Neuromodulatory property of standardized extract Ginkgo biloba L. (EGb 761) on memory: Behavioral and molecular evidence

Abstract Although it has been suggested that the standardized Ginkgo biloba leaf extract (Egb 761) may have a beneficial effect on memory, the cellular and molecular changes that underlie this process are not yet well defined. The present study evaluated the effects of acute (one dose) or subacute t...

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Published in:	Brain research Vol. 1269; pp. 68 - 89
Main Authors:	Oliveira, Daniela R, Sanada, Priscila F, Saragossa, Filho A.C, Innocenti, L.R, Oler, Gisele, Cerutti, Janete M, Cerutti, Suzete M
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 07-05-2009 Elsevier
Subjects:	Amygdala - drug effects Amygdala - physiology Animals Behavior, Animal - drug effects Behavioral psychophysiology Biological and medical sciences Brain - drug effects Brain - physiology Conditioning, Psychological - drug effects CREB-1 Cyclic AMP Response Element-Binding Protein - genetics Fear Fear conditioning Fundamental and applied biological sciences. Psychology GAP-43 GAP-43 Protein - genetics Gene Expression - drug effects GFAP Ginkgo biloba Glial Fibrillary Acidic Protein - genetics Hippocampus - drug effects Hippocampus - physiology Learning and memory Male Memory - drug effects Miscellaneous Neurology Plant Extracts - pharmacology Prefrontal Cortex - drug effects Prefrontal Cortex - physiology Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Rats Rats, Wistar Ginkgo biloba Learning and memory CREB-1 GAP-43 Fear conditioning GFAP Affect affectivity Rat Memory Learning Acquisition process Gymnospermae Behavior Conditioning Transcription factor CREB Growth associated protein 43 Glial fibrillary acidic protein Rodentia Emotion emotionality Fear Vertebrata Mammalia Animal Ginkgoales Spermatophyta
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Summary:	Abstract Although it has been suggested that the standardized Ginkgo biloba leaf extract (Egb 761) may have a beneficial effect on memory, the cellular and molecular changes that underlie this process are not yet well defined. The present study evaluated the effects of acute (one dose) or subacute treatments (one daily dose/seven days) with EGb 761 (0.5 g kg − 1 and 1.0 g kg − 1 ) on rats submitted to a conditioned emotional response (CER) in comparison with positive (4 mg kg − 1 Diazepam) and negative (12%Tween 80) control groups. To this end, eighty ( n = 10/group) adult, male, Wistar rats (± 250–300 g) were used in an off-baseline CER procedure. We here observed that the rats submitted to an acute and subacute EGb 761 treatments had acquisition of fear conditioning. Additionally, we investigate if the expression of genes previously associated with classical conditioning (CREB-1 and GAP-43) and new candidate genes (GFAP) are modulated following EGb 761 acute treatment. CREB-1, GAP-43 and GFAP mRNA and protein expressions were evaluated using both quantitative PCR (qPCR) and immunohistochemical analysis, respectively. We here show, for the first time, that EGb 761 modulated GAP-43, CREB-1 and GFAP expression in the prefrontal cortex, amygdala and hippocampus. We observed an underexpression of GAP-43 in all structures evaluated and over-expression of GFAP in the amygdala and hippocampus following acute G. biloba treatment when compared to control group (Tween; p < 0.01). GAP-43 expression was decreased in prefrontal cortex and hippocampus in the subacute treatment with EGb 761. Subacute treatment with EGb 761 lead to a decreased CREB-1 in mPFC ( p < 0.001) and increased in the hippocampus to 1.0 g kg − 1 G. biloba group ( p < 0.001). The results obtained from immunohistochemical analysis support our aforementioned findings and revealed that the changes in expression occurred within specific regions in the areas evaluated. All together, our findings not only provide new evidence for a role of EGb 761 on memory but also identify molecular changes that underlie the fear memory consolidation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-8993 1872-6240
DOI:	10.1016/j.brainres.2008.11.105