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1.
FIG 9

FIG 9. Structures of the antipsychotics used in the study. From: Epigenetic GABAergic Targets in Schizophrenia and Bipolar Disorder.

A. Guidotti, et al. Neuropharmacology. ;60(0):1007-1016.

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2.
FIG 2

FIG 2. Cytosine methylation in a CpG island-enriched promoter region of reelin comparing various methods. From: Epigenetic GABAergic Targets in Schizophrenia and Bipolar Disorder.

A. Guidotti, et al. Neuropharmacology. ;60(0):1007-1016.

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3.
FIG 3

FIG 3. Valproate (VPA) increases reelin and GAD67 mRNAs and reverses L-methionine (MET)-induced downregulation of these mRNAs. From: Epigenetic GABAergic Targets in Schizophrenia and Bipolar Disorder.

MET 5.2 mmol/kg; GLY (glycine) 5.2 mmol/kg; VPA 2.2 mmol/kg s.c. twice daily for 15 days.
*p< 0.05 vs VEH; **p< 0.05 vs MET.
.

A. Guidotti, et al. Neuropharmacology. ;60(0):1007-1016.

CitationFull text

4.
FIG 6

FIG 6. Proposed mechanism of activity-dependent CpG-rich promoter demethylation. From: Epigenetic GABAergic Targets in Schizophrenia and Bipolar Disorder.

A. Following depolarization GADD45 α, β protein levels increase and GADD45 α, β bind to a methylated promoter region proximal to an acetylated histone (green).
B. GADD45 recruits a deaminase (DA), which converts 5-methylcytosine to thymine leading to a T:G mismatch.
C. GADD45 recruits a DNA glycosylase (GLY), which removes thymine from the T:G mismatch. Thymine is later replaced with an unmethylated cytosine.

A. Guidotti, et al. Neuropharmacology. ;60(0):1007-1016.

CitationFull text

5.
FIG 5

FIG 5. Clozapine increases acetylated H3-lysine9 frontal cortex levels at the reelin promoter. From: Epigenetic GABAergic Targets in Schizophrenia and Bipolar Disorder.

Open bars denote mice that did not receive valproate. Closed bars denote mice that received valproate (70 mg/kg s.c. twice a day for three days)
*p< 0.05; **p< 0.01 when compared with the respective controls.
Controls are mice that did not receive valproate or clozapine.
For details see .

A. Guidotti, et al. Neuropharmacology. ;60(0):1007-1016.

CitationFull text

6.
FIG 7

FIG 7. Clozapine (CLZ) alone or in combination with valproate (VPA) increases GADD45 β mRNA expression in FC of mice. From: Epigenetic GABAergic Targets in Schizophrenia and Bipolar Disorder.

CLZ (5 mg/kg s.c./3 days/twice a day); VPA (70 mg/kg s.c./3 days/twice a day); VEH, vehicle. GADD45 β mRNA expression was measured two hours after the last drug injection.
*p< 0.05, **p< 0.01 vs VEH group. ANOVA followed by Bonferroni comparison; n=4–5 mice per group.

A. Guidotti, et al. Neuropharmacology. ;60(0):1007-1016.

CitationFull text

7.
FIG 1

FIG 1. Valproate (VPA) and clozapine (CLZ) accelerate the demethylation of methionine (MET*)-induced hypermethylation of reelin promoter. From: Epigenetic GABAergic Targets in Schizophrenia and Bipolar Disorder.

Met*: mice were pretreated with L-methionine (5.2 mmol/kg s.c. twice a day) for 7 days to hypermethylate the reelin promoter. At 7 days MET was withdrawn and mice received vehicle (VEH) or VPA or CLZ as indicated. Reelin promoter methylation was measured using MeDIP and quantitative PCR assays. Similar results were obtained for the GAD67 promoter.
(, ).

A. Guidotti, et al. Neuropharmacology. ;60(0):1007-1016.

CitationFull text

8.
FIG 4

FIG 4. Clozapine or olanzapine alone or in combination with valproate (VPA) but not haloperidol induce reelin promoter demethylation in the mouse frontal cortex. From: Epigenetic GABAergic Targets in Schizophrenia and Bipolar Disorder.

VPA (70 mg/kg) and antipsychotics were given s.c. twice a day for three days after MET withdrawal. Open circles denote MET-pretreated mice that did not receive VPA. Filled circles denote MET-pretreated mice that received VPA. Open squares denote mice never treated with MET.
*p< 0.05 when clozapine or olanzapine in absence of VPA were compared with the respective VEH-treated mice.
**p<0.01 when clozapine + VPA or olanzapine + VPA-treated mice were compared with VEH + VPA-treated mice.
# p< 0.05 when VEH + VPA-treated mice were compared with the respective VEH-treated mice.

A. Guidotti, et al. Neuropharmacology. ;60(0):1007-1016.

CitationFull text

9.
FIG 8

FIG 8. GADD45 β protein levels increase in FC neurons and coalesce in nuclei of mice treated with valproate. From: Epigenetic GABAergic Targets in Schizophrenia and Bipolar Disorder.

Mice were treated with either vehicle or 70 mg/kg s.c. valproate twice a day for three days. Samples were analyzed two hours after the last drug injection.
GADD45 β antibody (Santa Cruz) recognized a major band (~ 18 kDa) of immune-reactive material in western blot of FC extracts.I and II denote layers I and II of cortex.

A. Guidotti, et al. Neuropharmacology. ;60(0):1007-1016.

CitationFull text

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