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Transcript of Eberhard Fuchs (Auth.), J. a. Costa e Silva, J. P. Macher, J. P. Olié (Eds.)-Neuroplasticity_ New...
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NEUROPLASTICITYNew Biochemical Mechanisms
Editors-in-chief
With contributions from
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CONTENTS
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iv
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CONTRIBUTOR BIOGRAPHIES
Jorge Alberto Costa e Silva
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Jean-Paul Macher
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v
Jean-Pierre Olié
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l’Encephale and member of the
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Eberhard Fuchs
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v
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vi
vi
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Lawrence Reagan
Jim Fadel
and Leah Reznikov
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vii
vii
Bruce McEwen
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The Hostage Brain
The End
of Stress as We Know It
Thérèse Jay
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viii
viii
The European Journal of Psychiatry and Frontiers in Neuroscience
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Philip Gorwood
Psychopharmacogenetics
European Psychiatry
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FOREWORD
Neuroplasticity
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second edition of Neuroplasticity — New Biochemical Mechanisms
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Neuroplasticity
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NEUROPLASTICITY – A NEW APPROACH TO THE PATHOPHYSIOLOGY OF DEPRESSION
Eberhard Fuchs
I Introduction
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II From neurotransmitter deficits to neuroplasticity –
the evolution of a concept
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Figure 1.
Debranching is prevented by
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Figure 2.
A
B
C
Control Stress Control Stress
Control Stress
A B
C
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III Depression and reduced hippocampal volume
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to chronic stress have been used to understand the cellular mechanisms
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IV Structural plasticity beyond the hippocampus
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Figure 3.
Stress, depression Antidepressant treatment
� �� �� ��� �� �
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neurochemical mechanisms could mediate the dendritic alterations seen
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Figure 4.
Prefrontal cortex
���
Hippocampus
����
Amygdala
�
metabolism
��
V Structural plasticity of glutamatergic axons
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VI The impact of glia
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Figure 5.
Steroid hormones
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VII Conclusions
References
1
2
3
4
5
6
7
8
9
10
11
12
13
14
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GLUTAMATE-MEDIATED NEUROPLASTICITY DEFICITS IN MOOD DISORDERS
Leah R. Reznikov, Jim R. Fadel
and Lawrence P. Reagan
I Introduction
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II The glutamatergic system
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N D
III Glutamatergic projections and anatomical substrates
of mood-related disorders
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IV Glutamatergic alterations in psychiatric illness: clinical evidence
Depressive illness
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Anxiety disorders
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Structure
Functions
Glutamate neuropharmacology
Neuroplasticity deficits in depressive illness
Table 1.
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V Understanding glutamate’s involvement in neuroplasticity:
functional implications in relation to psychiatric illness
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Figure 1.
-
Prefrontal Cortex
Hippocampus
Amygdala
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Long-term potentiation
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Morphological plasticity
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Treatment implications
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Figure 2.
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Imp
airm
en
ts in n
eu
rop
lastic
ity
Re
sto
rati
on
of
ne
uro
pla
stic
ity
Stress Tianeptine
ehavior
*
*
Hippocampus Amygdala
Tianeptine
Saline
Glu
tam
ate
lev
els
, % c
ha
ng
e f
rom
ba
seli
ne
Glutamate neurochemistry Glutamate pharmacology
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VI Conclusions
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References
1
2 -
3
4
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8
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15
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20
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REGULATION OF CELLULAR PLASTICITY IN MOOD DISORDERS: THE ROLE OF THE AMPA RECEPTOR
Per Svenningsson and Bruce S. McEwen
I Introduction
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II Neuroplasticity, glutamate, and glutamate receptors
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III Glutamate receptors
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N D
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IV NMDA receptors and their interaction with AMPA receptors
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V AMPA receptors
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VI Effects of stress on glutamate and glutamate receptors
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VII AMPA receptor phosphorylation and tianeptine
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VIII Relationships between AMPA receptor phosphorylation
and antidepressant effect
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Figure 1.
Cortex Hippocampus
CA3
Ph
osp
ho
ryla
ted
Se
r 8
31
-Glu
R1
(%
of
sali
ne
lev
el)
Acute
Tianeptine-treated animals
Saline-treated animals
Hippocampus
CA1
Cortex Hippocampus
CA3
Ph
osp
ho
ryla
ted
Se
r84
5-G
luR
1 (
% o
f sa
lin
e le
ve
l)Hippocampus
CA1
Cortex Hippocampus
CA3
Ph
osp
ho
ryla
ted
Se
r83
1-G
lur1
(%
of
sali
ne
lev
el)
Chronic
Tianeptine-treated animals
Saline-treated animals
Hippocampus
CA1
Cortex Hippocampus
CA3
Ph
osp
ho
ryla
ted
Se
r84
5-G
luR
1 (
% o
f sa
lin
e le
ve
l)
Hippocampus
CA1
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Figure 2. -
Saline Tianeptine
La
ten
cy
to
en
ter
ce
nte
r (s
ec
s)Open-field tests of exploration and locomotion
GluR1-phosphomutant mice
Wild-type mice
Saline TianeptineT
ota
l sq
ua
res
cro
sse
d
Saline Tianeptine
Lo
co
mo
tio
n (
be
am
bre
ak
s)
Saline Tianeptine
Imm
ob
ilit
y (
sec
s)
Tail-suspension test
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IX Conclusions
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References
1
2
3
4
5
6
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7
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8
9
10
11 -
12
13
14
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16
17
18
19
20
21
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CELLULAR PLASTICITY AND THE PATHOPHYSIOLOGY OF DEPRESSION
Thérèse M. Jay
I Introduction
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II Depression-induced changes in brain morphology and function
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III Effects of stress and depression on the hippocampus
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Animal models
Prefrontal cortex
Hippocampus
Amygdala
Patients with chronic depression
Prefrontal cortex
Hippocampus
Amygdala
volume retained
Orbitofrontal cortex
Neuromorphological changes in animal models of depression and
in depressed patients
Table 1.
