Dataset Information

Smolen2018 - Paradoxical LTP maintenance with inhibition of protein synthesis and the proteasome

ABSTRACT: This is a mathematical model describing the formation of long-term potentiation (LTP) at the Schaffer collateral of CA1 pyramidal cell synapse. The model consists of nine ordinary differential equations that denote synaptic states associated with different degrees of LTP, as well as the levels of regulatory proteins involved in the formation and maintenance of LTP.

SUBMITTER: Johannes Meyer

PROVIDER: BIOMD0000000853 | BioModels | 2019-11-12

REPOSITORIES: BioModels

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Publications

Paradoxical LTP maintenance with inhibition of protein synthesis and the proteasome suggests a novel protein synthesis requirement for early LTP reversal.

Smolen Paul P Baxter Douglas A DA Byrne John H JH

Journal of theoretical biology 20180821

The transition from early long-term potentiation (E-LTP) to late long-term potentiation (L-LTP) is a multistep process that involves both protein synthesis and degradation. The ways in which these two opposing processes interact to establish L-LTP are not well understood, however. For example, L-LTP is attenuated by inhibiting either protein synthesis or proteasome-dependent degradation prior to and during a tetanic stimulus (e.g., Huang et al., 1996; Karpova et al., 2006), but paradoxically, L- ...[more]

PMID: 30138630

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Project description:Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan; however, the mosaic of molecular changes responsible CR benefits remain unclear, particularly in brain regions susceptible to deterioration throughout aging. Thus, we examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimerâs disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses an age-dependent signature of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger- (5 months) and older-adult (15 months) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa proteins 1b and 5 (Hspa1b and Hspa5), protein disulfide isomerase family A members 4 and 6 (Pdia4 and Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR throughout adulthood, although the global CR-specific expression profiles at young and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within hippocampal CA1 throughout aging. Hippocampal CA1 region mRNA profiles of younger- (5 months) and older-adult (15 months) mice on calorie-restricted (CR) and normal (AD) diets were generated by deep sequencing using Illumina HiSeq 2500.

Dataset Information

Smolen2018 - Paradoxical LTP maintenance with inhibition of protein synthesis and the proteasome

Publications

Paradoxical LTP maintenance with inhibition of protein synthesis and the proteasome suggests a novel protein synthesis requirement for early LTP reversal.

Similar Datasets

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