Proteome analysis indicates participation of the dorsal hippocampal formation in fear-motivated memory in a time-dependent manner.

Our previous behavioral and molecular data indicate a central role of the dorsal hippocampal formation (dHF) in recent conditioned lick suppression memory. The purpose of this study was to investigate the role of the dHF in recent and remote memory of conditioned lick suppression employing proteomic analysis. Two or 40 days after conditioning, the rats were subjected to a retention test and were then euthanized after 24 hr for dHF collection. We identified 1,165 proteins and quantified 265 proteins. Upregulation of five proteins and downregulation of 21 proteins were found on postconditioning Day 2. Additionally, four proteins were upregulated and 21 proteins were downregulated on postconditioning Day 40. Integrated pathway analysis of the proteomics data indicated changes in the myelin sheath, neuron generation and differentiation, regulation of neurogenesis and synaptic vesicle transport, axonal development, and the growth cone. Our findings provide further support for the role of the dHF in conditioned lick suppression memory and novel insights into the molecular changes that are correlated with recent and remote memory in the dHF, which may be a target for cognitive enhancers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Target Proteins in the Dorsal Hippocampal Formation Sustain the Memory-Enhancing and Neuroprotective Effects of Ginkgo biloba.

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.