Brain,
Год журнала:
2016,
Номер
139(9), С. 2345 - 2371
Опубликована: Июнь 2, 2016
Cognitive
problems
are
one
of
the
main
causes
ongoing
disability
after
traumatic
brain
injury.
The
heterogeneity
injuries
sustained
and
variability
resulting
cognitive
deficits
makes
treating
these
difficult.
Identifying
underlying
pathology
allows
a
targeted
treatment
approach
aimed
at
enhancement.
For
example,
damage
to
neuromodulatory
neurotransmitter
systems
is
common
injury
an
important
cause
impairment.
Here,
we
discuss
evidence
implicating
disruption
catecholamines
(dopamine
noradrenaline)
review
efficacy
catecholaminergic
drugs
in
post-traumatic
impairments.
response
therapies
often
variable,
likely
consequence
heterogeneous
patterns
as
well
non-linear
relationship
between
catecholamine
levels
functions.
This
individual
means
that
measuring
structure
function
person's
allow
more
refined
therapy.
Advanced
structural
molecular
imaging
techniques
offer
potential
identify
provide
direct
measure
levels.
In
addition,
measures
functional
connectivity
can
be
used
functioning
'networks'
for
normal
functioning.
As
modulate
networks,
could
potentially
stratify
selection
monitor
sophisticated
manner.
impairment
following
common,
poorly
understood
difficult
treat.
Jenkins
et
al.
certain
neurotransmitters
persistent
impairments
propose
using
neuroimaging
guide
response.
Cells,
Год журнала:
2021,
Номер
10(4), С. 735 - 735
Опубликована: Март 26, 2021
Dopamine
(DA)
is
a
key
neurotransmitter
involved
in
multiple
physiological
functions
including
motor
control,
modulation
of
affective
and
emotional
states,
reward
mechanisms,
reinforcement
behavior,
selected
higher
cognitive
functions.
Dysfunction
dopaminergic
transmission
recognized
as
core
alteration
several
devastating
neurological
psychiatric
disorders,
Parkinson’s
disease
(PD),
schizophrenia,
bipolar
disorder,
attention
deficit
hyperactivity
disorder
(ADHD)
addiction.
Here
we
will
discuss
the
current
insights
on
role
DA
control
learning
mechanisms
its
involvement
synaptic
dynamics
through
different
pathways.
In
particular,
consider
neuromodulator
two
forms
plasticity,
known
long-term
potentiation
(LTP)
depression
(LTD)
cortical
subcortical
areas.
Finally,
delineate
how
effect
dendritic
spines
places
this
molecule
at
interface
between
systems.
Specifically,
be
focusing
PD,
vascular
dementia,
schizophrenia.
Science,
Год журнала:
2017,
Номер
358(6361), С. 381 - 386
Опубликована: Окт. 19, 2017
A
strategy
for
drug
discovery
Dopamine
receptors
are
G
protein-coupled
implicated
in
many
neurological
disorders.
Different
families
of
dopamine
involved
different
signaling
pathways,
so
specificity
is
a
key
goal
therapeutics.
Wang
et
al.
present
high-resolution
crystal
structures
the
DRD4
receptor
bound
to
antipsychotic
nemonapride.
The
high
resolution
facilitated
ligand
docking,
and
DRD4-selective
agonist
was
identified
by
computational
screening
large
library,
experimental
testing
compounds
with
best
docking
scores,
iterative
cycles
analogs
those
compounds.
had
affinity
no
measurable
DRD2
or
DRD3.
Science
,
this
issue
p.
381
Pharmacological Reviews,
Год журнала:
2022,
Номер
75(1), С. 62 - 158
Опубликована: Дек. 8, 2022
The
neurotransmitter
dopamine
is
a
key
factor
in
central
nervous
system
(CNS)
function,
regulating
many
processes
including
reward,
movement,
and
cognition.
Dopamine
also
regulates
critical
functions
peripheral
organs,
such
as
blood
pressure,
renal
activity,
intestinal
motility.
Beyond
these
functions,
growing
body
of
evidence
indicates
that
an
important
immunoregulatory
factor.
Most
types
immune
cells
express
receptors
other
dopaminergic
proteins,
take
up,
produce,
store,
and/or
release
dopamine,
suggesting
immunomodulation
for
function.
Targeting
pathways
could
be
promising
avenue
the
treatment
inflammation
disease,
but
despite
increasing
research
this
area,
data
on
specific
effects
disease
remain
inconsistent
poorly
understood.
Therefore,
review
integrates
current
knowledge
role
cell
function
inflammatory
signaling
across
systems.
