[Cellular prion protein in the central nervous system of mammals. Anatomoclinical associations]. / La proteína priónica celular en el sistema nervioso central de mamíferos. Correlatos anatomoclínicos.

INTRODUCTION: The scrapie prion protein (PrPsc) requires the cellular prion protein (PrPc) for its propagation and replication. In this work we studied the expression and localization of the PrPc in the central nervous system (SNC) of the rat, mouse, cat, cow and human, using immunohistochemistry and Western blot techniques to understand more about prionopathies and Alzheimer's disease (EA). MATERIAL AND METHODS: For the immunohistochemistry study we used human, cat, rat and cow samples to analyse frontal, temporal and occipital cortex, as well as the hippocampus and the thalamus. For the Western blot analysis we used mouse, cat, cow and human brain samples. RESULTS: We observed a decrease in the amount of PrPc in the SNC in a rostrocaudal shift in the species mentioned above. We observed inhibitory cells in the cat cortex. The Western blot analysis showed a similar pattern of expression in the different species studied with a preponderance of the diglycosylated band, in relation to the other bands observed in the analysis. DISCUSSION: These data suggest that in prionopathies PrPsc could be transmitted and could be replicated in and from the areas with most expression of PrPc. Similarly, a higher amount of this protein (PrPc) in some brain areas could explain some histopathological aspects of EA. CONCLUSIONS: Our findings support the hypothesis of a retrograde transport of PrPsc in the SNC. PrPc could be related to the pathophysiology of EA.

The cellular prion protein and its role in Alzheimer disease.

The cellular prion protein (PrP(C)) is a membrane-bound glycoprotein especially abundant in the central nervous system (CNS). The scrapie prion protein (PrP(Sc,) also termed prions) is responsible of transmissible spongiform encephalopathies (TSE), a group of neurodegenerative diseases which affect humans and other mammal species, although the presence of PrP(C) is needed for the establishment and further evolution of prions. The present work compares the expression and localization of PrP(C) between healthy human brains and those suffering from Alzheimer disease (AD). In both situations we have observed a rostrocaudal decrease in the amount of PrP(C) within the CNS, both by immunoblotting and immunohistochemistry techniques. PrP(C) is higher expressed in our control brains than in AD cases. There was a neuronal loss and astogliosis in our AD cases. There was a tendency of a lesser expression of PrP(C) in AD cases than in healthy ones. And in AD cases, the intensity of the expression of the unglycosylated band is higher than the di- and monoglycosylated bands. With regards to amyloid plaques, those present in AD cases were positively labeled for PrP(C), a result which is further supported by the presence of PrP(C) in the amyloid plaques of a transgenic line of mice mimicking AD. The work was done according to Helsinki Declaration of 1975, and approved by the Ethics Committee of the Faculty of Medicine of the University of Navarre.

[Anatomical basis of sleep]. / Bases anatómicas del sueño.

Sleep is an active and periodic biological state composed of NREM and REM phases, which alternate during the night. Both biological clocks and specific neurotransmitters are involved in the modulation of this system. It is a complex neuronal network in which several areas of the central nervous system are involved. The oneiric processes are also controlled neurally. This work summarises the history of the investigations on this topic from the 19th century to date. It is worth mentioning the recent findings of Lugaresi and colleages who described fatal familial insomnia, a disease that helped to show the importance of the mediodorsal thalamic nucleus in the genesis of slow-wave sleep. Reinoso s group found out that the paramedian ventral area of the oral pontine reticular nucleus is the conductor in the establishment of REM sleep.

Bases anatómicas del sueño / Anatomical basis of sleep

El sueño es un estado biológico activo, periódico, en el que se distinguen las etapas NREM y REM, que se alternan sucesivamente durante la noche. Intervienen los relojes biológicos en la modulación del sistema, así como neurotransmisores específicos. Se trata de una red neuronal compleja, en la que intervienen diversas zonas del sistema nervioso central. Los procesos oníricos están controlados además de forma neural. Se resume la historia de las investigaciones sobre el tema, desde el siglo XIX hasta nuestra época. Hay que destacar los recientes descubrimientos de Lugaresi y su equipo, que, al describir el insomnio familiar grave, dieron importancia al núcleo dorsomedial del tálamo en la instauración de la fase de sueño profundo. Al grupo de Reinoso se debe el hallazgo de que el “director de orquesta” en la instauración del sueño REM es la zona ventral paramediana del núcleo reticular pontino oral

Sleep is an active and periodic biological state composed of NREM and REM phases, which alternate during the night. Both biological clocks and specific neurotransmitters are involved in the modulation of this system. It is a complex neuronal network in which several areas of the central nervous system are involved. The oneiric processes are also controlled neurally. This work summarises the history of the investigations on this topic from the 19th century to date. It is worth mentioning the recent findings of Lugaresi and colleages who described fatal familial insomnia, a disease that helped to show the importance of the mediodorsal thalamic nucleus in the genesis of slow-wave sleep. Reinoso´s group found out that the paramedian ventral area of the oral pontine reticular nucleus is the conductor in the establishment of REM sleep

[Expression and localization of the cellular prion protein (PrPc) in the cow's central nervous system. Some reflections on the nvCJD]. / Expresión y localización de la proteína priónica celular (PrPC) en el sistema nervioso central de la vaca. Algunas reflexiones sobre la nvCJD.

