Expression and prognostic significance of apolipoprotein D in breast cancer.

En esta publicación se evaluó la expresión y la significación pronostica de la apolipoproteína D (apo D) en 163 carcinomas mamarios. La apo D es una glicoproteína involucrada en el sistema de transporte de lípidos del plasma humano y presente en grandes cantidades en el líquido de los quistes de mujeres con enfermedad macroquistica mamaria. Además, se ha propuesto como marcador de la acción esteroidea en células de cáncer de mama. La técnica empleada para evaluar la expresión de Apo D en carcinomas de mama fue la tinción con inmunoperoxidasa. Del total, 103 tumores se tiñeron para la apo D con una amplia variabilidad en la intensidad y el porcentaje de positividad. Para la cuantificación de la tinción se utilizó el sistema HSCORE que considera tanto la intensidad de la tinción como el porcentaje de células teñidas. Los resultados de este estudio mostraron una asociación significativa entre la apo D y el estado menopáusico de pacientes y el grado de diferenciación de los tumores. Los valores de apo D fueron más bajos en tumores de mujeres premenopáusicas o en carcinomas pobremente diferenciados, sugiriendo el valor potencial de esta glicoproteína como factor pronóstico en cáncer de mama. Además, el análisis preliminar de supervivencia libre de enfermedad y supervivencia global en un subgrupo de 152 mujeres con un seguimiento medio de 42 meses confirmó que los valores bajos de apo D se asociaban significativamente con una supervivencia libre de enfermedad más corta y una supervivencia global más pobre. No encontramos ninguna correlación significativa entre la apo D y el tamaño del tumor, la afectación de los ganglios linfáticos o parámetros bioquímicos como los receptores de estrógenos, la catepsina D o la proteína pS2. Los resultados de este estudio fueron muy trascendentes ya que nos permitieron proponer que la apo D, en combinación con otros factores pronósticos bien establecidos, podría contribuir a identificar con mayor precisión a subgrupos de pacientes con cáncer de mama con bajo o alto riesgo de recaída y muerte. La importancia de esta publicación se ha visto refrendada en publicaciones recientes donde se ha corroborado que esta lipoproteína está relacionada con la gravedad del cáncer de mama

Cuprizone-Induced Neurotoxicity in Human Neural Cell Lines Is Mediated by a Reversible Mitochondrial Dysfunction: Relevance for Demyelination Models

Suitable in vivo and in vitro models are instrumental for the development of new drugs aimed at improving symptoms or progression of multiple sclerosis (MS). The cuprizone (CPZ)-induced murine model has gained momentum in recent decades, aiming to address the demyelination component of the disease. This work aims at assessing the differential cytotoxicity of CPZ in cells of different types and from different species: human oligodendroglial (HOG), human neuroblastoma (SH-SY5Y), human glioblastoma (T-98), and mouse microglial (N-9) cell lines. Moreover, the effect of CPZ was investigated in primary rat brain cells. Cell viability was assayed by oxygen rate consumption and by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based (MTT) method. Our results demonstrated that CPZ did not cause death in any of the assayed cell models but affected mitochondrial function and aerobic cell respiration, thus compromising cell metabolism in neural cells and neuron-glia co-cultures. In this sense, we found differential vulnerability between glial cells and neurons as is the case of the CPZ-induced mouse model of MS. In addition, our findings demonstrated that reduced viability was spontaneous reverted in a time-dependent manner by treatment discontinuation. This reversible cell-based model may help to further investigate the role of mitochondria in the disease, and study the molecular intricacies underlying the pathophysiology of the MS and other demyelinating diseases. Keywords: neurodegenerative diseases, copper chelator, pathophysiology, cell metabolism, gli

Apolipoprotein D synthesis progressively increases in frontal cortex during human lifespan

Apolipoprotein D (apo D) is a lipocalin present in the nervous system that may be related to processes of reinnervation, regeneration and neuronal cell protection. In the other way, apo D expression has been correlated, in some brain regions, with normal aging and neurodegenerative diseases. To elucidate the regional and cellular expression of apo D in normal human brain during aging, we performed a detailed and extensive study in samples of post-mortem human cerebral cortices. To achieve this study, slot blot techniques, for protein and mRNA, as well as immunohistochemistry and hybridohistochemistry methods were used. A positive correlation for apo D expression with aging was found; furthermore, mRNA levels, as well as the protein ones, were higher in the white than in the grey matter. Immunohistochemistry and non-isotopic HIS showed that apo D is synthesized in both neurons and glial cells. Apo D expression is notorious in oligodendrocytes but with aging the number of neurons that synthesize apo D is increased. Our results indicate that apo D could play a fundamental role in central nervous system aging and in the reduction of products derivated from lipid peroxidation. The increment in the expression of apo D with aging can be included in a global mechanism of cellular protection to prevent the deleterious effects caused by aging

Regional and gender study of neuronal density in brain during aging and in Alzheimer’s disease

Background: Learning processes or language development are only some of the cognitive functions that differ qualitatively between men and women. Gender differences in the brain structure seem to be behind these variations. Indeed, this sexual dimorphism at neuroanatomical level is accompanied unequivocally by differences in the way that aging and neurodegenerative processes affect men and women brains. Objective: The aim of this study is the analysis of neuronal density in four areas of the hippocampus, and entorhinal and frontal cortex to analyze the possible gender influence during normal aging and in Alzheimer’s disease (AD). Methods: Human brain tissues of different age and from both sexes, without neurological pathology and with different Braak’s stages of AD, were studied. Neuronal density was quantified using the optical dissector. Results: Our results showed the absence of a significant neuronal loss during aging in non-pathological brains in both sexes. However, we have demonstrated specific punctual significant variations in neuronal density related with the age and gender in some regions of these brains. In fact, we observed a higher neuronal density in CA3 and CA4 hippocampal areas of non-pathological brains of young men compared to women. During AD, we observed a negative correlation between Braak’s stages and neuronal density in hippocampus, specifically in CA1 for women and CA3 for men, and in frontal cortex for both, men and women. Conclusion: Our data demonstrated a sexual dimorphism in the neuronal vulnerability to degeneration which suggest the need to consider the gender of the individuals in future studies, regarding neuronal loss in aging and AD, in order to avoid problems in interpreting data

Apolipoprotein D expression absence in degenerating neurons of human central nervous system

Apolipoprotein D (apo D), a lipocalin transporter of small hydrophobic molecules could play an important role in several neurodegenerative diseases. However, its role in those diseases remains unclear. There has been reported increments of apo D in relation with different neuropathologic diseases. Recently, we reported the absence of apo D in neurons of substantia nigra which can contribute to the lability of neurons to oxidative damage. In order to determine the relationship between apo D expression and neuronal death, we studied the expression of apo D in various regions of human brains from patients without any neurological or psychological disorders, in relation with the neuronal damage revealed by Fluoro-Jade B staining. The absence of expression for apo D in injured neurons and the negative staining for Fluoro-Jade B of neurons that express apo D was observed in all sections studied. These findings are in accordance with the role possibly played by apo D in the neuroprotection of the nervous system