NEUROPLASTICITYNew Biochemical Mechanisms

Editors-in-chief

With contributions from

CONTENTS

iv

iv

CONTRIBUTOR BIOGRAPHIES

Jorge Alberto Costa e Silva

-

Jean-Paul Macher

v

Jean-Pierre Olié

-

-

l’Encephale and member of the

-

Eberhard Fuchs

-

v

vi

vi

-

Lawrence Reagan

Jim Fadel

and Leah Reznikov

vii

vii

Bruce McEwen

-

-

The Hostage Brain

The End

of Stress as We Know It

Thérèse Jay

viii

viii

The European Journal of Psychiatry and Frontiers in Neuroscience

-

Philip Gorwood

Psychopharmacogenetics

European Psychiatry

FOREWORD

Neuroplasticity

-

second edition of Neuroplasticity — New Biochemical Mechanisms

-

-

-

-

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Neuroplasticity

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

-

-

-

-

Figure 1.

Debranching is prevented by

Figure 2.

A

B

C

Control Stress Control Stress

Control Stress

A B

C

III Depression and reduced hippocampal volume

-

-

to chronic stress have been used to understand the cellular mechanisms

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IV Structural plasticity beyond the hippocampus

-

Figure 3.

Stress, depression Antidepressant treatment

� �� �� ��� �� �

-

-

neurochemical mechanisms could mediate the dendritic alterations seen

Figure 4.

Prefrontal cortex

���

Hippocampus

����

Amygdala

�

metabolism

��

V Structural plasticity of glutamatergic axons

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VI The impact of glia

-

-

Figure 5.

Steroid hormones

VII Conclusions

References

1

2

3

4

5

6

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8

9

10

11

12

13

14

15

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18

19

20

21 -

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31

32

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33

34

35 -

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36

GLUTAMATE-MEDIATED NEUROPLASTICITY DEFICITS IN MOOD DISORDERS

Leah R. Reznikov, Jim R. Fadel

and Lawrence P. Reagan

I Introduction

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-

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II The glutamatergic system

-

-

-

N D

III Glutamatergic projections and anatomical substrates

of mood-related disorders

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-

-

-

-

-

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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.

V Understanding glutamate’s involvement in neuroplasticity:

functional implications in relation to psychiatric illness

-

Figure 1.

-

Prefrontal Cortex

Hippocampus

Amygdala

Long-term potentiation

-

-

Morphological plasticity

-

-

-

-

-

-

-

Treatment implications

-

Figure 2.

-

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

-

-

VI Conclusions

References

1

2 -

3

4

5

6 -

7

8

9 -

10

11 -

12

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46 N D

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68

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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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-

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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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-

-

-

-

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VIII Relationships between AMPA receptor phosphorylation

and antidepressant effect

-

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

-

-

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

IX Conclusions

References

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3

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CELLULAR PLASTICITY AND THE PATHOPHYSIOLOGY OF DEPRESSION

Thérèse M. Jay

I Introduction

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-

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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

-

-

VI Effects of stress on glutamatergic neurotransmission

in the hippocampus

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

-

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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

-

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

-

X Conclusions

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 (

%)

References

1

2 -

3

4

5

6

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7

8

9

10 -

11

12

13

14

15 -

16

17

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25

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69

Philip Gorwood

I Introduction

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II Relevency of stress in the model of depression regarding the role of europlasticity

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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

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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

-

-

-

VI Conclusions

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References

1

2

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3

4 -

5

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6 -

7

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8 -

9

10 -

11 -

12

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13

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14

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15

an N D

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17

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21 -

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30 -

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37 -

38

39

40

41

42

43

44

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

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