Journal: Annals of Translational Medicine

Article Title: Astrocytic histone deacetylase 2 facilitates delayed depression and memory impairment after subarachnoid hemorrhage by negatively regulating glutamate transporter-1

doi: 10.21037/atm-20-4330

Figure Lengend Snippet: The expression of different HDACs in the hippocampal astrocytes of SAH mice after SAH and the effect of HDAC2 inhibition on GLT-1 expression. (A) Western blot detected the expression of different subtypes of class I and II HDACs in hippocampal astrocytes sorted from SAH mice. *, P<0.05, **, P<0.01, vs. the pre-1 week group. N=5 mice per group. (B) The co-localization of GLT-1, HDAC2 and GFAP was detected by immunofluorescence staining. Scale bar =100 µm, zoom in =50 µm. N=5 animals in each group. The protein (C) and mRNA (D) level of GLT-1 in the hippocampus of the mice. **, P<0.01, vs. the sham group; #, P<0.05, vs. the indicated groups. N=5 mice per group.

Article Snippet: The SAH mice were intraperitoneally administered with HDAC2 inhibitor (Santacruzamate A, Selleck, CAY10683, 2 mg/kg), GLT-1 inhibitor (MedChemExpress, WAY-213613, 1 mg/kg), and vehicle (10% Dimethyl sulfoxide (DMSO) + 90% (20% Sulfobutylether-β-Cyclodextrin (SBE-β-CD) in saline)) two weeks after surgery once every other day.

Techniques: Expressing, Inhibition, Western Blot, Immunofluorescence, Staining

Journal: Annals of Translational Medicine

Article Title: Astrocytic histone deacetylase 2 facilitates delayed depression and memory impairment after subarachnoid hemorrhage by negatively regulating glutamate transporter-1

doi: 10.21037/atm-20-4330

Figure Lengend Snippet: Effects of selective HDAC2 inhibitor and GLT-1 inhibitor on DCI in SAH mice. (A) The SAH mice were intraperitoneally administered with HDAC2 inhibitor (2 mg/kg) and GLT-1 inhibitor (WAY-213613, 1 mg/kg) two weeks after surgery once every other day. The expression of GLT-1, HDAC2, p-GluN2B and p-GluA1 in hippocampus was detected after SAH at 8 weeks. N=5 animals in each group. (B) Forced swimming test and (C) sugar water preference test were used to evaluate the depressive behavior of SAH mice treated with HDAC2 inhibitor (Santacruzamate A) and GLT-1 inhibitor (WAY-213613). **, P<0.01, vs. the sham group; #, P<0.05 and ##, P<0.01, vs. the indicated groups. (D) Morris water maze test was used to detect the escape latency for reflecting spatial learning memory, *, P<0.01, and **, P<0.01, vs. the indicated groups. (E) Reference memory was detected by recording the time in target quadrant of Morris water maze test. **, P<0.01, vs. the sham group; #, P<0.05, vs. the indicated groups. N=8 mice per group.

Article Snippet: The SAH mice were intraperitoneally administered with HDAC2 inhibitor (Santacruzamate A, Selleck, CAY10683, 2 mg/kg), GLT-1 inhibitor (MedChemExpress, WAY-213613, 1 mg/kg), and vehicle (10% Dimethyl sulfoxide (DMSO) + 90% (20% Sulfobutylether-β-Cyclodextrin (SBE-β-CD) in saline)) two weeks after surgery once every other day.

Techniques: Expressing

Journal: Annals of Translational Medicine

Article Title: Astrocytic histone deacetylase 2 facilitates delayed depression and memory impairment after subarachnoid hemorrhage by negatively regulating glutamate transporter-1

doi: 10.21037/atm-20-4330

Figure Lengend Snippet: Negative regulation of GLT-1 by astrocytes HDAC2 leads to dysfunction of glutamate reuptake in the synaptic cleft. In normal condition, the acetylation of histones in astrocytes facilitates the transcriptional regulation of GLT-1. Glutamate in the synaptic cleft is rapidly absorbed into astrocytes to maintain excitability of synapses. The increase of HDAC2 in astrocytes after SAH results in the deacetylation of histones and inhibits the transcription expression of GLT-1. The decrease of GLT-1 expression will lead to the impairment of glutamate reuptake in astrocytes and the long-term accumulation of glutamate in the synaptic space, resulting the dephosphorylation of ionized glutamate receptors GluN2B and GluA1 on the postsynaptic membrane. These eventually result in the long-term inhibition of synaptic excitability and DCI. DCI, delayed cognitive impairment.

Article Snippet: The SAH mice were intraperitoneally administered with HDAC2 inhibitor (Santacruzamate A, Selleck, CAY10683, 2 mg/kg), GLT-1 inhibitor (MedChemExpress, WAY-213613, 1 mg/kg), and vehicle (10% Dimethyl sulfoxide (DMSO) + 90% (20% Sulfobutylether-β-Cyclodextrin (SBE-β-CD) in saline)) two weeks after surgery once every other day.

Techniques: Expressing, De-Phosphorylation Assay, Membrane, Inhibition