Relationship between androgen deficiency and memory impairment in aging and Alzheimer’s disease.

Aging and Alzheimer’s disease (AD) are associated with a declination of cognition and memory, whose severity increases in AD. Recent investigations point to a greater participation of neurofibrillary tangles (NFTs) than that of senile plaques, as responsible for cognitive impairment in AD and normal aging. On the other hand, aging is related with reduced levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) as well as testosterone (T). Basic and clinical studies give evidence that hypoandrogenism is associated with memory impairment. Accordingly, some animal studies show that the administration of these hormones improves the performance of cognitive tasks. However, effects of DHEA, DHEA-S, and T in the clinical setting, are not clear in part because of the balance between the benefits and risks of hormone therapy in aging subjects and because the cellular mechanism underlying its effects on memory in old age and related pathologies are unknown. The objective of this review is to analyze the role of DHEA, DHEA-S, and T, on memory in normal aging and in AD, and to determine whether these hormones modulate the hyperphosphorylation of tau protein, a molecular marker in AD pathology. The method used in the review included articles from the PubMed database, using the following search terms: DHEA, DHEA-S, T, memory, androgen deprivation therapy, tau protein, aging, and AD. Finally, we analyze the use of these steroids as an adjunct in the treatment of memory deficits in aging subjects and AD patients.

La deficiencia de andrógenos y su relación con el deterioro en la memoria en el envejecimiento y en la enfermedad de Alzheimer / Relationship between androgen deficiency and memory impairment in aging and Alzheimer's disease

El envejecimiento y la enfermedad de Alzheimer (EA) se asocian con una declinación de la cognición y la memoria, cuya gravedad aumenta en la EA. Varias investigaciones apuntan a una mayor participación de los ovillos neurofbrilares respecto a las placas seniles, como responsables del deterioro cognitivo en la EA y en el envejecimiento normal. Por otro lado, el envejecimiento se relaciona con una reducción en los niveles de dehidroepiandrosterona (DHEA) y su sulfato (DHEA-S), así como de testosterona (T); algunas evidencias básicas y clínicas indican que esta condición se asocia con deterioro en la memoria. Varios estudios en animales revelan que la administración de DHEA, DHEA-S y T mejoran la ejecución de tareas cognitivas. Sin embargo, el efecto de estas hormonas en el ámbito clínico no es claro, en parte por el balance entre los beneficios y los riesgos de una terapia hormonal en pacientes ancianos, así como por el desconocimiento de los mecanismos celulares que subyacen a sus efectos sobre la memoria en la vejez y en patologías relacionadas. El objetivo de esta revisión narrativa es analizar el papel de los esteroides DHEA, DHEA-S y T en la memoria en el envejecimiento normal y en la EA, así como la modulación en la hiperfosforilación de la proteína tau, un marcador molecular de la patología de la EA, por estas hormonas. El método empleado en esta revisión fue una búsqueda en la base de datos de Pubmed con los siguientes términos: DHEA, DHEA-S, T, memoria, terapia de privación de andrógenos, proteína tau, envejecimiento y EA. Finalmente, se analizará el empleo de estos esteroides como un coadyuvante en el tratamiento de las alteraciones de memoria en sujetos envejecidos y en pacientes con EA (AU)

Aging and Alzheimer's disease (AD) are associated with a declination of cognition and memory, whose severity increases in AD. Recent investigations point to a greater participation of neurofibrillary tangles (NFTs) than that of senile plaques, as responsible for cognitive impairment in AD and normal aging. On the other hand, aging is related with reduced levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) as well as testosterone (T). Basic and clinical studies give evidence that hypoandrogenism is associated with memory impairment. Accordingly, some animal studies show that the administration of these hormones improves the performance of cognitive tasks. However, effects of DHEA, DHEA-S, and T in the clinical setting, are not clear in part because of the balance between the benefits and risks of hormone therapy in aging subjects and because the cellular mechanism underlying its effects on memory in old age and related pathologies are unknown. The objective of this review is to analyze the role of DHEA, DHEA-S, and T, on memory in normal aging and in AD, and to determine whether these hormones modulate the hyperphosphorylation of tau protein, a molecular marker in AD pathology. The method used in the review included articles from the PubMed database, using the following search terms: DHEA, DHEA-S, T, memory, androgen deprivation therapy, tau protein, aging, and AD. Finally, we analyze the use of these steroids as an adjunct in the treatment of memory deficits in aging subjects and AD patients (AU)

