Akademik Veri Yönetim Sistemi
Alcohol (Fayetteville, N.Y.), cilt.123, sa.2, ss.11-17, 2024 (SCI-Expanded, Scopus)
Early developmental exposure to alcohol has been implicated in adverse effects on the brain,
often associated with the onset of neurodevelopmental disorders. Moreover, maternal alcohol
consumption during pregnancy has been linked to the manifestation of mental health disorders,
such as depression and anxiety, in subsequent generations. These mood disturbances may be
attributed to alterations in protein expressions related to depression and anxiety within the
hippocampus. While the precise mechanisms remain elusive, it is likely that pre- and postnatal
exposure to alcohol induces changes in hippocampus, potentially through epigenetic
modifications. The FKBP5 gene, known to modulate the stress response, is particularly relevant
in this context. We postulate that alcohol-induced methylation of the FKBP5 gene disrupts HPA
axis function, thereby prompting individuals to anxiety-like and depressive-like behaviors. To
investigate this hypothesis, female C57BL/6 pups were subjected to early alcohol exposure via
intubation with ethanol mixed in artificial milk from Postnatal Day 3 to Day 20. The intubation
control pups were subjected to the same procedures without ethanol or milk, and a nonintubated control group included. Anxiety-like and depressive-like behaviors were assessed
using the open field test, plus maze test, forced swim test, and tail suspension test when the
pups reached 3 months of age. For epigenetic analysis of the FKBP5 gene, genomic DNA was
isolated from hippocampal tissues and subjected to bisulfite conversion to distinguish
methylated and unmethylated cytosines. Then, methylation-specific PCR was performed to
assess methylation levels. Pups exposed to early postnatal alcohol exhibited increased levels of
depression-like behavior and susceptibility to anxiety-like behavior during adolescence, as
verified by behavioral assessments. Methylation profiling revealed higher rates of methylation
within the stress-associated gene FKBP5 in both the early postnatal alcohol-exposed cohort
(13.82%) and the intubation control group (3.93%), in contrast to the control cohort devoid of
stress or alcohol exposure. These findings suggest a potential epigenetic mechanism underlying
the observed behavioral alterations, implicating FKBP5 methylation as a candidate mediator of
the increased vulnerability to mood disorders following early postnatal alcohol exposure