Dataset Information

The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain.

ABSTRACT: In the healthy adult brain, neurogenesis normally occurs in the subventricular zone (SVZ) and hippocampal dentate gyrus (DG). Cerebral ischemia enhances neurogenesis in neurogenic and non-neurogenic regions of the ischemic brain of adult rodents. This study demonstrated that post-insult treatment with a histone deacetylase inhibitor, sodium butyrate (SB), stimulated the incorporation of bromo-2'-deoxyuridine (BrdU) in the SVZ, DG, striatum, and frontal cortex in the ischemic brain of rats subjected to permanent cerebral ischemia. SB treatment also increased the number of cells expressing polysialic acid-neural cell adhesion molecule, nestin, glial fibrillary acidic protein, phospho-cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) in various brain regions after cerebral ischemia. Furthermore, extensive co-localization of BrdU and polysialic acid-neural cell adhesion molecule was observed in multiple regions after ischemia, and SB treatment up-regulated protein levels of BDNF, phospho-CREB, and glial fibrillary acidic protein. Intraventricular injection of K252a, a tyrosine kinase B receptor antagonist, markedly reduced SB-induced cell proliferation detected by BrdU and Ki67 in the ipsilateral SVZ, DG, and other brain regions, blocked SB-induced nestin expression and CREB activation, and attenuated the long-lasting behavioral benefits of SB. Together, these results suggest that histone deacetylase inhibitor-induced cell proliferation, migration and differentiation require BDNF-tyrosine kinase B signaling and may contribute to long-term beneficial effects of SB after ischemic injury.

SUBMITTER: Kim HJ

PROVIDER: S-EPMC2726719 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain.

Kim Hyeon Ju HJ Leeds Peter P Chuang De-Maw DM

Journal of neurochemistry 20090615 4

In the healthy adult brain, neurogenesis normally occurs in the subventricular zone (SVZ) and hippocampal dentate gyrus (DG). Cerebral ischemia enhances neurogenesis in neurogenic and non-neurogenic regions of the ischemic brain of adult rodents. This study demonstrated that post-insult treatment with a histone deacetylase inhibitor, sodium butyrate (SB), stimulated the incorporation of bromo-2'-deoxyuridine (BrdU) in the SVZ, DG, striatum, and frontal cortex in the ischemic brain of rats subjec ...[more]

PMID: 19549282

Similar Datasets

Project description:Neonatal hypoxic-ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic-ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels was observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathological of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE. Targeted SCFA brain metabolomics is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4933' rel='noopener noreferrer' target='_blank'>MTBLS4933</a>.Untargeted fecal metabolomics is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4932' rel='noopener noreferrer' target='_blank'>MTBLS4932</a>.

Project description:The complication of type 2 diabetes (T2D) exacerbates brain infarction in acute ischemic stroke (AIS). Because butyrate-producing bacteria are decreased in T2D and butyrate has been reported to be associated with attenuated brain injury in AIS, we hypothesize that administering butyrate could ameliorate T2D-associated exacerbation of brain infarction in AIS. Therefore, we first validated that Chinese AIS patients with T2D comorbidity have significantly lower levels of fecal butyrate-producing bacteria and butyrate than AIS patients without T2D. Then, we performed a 4-week intervention in T2D mice receiving either sodium butyrate (SB) or sodium chloride (NaCl) and found that SB improved the diabetic phenotype, altered the gut microbiota, and ameliorated brain injury after stroke. Fecal samples were collected from T2D mice after SB or NaCl treatment and were transplanted into antibiotic-treated C57BL/6 mice. After 2 weeks of transplantation, the gut microbiota profile and butyrate level of recipient mice were tested, and then the recipient mice were subjected to ischemic stroke. Stroke mice that received gut microbiota from SB-treated mice had a smaller cerebral infarct volume than mice that received gut microbiota from NaCl-treated mice. This protection was also associated with improvements in gut barrier function, reduced serum levels of lipopolysaccharide (LPS), LPS binding protein (LBP), and proinflammatory cytokines, and improvements in the blood-brain barrier. IMPORTANCE Ischemic stroke is a major global health burden, and T2D is a well-known comorbidity that aggravates brain injury after ischemic stroke. However, the underlying mechanism by which T2D exacerbates stroke injury has not been completely elucidated. A large amount of evidence suggests that the gut microbiota composition affects stroke outcomes. Our results showed that the gut microbiota of T2D aggravated brain injury after ischemic stroke and could be modified by SB to afford neuroprotection against stroke injury. These findings suggest that supplementation with SB is a potential therapeutic strategy for T2D patients with ischemic stroke.