Testosterona y salud mental: una revisión / Testosterone and mental health: a review

La testosterona es una hormona esteroide sintetizada a partir del colesterol en las células de Leydig de los testículos, y en menor concentración en las células de la teca del ovario y en la zona reticular de las glándulas suprarrenales. La testosterona interviene en la diferenciación testicular, cerebral y en el desarrollo de los caracteres sexuales primarios y secundarios. Además, modula la expresión de algunos comportamientos y rasgos de la personalidad, principalmente los relacionados con el mantenimiento del estatus social y con la reproducción. Por ejemplo, altas concentraciones de testosterona están asociadas con una mayor agresividad, competitividad, dominancia, libido sexual, búsqueda de pareja, entre otras. No obstante, la testosterona también ha sido asociada con algunos padecimientos relacionados con la salud mental, entre los que se encuentran los trastornos del estado de ánimo (ansiedad, depresión y trastorno bipolar), psicóticos (esquizofrenia) y trastornos de la personalidad. El objetivo del presente estudio fue realizar una revisión exhaustiva acerca de las principales investigaciones al respecto y ofrecer un panorama general sobre el papel de la testosterona en la incidencia de estos trastornos (AU)

Testosterone is a steroid hormone synthesized from cholesterol in the Leydig cells of the testes, and in lower concentrations in the theca cells of the ovary and the zona reticularis of the adrenal glands. Testosterone is involved in the differentiation of the brain and the testes and in the development of primary and secondary sexual characteristics. This hormone also modulates the expression of certain behaviours and personality traits, especially those related to the maintenance of social status and reproduction. For example, high levels of testosterone are associated with aggressiveness, competitiveness, dominance, sexual libido, seeking mate, etc. However, testosterone has also been associated with some disorders related to mental health, mainly the mood disorders (anxiety, depression and bipolar disorder), psychotic disorders (schizophrenia), and personality disorders. The aim of this study was to conduct an exhaustive review of the main research on the matter and to provide an overview on the role of testosterone in the incidence of those disorders (AU)

Cotransport of water by the Na+-K+-2Cl(-) cotransporter NKCC1 in mammalian epithelial cells.

Water transport by the Na+-K+-2Cl(-) cotransporter (NKCC1) was studied in confluent cultures of pigmented epithelial (PE) cells from the ciliary body of the fetal human eye. Interdependence among water, Na+ and Cl(-) fluxes mediated by NKCC1 was inferred from changes in cell water volume, monitored by intracellular self-quenching of the fluorescent dye calcein. Isosmotic removal of external Cl(-) or Na+ caused a rapid efflux of water from the cells, which was inhibited by bumetanide (10 µm). When returned to the control solution there was a rapid water influx that required the simultaneous presence of external Na+ and Cl(-). The water influx could proceed uphill, against a transmembrane osmotic gradient, suggesting that energy contained in the ion fluxes can be transferred to the water flux. The influx of water induced by changes in external [Cl(-)] saturated in a sigmoidal fashion with a Km of 60 mm, while that induced by changes in external [Na+] followed first order kinetics with a Km of about 40 mm. These parameters are consistent with ion transport mediated by NKCC1. Our findings support a previous investigation, in which we showed water transport by NKCC1 to be a result of a balance between ionic and osmotic gradients. The coupling between salt and water transport in NKCC1 represents a novel aspect of cellular water homeostasis where cells can change their volume independently of the direction of an osmotic gradient across the membrane. This has relevance for both epithelial and symmetrical cells.

Simultaneous measurement of water volume and pH in single cells using BCECF and fluorescence imaging microscopy.

Regulation and maintenance of cell water volume and intracellular pH (pHi) are vital functions that are interdependent; cell volume regulation affects, and is in turn affected by, changes in pHi. Disruption of either function underlies various pathologies. To study the interaction and kinetics of these two mechanisms, we developed and validated a quantitative fluorescence imaging microscopy method to measure simultaneous changes in pHi and volume in single cells loaded with the fluorescent probe BCECF. CWV is measured at the excitation isosbestic wavelength, whereas pHi is determined ratiometrically. The method has a time resolution of <1 s and sensitivity to osmotic changes of approximately 1%. It can be applied in real time to virtually any cell type attached to a coverslip, independently of cellular shape and geometry. Calibration procedures and algorithms developed to transform fluorescence signals into changes in cell water volume (CWV) and examples of applications are presented.