We
discuss
understanding
regulation
CNS
tissues,
highlighting
diseases
Parkinson’s
several
neuropsychiatric
conditions,
neurologic
human
immunodeficiency
virus,
bowel
rheumatoid
arthritis,
others.
Careful
consideration
given
to
influence
experimental
design
results,
we
note
number
areas
need
further
research.
Overall,
our
immunology
at
cellular,
tissue,
level
prompts
development
therapeutics
strategies
targeted
toward
ameliorating
through
immunity.
Significance
Statement
Canonically,
recognized
involved
cognition,
reward.
However,
acts
modulator
periphery.
This
comprehensively
assesses
pathogenesis
cellular
tissue
level.
will
provide
broad
access
information
fields,
identify
investigation,
drive
therapeutic
strategies.
The
loss
of
nigrostriatal
dopamine
neurons
in
Parkinson's
disease
induces
a
reduction
the
number
dendritic
spines
on
medium
spiny
(MSNs)
striatum
expressing
D1
or
D2
receptor.
Consequences
MSNs
both
receptors
(D1/D2
MSNs)
are
currently
unknown.
We
looked
for
changes
induced
by
denervation
density,
regional
distribution
and
morphological
features
D1/D2
MSNs,
comparing
6-OHDA-lesioned
double
BAC
transgenic
mice
(Drd1a-tdTomato/Drd2-EGFP)
to
sham-lesioned
animals.
uniformly
distributed
throughout
dorsal
(1.9%
MSNs).
In
contrast,
they
heterogeneously
more
numerous
ventral
(14.6%
shell
7.3%
core).
Compared
endowed
with
smaller
cell
body
less
profusely
arborized
tree
spines.
spine
density
but
also
is
significantly
reduced
mice.
contrast
extent
arborization
appears
unaltered
Our
data
indicate
that
mouse
form
distinct
neuronal
population
affected
differently
deafferentation
characterizes
disease.
Neurotransmission
is
the
basis
of
neuronal
communication
and
critical
for
normal
brain
development,
behavior,
learning,
memory.
Exposure
to
drugs
chemicals
can
alter
neurotransmission,
often
through
unknown
pathways
mechanisms.
The
zebrafish
(Danio
rerio)
model
system
increasingly
being
used
study
chemical
neurotoxicity.
In
this
review,
major
neurotransmitter
systems,
including
glutamate,
GABA,
dopamine,
norepinephrine,
serotonin,
acetylcholine,
histamine,
glutamate
are
surveyed
synthesis,
transport,
metabolism,
action
examined.
Differences
between
human
neurochemical
highlighted.
We
also
review
techniques
evaluating
neurological
function,
measurement
levels,
assessment
gene
expression
transcriptomic
analysis,
recording
neurobehavior.
Finally
examples
toxicity
studies
alterations
in
systems
reviewed.
Journal of Neurochemistry,
Год журнала:
2016,
Номер
139(S1), С. 156 - 178
Опубликована: Фев. 11, 2016
Abstract
Dopamine‐releasing
neurons
within
the
Substantia
nigra
(SN
DA)
are
particularly
vulnerable
to
degeneration
compared
other
dopaminergic
neurons.
The
age‐dependent,
progressive
loss
of
these
is
a
pathological
hallmark
Parkinson's
disease
(PD),
as
resulting
striatal
dopamine
causes
its
major
movement‐related
symptoms.
SN
DA
release
from
their
axonal
terminals
dorsal
striatum,
and
also
cell
bodies
dendrites
midbrain
in
calcium‐
activity‐dependent
manner.
Their
intrinsically
generated
metabolically
challenging
activity
created
modulated
by
orchestrated
function
different
ion
channels
D2‐autoreceptors.
Here,
we
review
increasing
evidence
that
mechanisms
control
patterns
calcium
homeostasis
not
only
crucial
for
physiological
range
but
modulate
mitochondrial
lysosomal
activity,
metabolic
stress
levels,
vulnerability
PD.
Indeed,
impaired
homeostasis,
dysfunction,
represent
central
converging
trigger
factors
idiopathic
familial
We
summarize
double‐edged
roles
channels,
patterns,
related
feedback/feed‐forward
signaling
maintaining
modulating
function,
contributing
PD‐paradigms.
focus
on
emerging
maintained
neuronal
bandwidth,
modulation
PD‐triggers,
well
bidirectional
functions
voltage‐gated
L‐type
gated
ATP‐sensitive
potassium
(K‐ATP)
probable
interplay
health
image
propose
possess
several
feedback
feed‐forward
protect
adapt
activity‐pattern
calcium‐homeostasis
PD‐trigger
can
narrow
this
bandwidth.
view,
findings
documenting
both,
reduced
elevated
associated
calcium‐levels
degeneration.
This
article
part
special
issue
Parkinson
.