Impaired fear extinction in serotonin transporter knockout rats is associated with increased 5-hydroxymethylcytosine in the amygdala.
CNS Neurosci Ther
; 24(9): 810-819, 2018 09.
Article
en En
| MEDLINE
| ID: mdl-29427306
ABSTRACT
AIMS:
One potential risk factor for posttraumatic stress disorder (PTSD) involves the low activity (short; s) allelic variant of the serotonin transporter-linked polymorphic region (5-HTTLPR), possibly due to reduced prefrontal control over the amygdala. Evidence shows that DNA methylation/demethylation is crucial for fear extinction in these brain areas and is associated with neuronal activation marker c-Fos expression. We hypothesized that impaired fear extinction in serotonin transporter knockout (5-HTT-/- ) rats is related to changes in DNA (de) methylation and c-Fos expression in the prefrontal cortex (PFC) and/or amygdala.METHODS:
5-HTT-/- and 5-HTT+/+ rats were subjected to fear extinction. 2 hours after the extinction session, the overall levels of DNA methylation (5-mC), demethylation (5-hmC), and c-Fos in fear extinction and nonfear extinction rats were measured by immunohistochemistry.RESULTS:
5-HTT-/- rats displayed decreased fear extinction. This was associated with reduced c-Fos activity in the infralimbic PFC. In the central nucleus of the amygdala, c-Fos immunoreactivity was increased in the fear extinction group compared to the no-fear extinction group, regardless of genotype. 5-hmC levels were unaltered in the PFC, but reduced in the amygdala of nonextinction 5-HTT-/- rats compared to nonextinction wild-type rats, which caught up to wild-type levels during fear extinction. 5-mC levels were stable in central amygdala in both wild-type and 5-HTT-/- extinction rats. Finally, c-Fos and 5-mC levels were correlated with the prelimbic PFC, but not amygdala.CONCLUSIONS:
In the amygdala, DNA demethylation, independent from c-Fos activation, may contribute to individual differences in risk for PTSD, as conferred by the 5-HTTLPR s-allele.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
5-Metilcitosina
/
Proteínas de Transporte de Serotonina en la Membrana Plasmática
/
Extinción Psicológica
/
Miedo
/
Amígdala del Cerebelo
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
CNS Neurosci Ther
Asunto de la revista:
NEUROLOGIA
/
TERAPEUTICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Países Bajos