Translational Psychiatry,
Год журнала:
2021,
Номер
11(1)
Опубликована: Сен. 1, 2021
Abstract
The
neuropeptide
oxytocin
(OXT)
and
its
receptor
(OXTR)
modulate
interpersonal
relationships,
particularly
mother–child
interactions.
DNA
methylation
(DNAm)
changes
of
the
OXTR
gene
were
observed
in
individuals
who
experienced
Childhood
Maltreatment
(CM).
A
modulatory
role
single
nucleotide
polymorphisms
(SNP)
within
association
with
CM
on
regulation
was
also
postulated.
Whether
these
CM-induced
epigenetic
alterations
are
biologically
inherited
by
offspring
remains
unknown.
We
thus
investigated
possible
intergenerational
effects
maternal
exposure
DNAm
expression,
additionally
accounting
for
influence
three
SNP:
rs53576
rs2254298
(
gene),
rs2740210
OXT
gene).
used
Trauma
Questionnaire
to
classify
mothers
into
(CM+)
or
without
(CM−).
Maternal
peripheral
immune
cells
isolated
from
venous
blood
N
=
117)
fetal
umbilical
cord
113)
after
parturition.
assessed
using
MassARRAY.
Taqman
assays
performed
genotyping
expression
analyses.
Among
mothers,
not
associated
mean
expression.
However,
four
CpG
sites
showed
different
levels
CM−
compared
CM+.
In
allelic
variations
interacted
load
methylation.
newborns’
positively
dyads,
but
CM+
dyads.
show
gene×environment
interactions
oxytocinergic
signaling
comparability
might
be
altered
infants
mothers.
Genes,
Год журнала:
2023,
Номер
14(8), С. 1639 - 1639
Опубликована: Авг. 17, 2023
Severe
or
chronic
stress
and
trauma
can
have
a
detrimental
impact
on
health.
Evidence
suggests
that
early-life
adversity
become
biologically
embedded
has
the
potential
to
influence
health
outcomes
decades
later.
Epigenetics
is
one
mechanism
been
implicated
in
these
long-lasting
effects.
Observational
studies
humans
indicate
effects
of
could
even
persist
across
generations,
although
whether
not
epigenetic
mechanisms
are
involved
remains
under
debate.
Here,
we
provide
an
overview
animals
demonstrate
DNA
methylation,
most
widely
studied
mechanisms,
summarize
findings
from
animal
models
demonstrating
involvement
epigenetics
transmission
generations.
We
then
describe
results
scoping
review
determine
extent
which
terms
intergenerational
transgenerational
used
human
investigating
via
mechanisms.
end
with
discussion
key
areas
for
future
research
advance
understanding
role
legacy
trauma.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(11), С. 5964 - 5964
Опубликована: Май 31, 2021
Stress
is
defined
as
a
state
of
threatened
or
perceived
homeostasis.
The
well-tuned
coordination
the
stress
response
system
necessary
for
an
organism
to
respond
external
internal
stressors
and
re-establish
Glucocorticoid
hormones
are
main
effectors
aberrant
glucocorticoid
signaling
has
been
associated
with
increased
risk
psychiatric
mood
disorders,
including
schizophrenia,
post-traumatic
disorder
depression.
Emerging
evidence
suggests
that
life-stress
experiences
can
alter
epigenetic
landscape
impact
function
genes
involved
in
regulation
response.
More
importantly,
changes
induced
by
persist
over
time,
leading
susceptibility
number
stress-related
disorders.
In
this
review,
we
discuss
role
glucocorticoids
response,
mechanism
through
which
stressful
become
biologically
embedded
alterations,
underline
potential
associations
between
development
Neuroscience & Biobehavioral Reviews,
Год журнала:
2021,
Номер
132, С. 1049 - 1066
Опубликована: Ноя. 3, 2021
Childhood
trauma
(CT)
can
have
persistent
effects
on
the
brain
and
is
one
of
major
risk
factors
for
neuropsychiatric
diseases
in
adulthood.
Recent
advances
field
epigenetics
suggest
that
epigenetic
such
as
DNA
methylation
histone
modifications,
well
regulatory
processes
involving
non-coding
RNA
are
associated
with
long-term
sequelae
CT.
This
narrative
review
summarizes
current
knowledge
basis
CT
describes
studies
animal
models
human
subjects
examining
how
epigenome
transcriptome
modified
by
brain.
It
discusses
psychological
pharmacological
interventions
counteract
changes
induced
need
to
establish
longitudinal
assessment
after
developing
more
effective
diagnostics
treatment
strategies
based
targets.
Cells,
Год журнала:
2023,
Номер
12(9), С. 1258 - 1258
Опубликована: Апрель 26, 2023
Stress
is
associated
with
various
epigenetic
changes.
Some
stress-induced
changes
are
highly
dynamic,
whereas
others
lasting
marks
on
the
epigenome.
In
our
study,
a
comprehensive
narrative
review
of
literature
was
performed
by
investigating
that
occur
acute
stress,
chronic
early
childhood
and
traumatic
stress
exposures,
along
examining
those
observed
in
post-mortem
brains
or
blood
samples
suicide
completers
attempters.
addition,
transgenerational
effects
these
reported.
For
all
types
studies
examined,
genes
Nr3c1,
OXTR,
SLC6A4,
BDNF
reproducibly
showed
changes,
some
modifications
to
be
passed
down
subsequent
generations
following
exposures.
The
aforementioned
known
involved
neuronal
development
hormonal
regulation
susceptibility
mental
health
disorders
including
depression,
anxiety,
personality
disorders,
PTSD
(post-traumatic
disorder).