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-
IV Beyond the hippocampus: the prefrontal cortex
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-
V Animal models of depression
Figure 1.
Ch
an
ge
in P
SP
am
pli
tud
e (
% b
ase
lin
e)
Stress + NaCl + LTP
LTP + NaCl
Stress + tianeptine + LTP
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-
-
VI Effects of stress on glutamatergic neurotransmission
in the hippocampus
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VII Structural changes
-
-
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VIII Modulation of stress-induced changes in the glutamate system
Effects of tianeptine on preventing stress-induced
impairment in LTP
-
-
Effects of tianeptine on inhibiting glutamate-dependent
stress-induced changes in hippocampal morphology
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-
Effects of tianeptine on inhibiting stress-induced changes in
glutamatergic neurotransmission
IX Clinical implications
Figure 2.
Saline-treated rats
Tianeptine-treated rats
Glu
tam
ate
lev
el (
% o
f b
ase
lin
e)
Sample number
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-
Figure 3.
Non-stressed
control
Glu
tam
ate
tra
nsp
ort
er
ex
pre
ssio
n
(% o
f c
on
tro
l)
Stressed animals
treated with saline
Stressed animals treated
with tianeptine
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-
X Conclusions
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Figure 4.
Day 7
Pa
tie
nts
de
scri
be
d a
s e
xtr
em
ely
or
sev
ere
ly il
l (%
) Fluoxetine
Tianeptine
Day 14P
ati
en
ts d
esc
rib
ed
as
no
t il
l at
all
or
bo
rde
rlin
e (
%)
Figure 5.
Day 7
Pa
tie
nts
sh
ow
ing
imp
rov
em
en
t in
co
nce
ntr
ati
on
dif
ficu
ltie
s (%
)
Fluoxetine
Tianeptine
Day 14
Pa
tie
nts
sh
ow
ing
imp
rov
em
en
ts in
inn
er
ten
sio
n (
%)
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References
1
2 -
3
4
5
6
-
7
8
9
10 -
11
12
13
14
15 -
16
17
-
18
19
20
21
22 -
23
24 -
25
26
27
28
29
30
31
32 -
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33 -
34
35
36
-
37
38
-
39
40
41
42
43 -
44
45
-
46 -
47
-
48
49
50
51
52
53
54
55
56
57
58 -
-
59 -
60
61
62 -
63
64
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65
66 -
67
68
69
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Philip Gorwood
I Introduction
-
II Relevency of stress in the model of depression regarding the role of europlasticity
-
CLINICAL CONSEQUENCES OF THE ROLE OF GLUTAMATE AND NEUROPLASTICITY IN DEPRESSIVE DISORDER
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III The place of neuroplasticity in the delay before treatment
efficacy can be observed
-
-
-
-
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N D
-
-
-
IV The role of neuroplasticity and glutamate in
non-pharmacological treatments
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-
-
-
V Are depressive episodes neurotoxic?
-
-
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Figure 1. A B C
C
B
stressful life events before
Le
ft h
ipp
oca
mp
al v
olu
me
(m
m3)
Nu
mb
er
de
tec
ted
str
ess
ful l
ife
ev
en
tsN
um
be
r o
f co
rre
ct
de
lay
ed
re
call
ev
en
ts
Depressive episodes
Depressive episodes
Depressive episodes
A
to the lifetime incidence of
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-
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-
VI Conclusions
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-
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References
1
2
-
3
4 -
5
-
6 -
7
-
8 -
9
10 -
11 -
12
-
13
-
14
-
15
an N D
16
17
-
18
-
19 -
20
21 -
22
23
24
25
26
-
27
-
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28
29
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30 -
31
32 -
33
34
35
36
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37 -
38
39
40
41
42
43
44
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Index
italics
acute stress see stress
34
4
18
22 52
-
4
50
see
cell loss see
chronic stress see stress
18
52
see also
see
-
6
see also
disorders
-
-
6
6
see
50
18
22 52
22
22
22
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22
6
see also
see also corticosteroids
52
see
45
see
see also
see
63
see N D
36
see
34
see
4
22
see
3–4
see also
10
restraint stress see stress
saline 22 49 50
34
see also
inhibitors
6
see
inhibitors
4
see also corticosteroids
stress 3–4
22
36
see
52
22
see
stimulation
63
see