Journal of Neurochemistry,
Journal Year:
2023,
Volume and Issue:
166(2), P. 109 - 137
Published: March 15, 2023
Abstract
Since
it
was
first
generally
accepted
that
the
two
amino
acids
glutamate
and
GABA
act
as
principal
neurotransmitters,
several
landmark
discoveries
relating
to
this
function
have
been
uncovered.
Synaptic
homeostasis
of
these
transmitters
involves
cell
types
working
in
close
collaboration
is
facilitated
by
specialized
cellular
processes.
Notably,
are
extensively
recycled
between
neurons
astrocytes
a
process
known
glutamate/GABA‐glutamine
cycle,
which
essential
maintain
synaptic
transmission.
The
cycle
intimately
coupled
energy
metabolism
relies
on
metabolic
both
astrocytes.
Importantly,
display
unique
features
allowing
extensive
metabolite
release,
hereby
providing
support
for
neurons.
Furthermore,
undergo
complex
adaptations
response
injury
pathology,
may
greatly
affect
transmission
during
disease.
In
Milestone
Review
we
outline
major
relation
balancing
signaling,
including
uptake,
metabolism,
recycling.
We
provide
special
focus
how
astrocyte
contribute
sustain
neuronal
through
transfer.
Recent
advances
reviewed
context
brain
toxicity
neurodegeneration.
Finally,
consider
pathological
serve
potential
target
intervention.
Integrating
multitude
fine‐tuned
processes
supporting
neurotransmitter
recycling,
will
aid
next
generation
homeostasis.
image
Physiological Reviews,
Journal Year:
2017,
Volume and Issue:
98(1), P. 239 - 389
Published: Dec. 24, 2017
Astrocytes
are
neural
cells
of
ectodermal,
neuroepithelial
origin
that
provide
for
homeostasis
and
defense
the
central
nervous
system
(CNS).
highly
heterogeneous
in
morphological
appearance;
they
express
a
multitude
receptors,
channels,
membrane
transporters.
This
complement
underlies
their
remarkable
adaptive
plasticity
defines
functional
maintenance
CNS
development
aging.
tightly
integrated
into
networks
act
within
context
tissue;
astrocytes
control
at
all
levels
organization
from
molecular
to
whole
organ.
Physiological Reviews,
Journal Year:
2014,
Volume and Issue:
94(4), P. 1077 - 1098
Published: Oct. 1, 2014
Astrocytes
are
the
most
abundant
cells
in
central
nervous
system
(CNS)
that
provide
nutrients,
recycle
neurotransmitters,
as
well
fulfill
a
wide
range
of
other
homeostasis
maintaining
functions.
During
past
two
decades,
astrocytes
emerged
also
increasingly
important
regulators
neuronal
functions
including
generation
new
nerve
and
structural
functional
synapse
remodeling.
Reactive
gliosis
or
reactive
astrogliosis
is
term
coined
for
morphological
changes
seen
astroglial
cells/astrocytes
responding
to
CNS
injury
neurological
diseases.
Whereas
this
defensive
reaction
conceivably
aimed
at
handling
acute
stress,
limiting
tissue
damage,
restoring
homeostasis,
it
may
inhibit
adaptive
neural
plasticity
mechanisms
underlying
recovery
function.
Understanding
multifaceted
roles
healthy
diseased
will
undoubtedly
contribute
development
treatment
strategies
will,
context-dependent
manner
appropriate
time
points,
modulate
promote
brain
repair
reduce
impairment.
Molecular Neurodegeneration,
Journal Year:
2020,
Volume and Issue:
15(1)
Published: July 16, 2020
Abstract
Alzheimer’s
disease
(AD)
is
the
most
common
neurodegenerative
disorder
seen
in
age-dependent
dementia.
There
currently
no
effective
treatment
for
AD,
which
may
be
attributed
part
to
lack
of
a
clear
underlying
mechanism.
Studies
within
last
few
decades
provide
growing
evidence
central
role
amyloid
β
(Aβ)
and
tau,
as
well
glial
contributions
various
molecular
cellular
pathways
AD
pathogenesis.
Herein,
we
review
recent
progress
with
respect
Aβ-
tau-associated
mechanisms,
discuss
dysfunction
emphasis
on
neuronal
receptors
that
mediate
Aβ-induced
toxicity.
We
also
other
critical
factors
affect
pathogenesis,
including
genetics,
aging,
variables
related
environment,
lifestyle
habits,
describe
potential
apolipoprotein
E
(APOE),
viral
bacterial
infection,
sleep,
microbiota.
