Dataset Information

Proteomic changes in aging rats treated with the cognitive enhancer CE-123

ABSTRACT: Aging rats with cognitive decline have been behaviourally evaluated and were divided into two groups, treated with CE-123, a dopamine transporter inhibitor, and vehicle. Memory-related brain areas were dissected and following sample preparation run on q-exactive from thermo fisher. Data handling and basic bioinformatics showed interesting differences pointing to several mechanisms.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Gert Lubec

LAB HEAD: Gert Lubec

PROVIDER: PXD022737 | Pride | 2022-02-16

REPOSITORIES: Pride

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Publications

Cognitive profiling and proteomic analysis of the modafinil analogue S-CE-123 in experienced aged rats.

Gyertyán István I Lubec Jana J Ernyey Alíz Judit AJ Gerner Christopher C Kassai Ferenc F Kalaba Predrag P Kozma Kata K Cobankovic Iva I Brenner Gábor G Wackerlig Judith J Franschitz Eva E Urban Ernst E Langer Thierry T Malikovic Jovana J Lubec Gert G

Scientific reports 20211214 1

The lack of novel cognitive enhancer drugs in the clinic highlights the prediction problems of animal assays. The objective of the current study was to test a putative cognitive enhancer in a rodent cognitive test system with improved translational validity and clinical predictivity. Cognitive profiling was complemented with post mortem proteomic analysis. Twenty-seven male Lister Hooded rats (26 months old) having learned several cognitive tasks were subchronically treated with S-CE-123 (CE-123 ...[more]

PMID: 34907284

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Project description:Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example the expression of an aversive behavior upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinctionare only beginning to emerge. Here we show that fear extinction initiates up-regulation of hippocampal insulin-growth factor 2 (Igf2) and down-regulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2-signaling during fear extinction. To this end we show that fear extinction-induced IGF2/IGFBP7-signaling promotes the survival of 17-19 day-old newborn hippocampal neurons. In conclusion, our data suggests that therapeutic strategies that enhance IGF2-signaling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory. We employed mice to investigate fear extinction in the hippocampus-dependent contextual fear conditioning paradigm. To this end, male C57BL/6J mice were exposed to the fear conditioning box (context) followed by an electric foot-shock which elicits the acquisition of conditioned contextual fear. For extinction training animals were repeatedly reexposed to the conditioned context on consecutive days (24h interval) without receiving the footshockagain (extinction trial, E). This procedure eventually results in the decline of the aversive freezing behavior. Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups. To gain a better understanding of the molecular processes underlying fear extinction we performed a genome-wide analysis of the hippocampal transcriptome during fear extinction. In the employed paradigm fear extinction is a gradual process. To capture the longitudinal course of fear extinction we decided to perform hippocampal microarray analysis at two time points: (1) After the first extinction trial (E1) when animals display high levels of aversive freezing behavior and (2) at the extinction trial on which the freezing behavior was significantly reduced when compared to E1. This extinction trial, in the case of this experiment E5, we termed “extinction trial low freezing” (ELF). Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups (3). For all three groups we hybridized 5 samples (biological replicates).

Dataset Information

Proteomic changes in aging rats treated with the cognitive enhancer CE-123

Publications

Cognitive profiling and proteomic analysis of the modafinil analogue S-CE-123 in experienced aged rats.

Similar Datasets

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