bioactive molecules from plants or foods that, along with non-flavonoid compounds, are widely used to prevent or treat cognitive deficits.Extracts rich in flavonoids or flavonoid fractions have been associated with improvements in memory formation and stress-related memory processes [1,2,3]
We showed that extract of Ginkgo biloba (EGb) treatment before conditioning increased the levels of cAMP-dependent response element binding protein (CREB) expression in the dorsal hippocampal formation
Based on the findings from the present study, the persistence of memory is a process associated with mechanisms initiated during consolidation that persist over time

Summary

Introduction

Flavonoids (isoflavones, flavanones, anthocyanins, flavanols, flavones and flavonols) are bioactive molecules from plants or foods that, along with non-flavonoid compounds (phenolic acids and other phenols), are widely used to prevent or treat cognitive deficits.Extracts rich in flavonoids or flavonoid fractions have been associated with improvements in memory formation and stress-related memory processes [1,2,3]. A recent study showed that standardized extract of Ginkgo biloba (EGb), which is obtained from the dried leaves of the plant and is standardized to contain 24% to 27% ginkgo-flavonoglycosides and 6%. Ginkgo-terpenoid lactones [4], increases BDNF expression, which has a protective effect on neurons [5,6,7]. Standardized extract of Ginkgo biloba (EGb) has been used as a therapeutic alternative for the treatment of Alzheimer’s disease and multi-infarct dementias and has significant positive effects on cognitive function in patients with Alzheimer’s disease [8,9]. GTTLs increase BDNF expression in the hippocampus, which protects hippocampal neurons against epilepsy and improves spatial memory, as evaluated by the Morris Water Maze (MWM) test [5,10]

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