Although
have
gained
much
towards
understanding
aspects
this
devastating
disorder,
greater
commitment
research
mechanism,
diagnostics
will
needed
future
research.
Frontiers in Aging Neuroscience,
Journal Year:
2017,
Volume and Issue:
9
Published: July 6, 2017
Microglia,
the
immunocompetent
cells
of
central
nervous
system
(CNS),
act
as
neuropathology
sensors
and
are
neuroprotective
under
physiological
conditions.
Microglia
react
to
injury
degeneration
with
immune-phenotypic
morphological
changes,
proliferation,
migration,
inflammatory
cytokine
production.
An
uncontrolled
microglial
response
secondary
sustained
CNS
damage
can
put
neuronal
survival
at
risk
due
excessive
inflammation.
A
neuroinflammatory
is
considered
among
etiological
factors
major
aged-related
neurodegenerative
diseases
CNS,
key
players
in
these
lesions.
The
retina
an
extension
brain
therefore
occur
retina.
affected
several
diseases,
including
Alzheimer's
disease
(AD),
Parkinson's
(PD),
glaucoma.
AD
age-related
neurodegeneration
characterized
by
synaptic
loss
cerebral
cortex,
resulting
cognitive
deficit
dementia.
extracellular
deposits
beta-amyloid
(Aβ)
intraneuronal
accumulations
hyperphosphorylated
tau
protein
(pTau)
hallmarks
this
disease.
These
also
found
optic
nerve.
PD
a
locomotor
disorder
progressive
dopaminergic
neurons
substantia
nigra.
This
accompanied
Lewy
body
inclusion
composed
α-synuclein
(α-syn)
aggregates.
involves
retinal
cell
degeneration.
Glaucoma
multifactorial
nerve,
ganglion
loss.
In
pathology,
deposition
Aβ,
synuclein,
pTau
has
been
detected
share
common
pathogenic
mechanism,
neuroinflammation,
which
microglia
play
important
role.
Microglial
activation
reported
AD,
PD,
glaucoma
relation
aggregates
degenerated
neurons.
activated
release
pro-inflammatory
cytokines
aggravate
propagate
thereby
degenerating
impairing
well
function.
aim
present
review
describe
contribution
microglial-mediated
neuroinflammation
glaucomatous
neurodegeneration.
Journal of Neurochemistry,
Journal Year:
2016,
Volume and Issue:
139(6), P. 1019 - 1055
Published: July 1, 2016
The
adenosine
modulation
system
mostly
operates
through
inhibitory
A1
(A1
R)
and
facilitatory
A2A
receptors
(A2A
in
the
brain.
activity-dependent
release
of
acts
as
a
brake
excitatory
transmission
R,
which
are
enriched
glutamatergic
terminals.
Adenosine
sharpens
salience
information
encoding
neuronal
circuits:
high-frequency
stimulation
triggers
ATP
'activated'
synapse,
is
locally
converted
by
ecto-nucleotidases
into
to
selectively
activate
R;
R
switch
off
CB1
receptors,
bolster
glutamate
NMDA
assist
increasing
synaptic
plasticity
synapse;
parallel
engagement
astrocytic
syncytium
releases
further
inhibiting
neighboring
synapses,
thus
sharpening
encoded
plastic
change.
Brain
insults
trigger
large
outflow
ATP,
danger
signal.
hurdle
for
damage
initiation,
but
they
desensitize
upon
prolonged
activation.
However,
if
insult
near-threshold
and/or
short-duration,
preconditioning,
may
limit
spread
damage.
also
up-regulate
probably
adaptive
changes,
this
heightens
brain
since
blockade
affords
neuroprotection
models
epilepsy,
depression,
Alzheimer's,
or
Parkinson's
disease.
This
initially
involves
control
synaptotoxicity
whereas
microglia
might
signaling
mechanisms
largely
unknown
pleiotropic,
coupling
different
G
proteins
non-canonical
pathways
viability
neuroinflammation,
mitochondria
function,
cytoskeleton
dynamics.
Thus,
simultaneously
bolstering
preconditioning
preventing
excessive
function
afford
maximal
neuroprotection.
main
physiological
role
sharp
combined
action
synapse
undergoing
an
alteration
efficiency
with
increased
all
surrounding
synapses.
up-regulation
attempt
together
desensitization;
favors
synaptotocity
(increased
decreases
undergo
degeneration
(decreased
R).
Maximal
expected
result
from
article
part
mini
review
series:
"Synaptic
Function
Dysfunction
Diseases".
