Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387360319> ?p ?o ?g. }
- W4387360319 abstract "Abstract Temporal lobe epilepsy (TLE) is a type of focal epilepsy characterized by spontaneous recurrent seizures originating from the hippocampus. The epigenetic reprogramming hypothesis of epileptogenesis suggests that the development of TLE is associated with alterations in gene transcription changes resulting in a hyperexcitable network in TLE. DNA 5-methylcytosine (5-mC) is an epigenetic mechanism that has been associated with chronic epilepsy. However, the contribution of 5-hydroxymethylcytosine (5-hmC), a product of 5-mC demethylation by the Ten-Eleven Translocation (TET) family proteins in chronic TLE is poorly understood. 5-hmC is abundant in the brain and acts as a stable epigenetic mark altering gene expression through several mechanisms. Here, we found that the levels of bulk DNA 5-hmC but not 5-mC were significantly reduced in the hippocampus of human TLE patients and in the kainic acid (KA) TLE rat model. Using 5-hmC hMeDIP-sequencing, we characterized 5-hmC distribution across the genome and found bidirectional regulation of 5-hmC at intergenic regions within gene bodies. We found that hypohydroxymethylated 5-hmC intergenic regions were associated with several epilepsy-related genes, including Gal , SV2, and Kcnj11 and hyperdroxymethylation 5-hmC intergenic regions were associated with Gad65 , TLR4 , and Bdnf gene expression. Mechanistically, Tet1 knockdown in the hippocampus was sufficient to decrease 5-hmC levels and increase seizure susceptibility following KA administration. In contrast, Tet1 overexpression in the hippocampus resulted in increased 5-hmC levels associated with improved seizure resiliency in response to KA. These findings suggest an important role for 5-hmC as an epigenetic regulator of epilepsy that can be manipulated to influence seizure outcomes." @default.
- W4387360319 created "2023-10-06" @default.
- W4387360319 creator A5014922905 @default.
- W4387360319 creator A5016650953 @default.
- W4387360319 creator A5018125442 @default.
- W4387360319 creator A5019194272 @default.
- W4387360319 creator A5020755644 @default.
- W4387360319 creator A5034506936 @default.
- W4387360319 creator A5053650661 @default.
- W4387360319 creator A5068375574 @default.
- W4387360319 creator A5075346197 @default.
- W4387360319 date "2023-10-05" @default.
- W4387360319 modified "2023-10-12" @default.
- W4387360319 title "Alterations in DNA 5-hydroxymethylation Patterns in the Hippocampus of an Experimental Model of Refractory Epilepsy" @default.
- W4387360319 cites W1491724702 @default.
- W4387360319 cites W1519097303 @default.
- W4387360319 cites W1551911662 @default.
- W4387360319 cites W1964948396 @default.
- W4387360319 cites W1967297637 @default.
- W4387360319 cites W1981463058 @default.
- W4387360319 cites W1984152669 @default.
- W4387360319 cites W1984253712 @default.
- W4387360319 cites W1987436202 @default.
- W4387360319 cites W1987904402 @default.
- W4387360319 cites W1989457196 @default.
- W4387360319 cites W1990689143 @default.
- W4387360319 cites W1999380027 @default.
- W4387360319 cites W2001285906 @default.
- W4387360319 cites W2018338317 @default.
- W4387360319 cites W2022981588 @default.
- W4387360319 cites W2026221332 @default.
- W4387360319 cites W2026255880 @default.
- W4387360319 cites W2029826677 @default.
- W4387360319 cites W2031419550 @default.
- W4387360319 cites W2033242795 @default.
- W4387360319 cites W2038449573 @default.
- W4387360319 cites W2040971957 @default.
- W4387360319 cites W2041028481 @default.
- W4387360319 cites W2047246007 @default.
- W4387360319 cites W2056607606 @default.
- W4387360319 cites W2057068414 @default.
- W4387360319 cites W2059030268 @default.
- W4387360319 cites W2068632053 @default.
- W4387360319 cites W2070950696 @default.
- W4387360319 cites W2073902410 @default.
- W4387360319 cites W2083974405 @default.
- W4387360319 cites W2085556169 @default.
- W4387360319 cites W2087887826 @default.
- W4387360319 cites W2088285277 @default.
- W4387360319 cites W2091658754 @default.
- W4387360319 cites W2092559397 @default.
- W4387360319 cites W2092765329 @default.
- W4387360319 cites W2103353215 @default.
- W4387360319 cites W2103486606 @default.
- W4387360319 cites W2103946141 @default.
- W4387360319 cites W2108622432 @default.
- W4387360319 cites W2108664872 @default.
- W4387360319 cites W2112305736 @default.
- W4387360319 cites W2113486281 @default.
- W4387360319 cites W2121090755 @default.
- W4387360319 cites W2126298144 @default.
- W4387360319 cites W2137808356 @default.
- W4387360319 cites W2148521032 @default.
- W4387360319 cites W2152451432 @default.
- W4387360319 cites W2158804744 @default.
- W4387360319 cites W2164953929 @default.
- W4387360319 cites W2166408148 @default.
- W4387360319 cites W2170023126 @default.
- W4387360319 cites W2170551349 @default.
- W4387360319 cites W2175445854 @default.
- W4387360319 cites W2177651097 @default.
- W4387360319 cites W2180739129 @default.
- W4387360319 cites W2205162919 @default.
- W4387360319 cites W2239037979 @default.
- W4387360319 cites W2299160489 @default.
- W4387360319 cites W2317132940 @default.
- W4387360319 cites W2321178059 @default.
- W4387360319 cites W2341539131 @default.
- W4387360319 cites W2345396069 @default.
- W4387360319 cites W2404442615 @default.
- W4387360319 cites W2407650432 @default.
- W4387360319 cites W2466314544 @default.
- W4387360319 cites W2537093412 @default.
- W4387360319 cites W2542521476 @default.
- W4387360319 cites W2556254414 @default.
- W4387360319 cites W2556493236 @default.
- W4387360319 cites W2580748127 @default.
- W4387360319 cites W2583150707 @default.
- W4387360319 cites W2584204419 @default.
- W4387360319 cites W2589091265 @default.
- W4387360319 cites W2590004992 @default.
- W4387360319 cites W2591243891 @default.
- W4387360319 cites W2592437555 @default.
- W4387360319 cites W2610508849 @default.
- W4387360319 cites W2615442414 @default.
- W4387360319 cites W2737414718 @default.
- W4387360319 cites W2740619280 @default.
- W4387360319 cites W2766429477 @default.
- W4387360319 cites W2766967795 @default.
- W4387360319 cites W2775939341 @default.