6 days ago · Additionally, to validate the causal role of increased HDAC1–dependent histone deacetylation in stress–induced Cldn5 loss, the HDAC1 inhibitor pyroxamide or vehicle was also directly infused into the bilateral hippocampus through an implanted cannula for 14 consecutive days following the 6–week CUMS procedure (Fig. S4A).

Feb 11, 2020 · We identified proinflammatory TNFα/NFκB signaling and hdac1 as mediators of stress susceptibility. Pharmacological inhibition of stress-induced increase in hdac1 activity rescued cldn5 expression in the NAc and promoted resilience.

HDAC1 inhibition with MS-275 restores social interaction and Cldn5 expression in depressed mice demonstrating that increased HDAC1 contributes to the depressive phenotype through regulation of blood brain barrier permeability.

The CLDN5 gene encodes claudin-5 (CLDN-5) that is expressed in endothelial cells and forms tight junctions which limit the passive diffusions of ions and solutes. The blood–brain barrier (BBB), composed of brain microvascular endothelial cells and ...

Dec 13, 2024 · To analyze the HDAC2 function, we utilized siRNAs to knockdown (KD) HDAC1, HDAC2, or HDAC3 in adult ECs. KD of HDAC2 significantly upregulated the repressed Cldn1 , Mfsd2a , and Zic3 genes and reduced Cldn5 expression ( Figure 2C , Figure 2—figure supplement 1B ).

Jun 6, 2023 · To analyze the HDAC2 function, we utilized siRNAs to downregulate HDAC1, HDAC2, or HDAC3 in adult ECs. Knockdown (KD) of HDAC2 significantly upregulated the repressed CLDN1 , MFSD2A , and ZIC3 genes and reduced CLDN5 expression (Fig-2C).

HDAC1 functions as a histone decrotonylase whose activity is modulated by inositol phosphates. To investigate the putative decrotonylase activity of class-I HDACs we synthesized analogous histone H3 tail peptides containing H3K18ac and H3K18cr modifications (Supplementary Fig. 1A).

(C) CLDN5 protein expression is reduced in postmortem NAc samples of depressed subjects when compared to healthy controls. (Scale bar, 100 μm.)

HDAC1 increased in the NAc of MDD patients and correlated with Cldn5 expression. HDAC1 expression increased in the endothelial cells of the NAc in stress-susceptible mice compared to resilient mice. HDAC1 expression in the NAc correlated with the degree of social interactions.

Dec 10, 2008 · Inhibition of HDAC1 activity by p25/Cdk5 was identified as an underlying mechanism for these events, and HDAC1 gain-of-function provided potent protection against DNA damage and neurotoxicity in cultured neurons and an in vivo model for ischemia.