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.

INTRODUCTION:

PRION

Infectious agent

Compossed by a modify protein

Are not living organisms

They could propagate

Acumulates in infected

tissues

Tissue damage and cell death

Misfolded protein

INTRODUCTION

• PRION REPLICATION:

DNA damages

DNA damages

Endogenous Endogenous

ExogenousExogenous Oxidation of bases

Oxidation of bases

Alquilation of bases

Alquilation of bases

Hydrolysis of bases

Hydrolysis of bases

Mismatch of bases

Mismatch of bases

GENERAL OBJECTIVE

OBSERVATE AND REPORT THE PROGRESSION OF EXPERIMENTAL PRION DISEASE IN MICE WITH

COMPROMISE DNA- REPAIR CAPCITY

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.

12 WILDTYPE

30 RATONES

18 TRANSGENICOS

Criterios de inclusión: ratones hembra que pesaran 20g al momento de la inoculación.

INOCULO:

Todos los ratones excepto los control

fuero inoculados con RML aislado.

Todos los ratones excepto los control

fuero inoculados con RML aislado.

DISEÑO EXPERIMENTAL:

Ratones Anestesiados e inoculados

Monitoreados Sacrificados

Extracción de órganos

Corte longitudinal del

encéfalo

Corte longitudinal del

encéfalo

Inmuno histoquímica

Inmuno histoquímica

Congelación del otro hemisferio

Congelación del otro hemisferioWestern BlotWestern Blot

PrPsc y GFAP

PrPsc y GFAP

PrPscPrPsc

INMUNOHISTOQUIMICA

Utilizada para identificar moléculas

especificas en cualquier clase de tejido, donde

hay una relación antígeno- anticuerpo. Esto se puede ver al

microscopio cuando se utiliza una reacción

colorante.

Utilizada para identificar moléculas

especificas en cualquier clase de tejido, donde

hay una relación antígeno- anticuerpo. Esto se puede ver al

microscopio cuando se utiliza una reacción

colorante.

INMUNOHISTOQUIMICA:

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.

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.

RESULTADOS

RESULTADOS

RESULTADOS

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 pathogenesisof prion diseases is somewhat less explored; however, analysis of brain areas in humans affected by CJD showed increased levels of oxidative DNA damage

YES

DISCUSSION

AUTHOR WHAT DID HE SAY THEY ARE AGREE? YES OR NO

(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 function has been ascribed to the cellular prion protein PrPC.”

YES

CONCLUSIONS

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.

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.

CONCLUSIONS

• It is important to do these studies to elaborate on the alterations and diseases that can be triggered

starting with a mutation or alteration in DNA, since 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

It is important to do these studies to elaborate on the alterations and diseases that can be

triggered starting with a mutation or alteration in DNA, since 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 it allows us to recognize the natural mechanisms that make the

body to correct the errors caused by agents such as ROS in DNA, which in this case is injury escicion bases and genes are related in this repair as is

MUTYH and OGG1 and the severe impact that may have on the body if any of these suffers a failure,

usually producing tumor lesions.

This article is useful because it allows us to recognize the natural mechanisms that make the

body to correct the errors caused by agents such as ROS in DNA, which in this case is injury escicion bases and genes are related in this repair as is

MUTYH and OGG1 and the severe impact that may have on the body if any of these suffers a failure,

usually producing tumor lesions.

MAPA CONCEPTUAL:

MAPA CONCEPTUAL: