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Fig. 5 | Clinical Epigenetics

Fig. 5

From: BET bromodomain inhibitors PFI-1 and JQ1 are identified in an epigenetic compound screen to enhance C9ORF72 gene expression and shown to ameliorate C9ORF72-associated pathological and behavioral abnormalities in a C9ALS/FTD model

Fig. 5

Treatment with JQ1 reverses spatial memory impairment in 6-month-old C9BAC mice. a Schematic representation of the object location memory (OLM) task, in which mice were subjected to habituation, followed by exposure to two similar objects (“Training”). Twenty-four h later (“Test”) the animals were evaluated by re-exposure for 10 min to the same testing area with one non-displaced object (ND) and one displaced object (D). b Quantification shows normalized exploration time in seconds of individual 6-month-old male C9BAC and Ntg mice, before and after JQ1 treatment (i.p. 0.5 mg/kg/day for 7 days), with non-displaced (ND) versus displaced (D) objects. c Graph shows normalized exploration time in seconds (s) of C9BAC mice before and after JQ1 treatment. d Discrimination index shows the time spent in exploring the displaced object (D) over the total time exploring both objects (N + D). An index of > 0.5 indicates that mice can positively discriminate between the D and ND object. The data shows that treatment of C9BAC mice with JQ1 for 7 days rescues their OLM impairment, reaching spatial memory levels comparable to Ntg mice. e Graph shows total exploration time and indicates that C9BAC and Ntg mice have the same exploration capacity and that JQ1 treatment does not alter this. Bars represent means ± SEM. Statistical analysis was performed by one-way ANOVA. *P < 0.05 and **P < 0.01 relative to untreated C9BAC

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