Project description:Neonatal hypoxic-ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic-ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels was observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathological of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE. Untargeted fecal metabolomics is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4932' rel='noopener noreferrer' target='_blank'>MTBLS4932</a>.Targeted SCFA brain metabolomics is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4933' rel='noopener noreferrer' target='_blank'>MTBLS4933</a>.

Project description:Here, we examined mouse brain trancriptional changes 1 hour after the 10th daily i.p. treament with one of the four following treaments: i) vehicle control (45% saline, 45% PEG-400 and 10% DMSO administered at 7.5mL/kg), ii) Cpd-60, 45mg/kg , administered at 7.5mL/kg or iii) SAHA, 25mg/kg, administered at 5mL/kg) or iv) CI-994, 10mg/kg, administered at 5mL/kg. Cpd-60 is a benzamide HDAC inhibitor with selectivity for class I HDAC subtypes HDAC1 and HDAC2; CI-994 is a benzamide inhibitor with selectivity for HDACs1,2 and 3; SAHA is a hydroxamic acid HDAC inhibitor with selectivity for class I HDAC subtypes 1,2, and 3 and the class II HDAC subtype HDAC 6. We examined transcript differences using the Illumnia WG-6 2.0 whole genome expression array and profiled 3 specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus) from each of 36 mice (n=6 mice / treatment group) . For application to array chips, we pooled two biological replicates from like treatment and brain region-groups such that 36 samples were applied in total: 4 treatment groups x 3 brain regions per treament group x 3 pools of two samples each for each treatment/brain region. Treatment groups: All adult male, C57BL/6 mice (n=6mice/treatment group) were sacrificed by rapid cervical dislocation and decapitation 1 hour after the tenth daily i.p. injection with one of the four following treaments: i) vehicle control (45% saline, 45% PEG-400 and 10% DMSO administered at 7.5mL/kg), ii) Cpd-60, 45mg/kg , administered at 7.5mL/kg or iii) SAHA, 25mg/kg, administered at 5mL/kg) or iv) CI-994, 10mg/kg, administered at 5mL/kg. Brains were removed, frozen immediately on dry ice and stored at -80°C until use. Frozen mouse brains (n = 6/ treatment group) were rapidly dissected at 4°C, isolating medial prefrontal cortex, nucleus accumbens and hippocampus. RNA was isolated using the Qiagen RNeasy Lipid Tissue mini kit, RNA concentration was determined using a NanoDrop spectrophotometer and quality was assessed using Agilent Bioanalyzer PICO chips, with the RNA Integrity Number (RIN) determined at 7.0-8.8 for all samples assayed, indicative of good RNA quality. For microarray experiments on Illumina MouseWG-6 BeadChips, RNA samples were pooled from two biological replicates such that the total number of samples was 36 (3 treatment groups x 3 brain regions x 3 RNA pools representing two mice per pool). All microarray analysis and gene set analysis (GSA) was performed using GeneSpring software (v.11.5.1) with raw signals adjusted using quantile normalization and baseline transformation with the median signal in all samples set to zero. Data were included in subsequent analyses if the normalized signal, thresholded at 0.8, was ‘present’ for 3 of 3 replicates for like treatment and tissue groups.

Dataset Information

The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain.

Publications

The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets