PHARMACOLOGIE DE LA COGNITION

1
PHARMACOLOGIE DE LA COGNITION

•  Des Neurosciences à la Prescription 
• Hervé ALLAIN
• Stéphane SCHUCK
• Nicolas MAUDUIT
• Université de Rennes I

2
HYPOTHESIS EFFECTS OF DRUGS ON COGNITIVE
FUNCTIONS ?

• Quantitative Performance
• Positive Clinical trials
• Négative Pharmacovigilance
• Qualitative Distortion
• ex Anxiety Drugs, hallucinogens

3
WHAT ARE COGNITIVE FUNCTIONS ?

• Intellectual functions definition of human
  being
• Language
• Learning
• Memory
• Decision-Making
• Action Planing
• Waiting capacity ...

4
HOW TO EXPLORE THE COGNITION ?

• Experimental psychology
• Neuropsychology
• Neuroimaging
• Neurochemistry
• Signals and data analysis
• Computer sciences
• Philosophy

5
INFORMATION PROCESSING MODEL OF COGNITION

• Environment Attention Cognition
  Emotion Memory
• Reward
• Behaviour Responses
• All those steps are within the brain

Motivation
6
(No Transcript)
7
PREREQUISITES FOR A PHARMACOLOGY OF COGNITON

• Genetics
• Neurobiology
• Tools for cognition measurement
• Drug cognitive mapping

8
Rationale for a Pharmacology of Cognition (1)

• Daily living
• Decision-making/choice
• Use of computers, telephones
• Quality of life
• Learning at school
• Socialization
• Pathology
• Psychiatry
• Alzheimer s disease

9
Rationale for a Pharmacology of Cognition (2)

• Law
• Accidents
• Catastrophs
• Violence
• Suicide
• Bioethics
• Phineas Gage (Damasio)

10
GENETICS AND COGNITIVE FUNCTION (I)

• Molecular basis of single-gene disorders or
  chromosomal abnormalities gt cognitive impairment
  (mental retardation)
• Mapping and cloning gene variants gt variation in
  intellectual abilities (dyslexia)
• Mutations in mice gt models (memory)

11
Examples of the duo genetics/cognition

• Four-generation family impairment in grammar
  (plural of words inflected forms of regular
  verbs)
• Grammar genes ! (Pinker, 1994)
• Dyslexia inability to recognize phonemes/6 p
  21.3 (reading-related locus)

12
A link between genetics and conventional
neurobiology

• Non-specific mental retardation
• 3 genes GDI1, oligophrenin, PAK 3
• Involved in Rho GTPase signalling networks
• development of axonal connections
• neurotransmitter release
• recruitment of synaptic vesicles for exocytose
• formation of dendrites
• Alzheimer s disease
• ApoE/Ach neurons/plasticity

13
Neurobiology of cognition (I)

• Neurotransmission
• Second-messengers
• Transcription factors
• Gene

14
Neurobiology of cognition (II)

• Function localisation
• Electrophysiology
• Neurochemistry
• Genetics
• An example learning and memory

15
(No Transcript)
16
(No Transcript)
17
Biologie moléculaire de l apprentissage et de la
mémorisation
18
Aperçu historique

• Tacrine, Cognex, 1994
• Levodopa, 1960
• Riluzole, Rilutec, 1998

• Alois Alzheimer, 1907, 1 cas
• James Parkinson, 1817, 6 cas
• Jean Martin Charcot, 1878

19
Les médicaments des MN
20
Anomalies génétiques / conséquences

• Mutations
• Gain de fonction toxique pour les cellules
• répetition de triplets CAG (résidus de glutamine)
• Perte d une fonction, manque d une protéine
• exemple de l Ataxie de Friedreich
• Conséquences
• Tout concourt à la mort cellulaire probablement
  par apoptose ( chute des feuilles en automne).
  Activation des gènes de mort cellulaire

21
La sérotonine

• Neuromédiateur clédans la migraine
• Récepteurs 5-HT1B / 5-HT1D
• impliqués dans laction thérapeutique DHE et
  Triptans

22
(No Transcript)
23
La migraine les structures en cause
Cerveau
Ganglion
Tronccérébral
V
24
(No Transcript)
25
(No Transcript)
26
(No Transcript)
27
(No Transcript)
28
Intellects artificiels  Artilects 

• Circuits électroniques
• loi de Moore
• taille d une molécule
• Ingénierie évolutive
• Field programmable gate arrays
• Algorithmes génétiques
• Le cerveau artificiel (Hugo de Garis)

29
Les acteurs rennais
Neurologie (Pr Edan, Pr Vérin)
Gériatrie (Pr Jouanny)
Psychologie (Pr Lieury)
Biotrial (JM Gandon)
Pharmacologie (Pr Allain, Dr Schück) Essais
cliniques Pharmaco-épidémiologie Pharmacovigilance
Epidémiologie (Pr Chaperon) Informatique
médicale Pr Lebeux
30
(No Transcript)
31
CONCLUSION

• Pharmacological approaches of CNS diseases
  through cognitive processes
• Quick switch from a receptor tointelligence!
• Decision and choice of drugs
• Future new drugs

32
Colin Mc Ginn

•  The water of the physical brain is turned into
  the wine of consciousness 
• (from Brains to consciousness, Steven Rose,
  1998)
• www.med.univ-rennes1.fr/etud/pharmaco