Presentation given by Vicente Felipo from Príncipe Felipe Research Center in the framework of the Emergence Forum Barcelona Biocat organized the Barcelona Emergence Forum (April 10-11th, 2014, Congress Palace, Montjuïc) supported by the TRANSBIO SUDOE, a translational cooperation project dedicated to innovation in life sciences in South-West Europe. The Barcelona Emergence Forum contributed to bringing together Academics, Companies, Investment Entities, Technology Platforms and Technology Transfer Offices from Spain, France and Portugal to set up collaborative projects on Human Health & Agro-food Innovation. More information at: http://www.b2match.eu/emergenceforum2014

1. 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/

2. 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

3. 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

4. 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

5. 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

6. 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.

7. 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.

8. 0 2 4 6 8 10 12 14 16 18 20 22 24 26
0
200
400
600
800
1000
1200 CONTROL
HA
*** ***
***
**
** *
ZT
Ambulatorycounts
MOTOR
COORDINATION
Beam walking
Rotarod
MOTOR ACTIVITY
Circadian rhythms
AnxietyWheels

9. 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

10. 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

11. 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
Ca
2 +
Glu
CM
N O
.
GC
cGMP
Ca
2+
cGMP
NOS

12. 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

13. LABORATORY OF
NEUROBIOLOGY
Vicente Felipo vfelipo@cipf.es
Programa
Prometeo GV
SAF