Further
research
warranted
order
determine
scope
actionable
targets
individuals
suffering
from
long-lasting
stressful
experiences.
European Journal of Neuroscience,
Год журнала:
2021,
Номер
55(9-10), С. 2253 - 2296
Опубликована: Июнь 25, 2021
Childhood
trauma
(CT)
is
well
established
as
a
potent
risk
factor
for
the
development
of
mental
disorders.
However,
potential
adverse
early
experiences
to
exert
chronic
and
profound
effects
on
physical
health,
including
aberrant
metabolic
phenotypes,
has
only
been
more
recently
explored.
Among
these
consequences
syndrome
(MetS),
which
characterised
by
at
least
three
five
related
cardiometabolic
traits:
hypertension,
insulin
resistance/hyperglycaemia,
raised
triglycerides,
low
high-density
lipoprotein
central
obesity.
The
deleterious
CT
health
outcomes
may
be
partially
attributable
dysregulation
hypothalamic-pituitary-adrenal
(HPA)
axis,
coordinates
response
stress,
consequent
fostering
pro-inflammatory
environment.
Epigenetic
tags,
such
DNA
methylation,
are
sensitive
environmental
influences
provide
means
whereby
can
biologically
embedded
persist
into
adulthood
affect
well-being.
methylome
regulates
transcription
genes
involved
in
stress
response,
metabolism
inflammation.
This
narrative
review
examines
evidence
methylation
MetS
order
identify
shared
neuroendocrine
immune
correlates
that
mediate
increased
following
exposure.
Our
specifically
highlights
differential
FKBP5,
gene
encodes
FK506-binding
protein
51
pleiotropic
responding,
inflammation
energy
metabolism,
candidate
understand
molecular
aetiology
underlying
CT-associated
risk.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(10), С. 5157 - 5157
Опубликована: Май 13, 2021
Post-traumatic
stress
disorder
(PTSD)
is
a
neuropsychiatric
occurring
in
susceptible
individuals
following
traumatic
event.
Understanding
the
mechanisms
subserving
trauma
susceptibility/resilience
essential
to
develop
new
effective
treatments.
Increasing
evidence
suggests
that
non-coding
RNAs,
such
as
microRNAs
(miRNAs),
may
play
prominent
role
mediating
susceptibility/resilience.
In
this
study,
we
evaluated
transcriptional
expression
of
two
key
PTSD-related
genes
(FKBP5
and
BDNF)
relative
targeting
miRNAs
(miR-15a-5p,
miR-497a-5p,
miR-511-5p,
let-7d-5p)
brain
areas
resilient
mice
identified
through
our
recently
developed
mouse
model
PTSD
(arousal-based
individual
screening
(AIS)
model).
We
observed
lower
transcript
levels
miR-15a-5p,
miR-511a-5p
hippocampus
hypothalamus
compared
mice,
suggesting
these
could
discriminate
different
phenotypes
stress-exposed
mice.
These
miRNA
variations
contribute,
individually
or
synergically,
inversely
correlated
FKBP5
BDNF.
Conversely,
medial
prefrontal
cortex,
downregulation
let-7d-5p
was
both
not
accompanied
by
changes
their
mRNA
targets.
Furthermore,
stress-induced
behavioral
scores
(arousal
score,
avoidance-like
social
memory
score
PTSD-like
score),
linear
connection
between
miRNA-based
epigenetic
modulation
phenotypes.
Pathway
analysis
network
showed
statistically
significant
enrichment
molecular
processes
related
stress.
conclusion,
results
indicate
might
be
shaped
brain-area-dependent
FKBP5,
BDNF,
other
stress-related
genes.
Proceedings of the National Academy of Sciences,
Год журнала:
2020,
Номер
117(40), С. 24778 - 24784
Опубликована: Окт. 1, 2020
Significance
Mitochondrial
physiology
affected
by
childhood
maltreatment
(CM)
might
be
a
biological
link
for
the
intergenerational
transmission
of
CM-related
consequences.
As
mitochondria
are
intergenerationally
transmitted
from
mother
to
child,
alterations
in
mitochondrial
bioenergetics
influence
how
maternal
CM
affects
physical
and
mental
development
as
well
functioning
their
children.
Our
study
reports
data
on
peripheral
mononuclear
immune
cells
mother-newborn
dyads,
which
were
positively
correlated.
Higher
load
was
associated
with
higher
respiration
density
mothers,
but
not
newborns.
Thus,
we
found
no
evidence
an
effect
Frontiers in Immunology,
Год журнала:
2020,
Номер
11
Опубликована: Фев. 26, 2020
Maternal
stress
is
a
well-established
risk
factor
for
preterm
birth
and
has
been
associated
with
adverse
neonatal
outcomes
in
the
first
subsequent
generations,
including
increased
susceptibility
to
disease
lasting
immunological
changes.
However,
causal
link
between
prenatal
maternal
birth,
as
well
compromised
immunity,
yet
be
established.
To
fill
this
gap
knowledge,
we
used
murine
model
of
across
three
generations
high-dimensional
flow
cytometry
evaluate
adaptive
immunity.
We
report
that
recurrent
induced
second
filial
negatively
impacts
early
growth.
Strikingly,
systematic
reduction
T
cells
B
cells,
former
regulatory
CD4+
IL-4-
IL-17A-producing
generation.
Yet,
immunity
gained
resilience
against
by
third
also
show
rate
stress-induced
can
reduced
upon
cessation
stress,
though
growth
impairments
persisted.
These
findings
provide
evidence
causes
affects
effects
ameliorated
cessation.
