MILD COGNITIVE AND MOTOR IMPAIRMENT:

ASSESSMENT, MECHANISMS AND

TREATMENT

Vicente Felipo

Laboratory of Neurobiology, NEUROCIPF

Centro de Investigación Príncipe Felipe

Valencia, Spain

vfelipo@cipf.es

http://www.neurocipf.es/

AIMS:

In animal models:

1. Unveil the molecular mechanisms leading

to cognitive / motor impairment

2. Identify new therapeutic targets for its

treatment

3. Design and assess new therapeutic

procedures to reverse cognitive / motor

impairment

AIMS:

4. To study in patients the

mechanisms, diagnosis and

treatment of neurological

impairment

5. Bring to the clinic the therapeutic

procedures developed in animal models

6. Identify early diagnostic procedures for

neurological impairment

7. Bring to the clinic the diagnostic

procedures identified

In patients

Identifying biomarkers in blood and

develop tools for early diagnosis of

cognitive impairment at preclinical

stage.

Perform psychometric tests assessing

different cognitive and motor functions:

attention, visuo-motor coordination,

bimanual coordiantion, mental porcessing

speed, etc

We have identified the first

peripheral biomarker (3-nitro-

tyrosine in serum) to diagnose

minimal hepatic encephalopathy

in patients with liver cirrhosis.

The procedure has been

patented

We wish to develop a

diagnostic tool

We perform the following types of studies:

1 Analysis of cognitive and motor

functions in rats

2 Study of the alterations of cognitive and motor

functions in pathological situations and of the

mechanisms responsible for the alterations.

3 Evaluation of therapeutic treatments to restore

the cognitive and/or motor functions.

4 Analysis of the possible secondary effects of

drugs on cognitive and motor function.

5 Analysis of circadian rhythms of activity

and of their alterations in pathological

situations or by the use of drugs

6 Analysis of the electroencephalogram (EEG)

and of their alterations in pathological situations

or by the use of drugs

7 . Analysis of a wide variety of compounds in

blood, brain or other tissues by different techniques

(HPLC, immunohistochemistry, western blott, ELISA, etc):

inflammatory markers, neurotransmitters, amino acids,

neurosteroids, nitrotyrosine, markers of oxidative stress,

any protein by immunoblotting, nitration of proteins, etc.

0 2 4 6 8 10 12 14 16 18 20 22 24 260

200

400

600

800

1000

1200CONTROL

HA

*** ***

*****

** *

ZT

Am

bu

lato

ry c

ou

nts

MOTOR

COORDINATION

Beam walking

Rotarod

MOTOR ACTIVITY

Circadian rhythms

Anxiety Wheels

Y maze, conditional

discrimination

Spatial learning and memory,

Morris water maze

Spatial learning and

memory, Radial maze

Object recognition

Object location

Active / passive

avoidance

COGNITIVE FUNCTION

NEUROLOGICAL

ALTERATIONS

Motor activity

Motor coordination

Learning Y maze

MOLECULAR

MECHANISMS INVOLVED

Dopamine-glutamate

neurotransmission in NAcc

GABA neurotransmission

in cerebellum

Function of the glutamate-

NO-cGMP pathway

in cerebellum

Y maze conditional discrimination test

Modulated by the Glu-NO-cGMP

pathway

Experim Control

The walls may be white or

black. When they are white,

food is put on the right;

when they are black, on the

left. Rats must learn where

is the food depending on the

color of the wall

Ca2 +

Glu

CM

N O

. GC

cGMP

Ca2 +

cGMP

NOS

COOPERATION OFFERED includes, but not restricted to:

1) Participate as partners in European or other

projects. We have long expertise and have provided

this type of studies in 8 different European projects.

2) Provide this type of studies to pharmaceutical or

other type of companies as a service to test

beneficial effects of new drugs (or secondary

effects). We have also experience in this type of

collaboration.

3) Collaboration in research projects of interest

vfelipo@cipf.es

http://www.neurocipf.es

LABORATORY OF

NEUROBIOLOGY Vicente Felipo vfelipo@cipf.es

Programa

Prometeo GV

SAF