1. Acelerated clinical course of prion
desease in mice compromised in
repair of oxidative DNA damage.
Clara M.O. Jalland, Sylvie L. Benestad, Cecilie Ersdal, Katja
Scheffler, Rajikala Suganthan. Yusaku Nakabeppu, Lars Eide,
Magnar Bjoras, Michael A. Tranulis.

2. INTRODUCTION:
PRION
Infectious
agent
Are not living
organisms
Acumulates
in infected
tissues
Compossed by a
modify protein
They could
propagate
Tissue damage
and cell death
Misfolded
protein

3. INTRODUCTION
• PRION REPLICATION:

4. DNA
DNA
damages
damages
Exogenous
Exogenous
Endogenous
Endogenous
Oxidation of
Oxidation of
bases
bases
Alquilation
Alquilation
of bases
of bases
Hydrolysis
Hydrolysis
of bases
of bases
Mismatch of
Mismatch of
bases
bases

5. DNA REPAIR:
Is a set of processes by which the cell identifies and corrects
damage done to the DNA molecules that encode the genome
Base excision repair
Cutting the double
helix.

6. GENERAL OBJECTIVE
OBSERVATE AND REPORT THE PROGRESSION OF
EXPERIMENTAL PRION DISEASE IN MICE WITH
COMPROMISE DNA- REPAIR CAPCITY

7. MATERIALES Y METODOS
El estudio fue llevado a cabo en concordancia con el
reglamento noruego sobre experimentación animal.
Aprobado por el comité de ética para experimentación con
animales del instituto nacional de veterinaria de Noruega.

8. 12
WILDTYPE
30
RATONES
18
TRANSGENICOS
Criterios de inclusión: ratones hembra que pesaran 20g al
momento de la inoculación.

9. INOCULO:
Todos los ratones
Todos los ratones
excepto los control
excepto los control
fuero inoculados
fuero inoculados
con RML aislado.
con RML aislado.

10. DISEÑO EXPERIMENTAL:
Ratones
Anestesiados
e inoculados
Monitoreados
PrPsc yy
PrPsc
GFAP
GFAP
Inmuno
Inmuno
histoquímica
histoquímica
Corte
Corte
longitudinal del
longitudinal del
encéfalo
encéfalo
PrPsc
PrPsc
Western Blot
Western Blot
Congelación del
Congelación del
otro hemisferio
otro hemisferio
Sacrificados
Extracción de
órganos

11. INMUNOHISTOQUIMICA
Utilizada para
Utilizada para
identificar moléculas
identificar moléculas
especificas en cualquier
especificas en cualquier
clase de tejido, donde
clase de tejido, donde
hay una relación
hay una relación
antígeno- anticuerpo.
antígeno- anticuerpo.
Esto se puede ver al
Esto se puede ver al
microscopio cuando se
microscopio cuando se
utiliza una reacción
utiliza una reacción
colorante.
colorante.

12. INMUNOHISTOQUIMICA:

13. WESTERN BLOT:
Las proteínas procedentes de
extractos celulares son separadas por
electroforesis, por medio de la
técnica SDS-PAGE. Tras este proceso
las proteínas se transfieren a un filtro
donde hay anticuerpos que
reaccionan con la proteínas de
interés.

14. PCR EN TIEMPO REAL:
• Plataforma ideal para el desarrollo de pruebas
moleculares para identificación y
cuantificación de agentes infecciosos de
interés clínico.
• Los procesos de amplificación y detección se
realizan en simultanea.

16. RESULTADOS

17. RESULTADOS

18. RESULTADOS

19. DISCUSSION
AUTHOR
WHAT DID HE SAY
THEY ARE AGREE? YES OR
NO
(Akhtar, S. et al. 2013 ;Tamguney,
G. et al. 2008).
“Many previous studies have
identified genetic elements that
influence the incubation period of
experimental prion disease”
YES
(Guentchev, M et al, 2002)
The direct contribution of ROS to
the pathogenesis
of prion diseases is somewhat less
explored; however, analysis of
brain areas in humans affected by
CJD showed increased levels of
oxidative DNA damage
YES

20. DISCUSSION
AUTHOR
WHAT DID HE SAY
(Sandberg, M.K. et al 2011)
“the morphological end-point of
prion disease provides little
information about the rapidity of
clinical deterioration in the toxic
phase of prion disease.”
YES
(Brown, D. R. et al. 1997 ; Brown,
D. R et al. 2002).
“Interestingly, an antioxidant
YES
function has been ascribed to the
cellular prion protein PrPC.”
THEY ARE AGREE? YES OR
NO

21. CONCLUSIONS
This item is important to note that ROS cause more
damage to specific parts of the body such as the
brain, considering that produces neurodegenerative
diseases, it is important to sensitize the population
on the production of ROS, which although they are
synthesized by the organism inevitably, there are
other situations that stimulate their production and
can be avoided. Is important to note as the PRP may
be a protective factor for susceptibility to oxidative
stress.
It is important with this article to see what the real
effect of the ROS, Prion organism level and mainly
they attack not only generate alterations in DNA but
almost all components of the organism such as
proteins, lipids, in the nucleus, mitochondria.

22. CONCLUSIONS
•
It is important to do these studies to elaborate
It is important to do these studies to elaborate on the alterations and diseases that can be triggered
on the alterations and diseases that can be
starting with a mutation or alteration alteration
triggered starting with a mutation or in DNA, since diseases are usually of great significance when they
start there since way to cure them and the only we can do is observe their progress
in DNA, is no diseases are usually of great
significance when they start there is no way to
cure them and the only we can do is observe
their progress
This article is useful because ititallows us to
This article is useful because allows us to
recognize the natural mechanisms that make the
recognize the natural mechanisms that make the
body to correct the errors caused by agents such as
body to correct the errors caused by agents such as
ROS in DNA, which in this case is injury escicion
ROS in DNA, which in this case is injury escicion
bases and genes are related in this repair as is
bases and genes are related in this repair as is
MUTYH and OGG1 and the severe impact that may
MUTYH and OGG1 and the severe impact that may
have on the body ififany of these suffers aafailure,
have on the body any of these suffers failure,
usually producing tumor lesions.
usually producing tumor lesions.

23. MAPA CONCEPTUAL:

24. MAPA CONCEPTUAL:

25. BIBLIOGRAFIA:
•
MARTINEZ S, Lina María; VARGAS G, Natalia; TORO M, Andrés
Eduardo; PAMPLONA S, Ana Paulina, QUEVEDO O, Esteban. Biología
Molecular. 5. ed. Medellín. Colombia. UPB, Facultad de medicina.
2012.