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Histone deacetylase inhibition facilitates massed pattern-induced synaptic plasticity and memory.

ABSTRACT: Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well understood. Here we show that increasing the level of acetylation enhances long-term potentiation induced by massed pattern of high frequency stimulation. Furthermore, enhancing acetylation level facilitates long-term memory by massed training. Thus, increasing acetylation level facilitates synaptic plasticity and memory by massed patterns.

SUBMITTER: Pandey K

PROVIDER: S-EPMC4579358 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Histone deacetylase inhibition facilitates massed pattern-induced synaptic plasticity and memory.

Pandey Kiran K Sharma Kaushik P KP Sharma Shiv K SK

Learning & memory (Cold Spring Harbor, N.Y.) 20150915 10

Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well understood. Here we show that increasing the level of acetylation enhances long-term potentiation induced by massed pattern of high frequency stimulation. F ...[more]

PMID: 26373830

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Project description:Short-chain fatty acids (SCFAs, especially butyric acid) have been demonstrated to play a promising role in the development of autism spectrum disorders (ASD). Recently, the hypothalamic-pituitary-adrenal (HPA) axis is also suggested to increase the risk of ASD. However, the mechanism underlying SCFAs and HPA axis in ASD development remains unknown. Here, we show that children with ASD exhibited lower SCFA concentrations and higher cortisol levels, which were recaptured in prenatal lipopolysaccharide (LPS)-exposed rat model of ASD. These offspring also showed decreased SCFA-producing bacteria and histone acetylation activity as well as impaired corticotropin-releasing hormone receptor 2 (CRHR2) expression. Sodium butyrate (NaB), which can act as histone deacetylases inhibitors, significantly increased histone acetylation at the CRHR2 promoter in vitro and normalized the corticosterone as well as CRHR2 expression level in vivo. Behavioral assays indicated ameliorative effects of NaB on anxiety and social deficit in LPS-exposed offspring. Our results imply that NaB treatment can improve ASD-like symptoms via epigenetic regulation of the HPA axis in offspring; thus, it may provide new insight into the SCFA treatment of neurodevelopmental disorders like ASD. IMPORTANCE Growing evidence suggests that microbiota can affect brain function and behavior through the "microbiome-gut-brain'' axis, but its mechanism remains poorly understood. Here, we show that both children with autism and LPS-exposed rat model of autism exhibited lower SCFA concentrations and overactivation of HPA axis. SCFA-producing bacteria, Lactobacillus, might be the key differential microbiota between the control and LPS-exposed offspring. Interestingly, NaB treatment contributed to the regulation of HPA axis (such as corticosterone as well as CRHR2) and improvement of anxiety and social deficit behaviors in LPS-exposed offspring. The potential underlying mechanism of the ameliorative effect of NaB may be mediated via increasing histone acetylation to the CRHR2 promoter. These results enhance our understanding of the relationship between the SCFAs and the HPA axis in the development of ASD. And gut microbiota-derived SCFAs may serve as a potential therapeutic agent to neurodevelopmental disorders like ASD.

Dataset Information

Histone deacetylase inhibition facilitates massed pattern-induced synaptic plasticity and memory.

Publications

Histone deacetylase inhibition facilitates massed pattern-induced synaptic plasticity and memory.

Similar Datasets

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