INTRODUCTION: The appearance of bovine spongiform encephalopathy (BSE) and its involvement in the generation of the new variant of Creutzfeldt-Jakob Disease (nvCJD) had important implications from a social and economical point of view. As the presence of PrPC is necessary to establish prion diseases and for the replication of PrPSC in BSE, the study of the expression and localization of PrPC in the central nervous system of cow, mainly the brainstem, is interesting itself. MATERIAL AND METHODS: Expression of PrP by western blot technique and its precise localization by immunohistochemistry were analyzed in the central nervous system of the autochthonous pyrenees breed, a group of cows with a high incidence for BSE. RESULTS: PrP was more abundantly expressed in rostral areas rather than caudal regions of the cow brain. Immunohistochemistry was congruent with western blotting studies. Localization of PrPC was particularly abundant in the cerebral cortex, hippocampus, etc. Noteworthy, immunopositivity was present in the dorsal motor nucleus of the vagus and the hypoglossal nucleus. The anterior horn of the spinal cord yielded higher labelling for PrP than the posterior horn. CONCLUSION: PrPC is more abundantly expressed in rostral areas of the central nervous system. According to the findings observed in other mammal species, presence of PrPC in motoneurons of cow indicates that PrPSc might be transported from its site of entry to the central nervous system following a retrograde direction.

Expresión y localización de la proteína priónica celular (PrPC) en el sistema nervioso central de la vaca. Algunas reflexiones sobre la nvCJD / Expression and localization of the cellular prion protein (PrPc) in the cow's central nervous system. Some reflections on the nvCJD

Introducción. La repercusión económica y social de la encefalopatía espongiforme bovina (EEB) y su relación con la nueva variante de la enfermedad de Creutzfeldt-Jakob (nvCJD) hace interesante un estudio de la expresión y localización de la proteína priónica celular (PrPC) en el sistema nervioso central de la vaca, con especial atención al tronco del encéfalo, especialmente alterado en la EEB. Según varios autores la presencia PrPC es esencial para el establecimiento y replicación del prión (PrPSc), presente en la EEB. Material y métodos. Se utilizaron muestras de encéfalos de vacas de raza autóctona pirenaica. Se estudió la expresión de PrP mediante técnicas de wester blot, así como la localización de PrPC en el sistema nervioso central, con especial atención al tronco del encéfalo. Resultados. La expresión y cuantificación de PrP fue mayor en zonas rostrales que en caudales. La inmunohistoquímica fue concordante con el western. La localización de PrPC era importante en corteza cerebral, hipocampo, etc. Se destacó inmunopositividad notable en el núcleo motor dorsal del nervio vago y en el del nervio hipogloso. El asta anterior de la médula cervical era más inmunopositiva que el asta posterior. Conclusión. Existe una mayor abundancia de PrPC en zonas rostrales que en caudales del sistema nervioso central de la vaca. Debido a la presencia de PrPC en neuronas motoras, y de acuerdo con hallazgos en otras especies de mamíferos, la transmisión de la PrPSc se haría retrógradamente desde su vía de acceso y en el interior del sistema nervioso central (AU)

Introduction: The appearance of bovine spongiform encephalopathy (BSE) and its involvement in the generation of the new variant of Creutzfeldt-Jakob Disease (nvCJD) had important implications from a social and economical point of view. As the presence of PrPC is necessary to establish prion diseases and for the replication of PrPSC in BSE, the study of the expression and localization of PrPC in the central nervous system of cow, mainly the brainstem, is interesting itself. Material and methods: Expression of PrP by western blot technique and its precise localization by immunohistochemistry were analyzed in the central nervous system of the autochthonous pyrenees breed, a group of cows with a high incidence for BSE. Results: PrP was more abundantly expressed in rostral areas rather than caudal regions of the cow brain. Immunohistochemistry was congruent with western blotting studies. Localization of PrPC was particularly abundant in the cerebral cortex, hippocampus, etc. Noteworthy, immunopositivity was present in the dorsal motor nucleus of the vagus and the hypoglossal nucleus. The anterior horn of the spinal cord yielded higher labelling for PrP than the posterior horn. Conclusion: PrPC is more abundantly expressed in rostral areas of the central nervous system. According to the findings observed in other mammal species, presence of PrPC in motoneurons of cow indicates that PrPSc might be transported from its site of entry to the central nervous system following a retrograde direction (AU)