Abstract
We have previously shown that standardized extracts of Ginkgo biloba (EGb) modulate fear memory formation, which is associated with CREB-1 (mRNA and protein) upregulation in the dorsal hippocampal formation (dHF), in a dose-dependent manner. Here, we employed proteomic analysis to investigate EGb effects on different protein expression patterns in the dHF, which might be involved in the regulation of CREB activity and the synaptic plasticity required for long-term memory (LTM) formation. Adult male Wistar rats were randomly assigned to four groups (n = 6/group) and were submitted to conditioned lick suppression 30 min after vehicle (12% Tween 80) or EGb (0.25, 0.50, and 1.00 g⋅kg−1) administration (p.o). All rats underwent a retention test session 48 h after conditioning. Twenty-four hours after the test session, the rats were euthanized via decapitation, and dHF samples were removed for proteome analysis using two-dimensional polyacrylamide gel electrophoresis, followed by peptide mass fingerprinting. In agreement with our previous data, no differences in the suppression ratios (SRs) were identified among the groups during first trial of CS (conditioned stimulus) presentation (P > 0.05). Acute treatment with 0.25 g⋅kg−1 EGb significantly resulted in retention of original memory, without prevent acquisition of extinction within-session. In addition, our results showed, for the first time, that 32 proteins were affected in the dHF following treatment with 0.25, 0.50, and 1.00 g⋅kg−1 doses of EGb, which upregulated seven, 19, and five proteins, respectively. Additionally, EGb downregulated two proteins at each dose. These proteins are correlated with remodeling of the cytoskeleton; the stability, size, and shape of dendritic spines; myelin sheath formation; and composition proteins of structures found in the membrane of the somatodendritic and axonal compartments. Our findings suggested that EGb modulates conditioned suppression LTM through differential protein expression profiles, which may be a target for cognitive enhancers and for the prevention or treatment of neurocognitive impairments.
Highlights
The ability to extract meaning from sensory input, i.e., acquiring new knowledge about the world, and storing this information as past experiences for subsequent retrieval is part of the normal development of living beings and has been well studied in invertebrates animals (Carew and Sahley, 1986; Kandel et al, 2014)
The comparisons between trials showed a significant decrease in the mean suppression ratios (SRs) of the first trial compared with those of the three-trial blocks across all groups, except to group treated with 0.25 g·kg−1 dose during second three-trial block
Our data revealed elevated SR in the subgroups treated with extracts of Ginkgo biloba (EGb) at dose 0.25 g·kg−1 in relation to control group during second three-trial block, but in the subsequent trial, they had a reliable decrease in suppression and a reduction of fear, similar to all groups by the end of the session
Summary
The ability to extract meaning from sensory input, i.e., acquiring new knowledge about the world, and storing this information as past experiences for subsequent retrieval is part of the normal development of living beings and has been well studied in invertebrates animals (Carew and Sahley, 1986; Kandel et al, 2014) These events are largely coordinated and are crucial to memory formation, being characterized by specific cellular and/or molecular modifications that might last from seconds or minutes to hours. The maintenance of these signals, in parallel with other downstream activation targets, is necessary for long-lasting neuronal plasticity and cellular consolidation of memory, a protein synthesis-dependent stage of memory formation that may last for hours, weeks, or months
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