Concentraciones de oxígeno intermitentes tienen impacto en el desarrollo postnatal temprano de ratas Sprague-Dawley: efectos en CA1 del hipocampo / Intermittent oxygen concentrations have an impact on the early postnatal development of Sprague-Dawley rats: effects on hippocampal CA1

El periodo postnatal temprano se caracteriza por rápido crecimiento cerebral, posiblemente relacionado con variaciones del oxígeno tisular. Esto ha motivado el estudio de protocolos que suministran diferentes concentraciones de oxígeno intermitentes, para observar sus efectos morfológicos y cerebrales. Se utilizaron 52 crías de ratas Sprague Dawley, distribuidas en igual número a cuatro grupos experimentales, Control (C, 21 %O2), Hipoxia Intermitente (HI, 11 %O2), Hiperoxia Intermitente (HOI, 30 %O2) e Hipoxia Hiperoxia Intermitente (HHI, 11 % -30 %O2). Los protocolos consideraron 5 ciclos de 5 minutos de dosificación, durante 50 minutos diarios. Se realizó en una cámara semihermética entre los días 5 al 11 postnatales. Las evaluaciones de crecimiento corporal y cuantificación neuronal, se realizaron en las crías macho, en el día 28 postnatal. El peso corporal en el grupo hipoxia intermitente mostró diferencias significativas respecto al grupo hiperoxia intermitente (HI vs HOI, p<0,01) y al grupo hipoxia-hiperoxia Intermitente (HI vs HHI, p< 0,001). La talla corporal disminuyó en el grupo hipoxia-hiperoxia intermitente con diferencias significativas respecto del grupo control (C vs HHI, p<0,05) y respecto del grupo hipoxia intermitente (HHI vs HI, p< 0,01). El conteo neuronal en el área CA1 del hipocampo aumentó en el grupo hipoxia intermitente con diferencias significativas respecto a los grupos control (C vs HI; p<0,05), al grupo hiperoxia intermitente (HI vs HOI; p<0,001) y al grupo hipoxia-hiperoxia intermitente (HI vs HHI; p<0,001). Finalmente, el grupo hipoxia- hiperoxia Intermitente disminuyó significativamente en la cantidad de neuronas en comparación al grupo hiperoxia intermitente (HHI vs HOI; p<0,001). La hipoxia intermitente mostró resultados beneficiosos en el crecimiento corporal y cantidad de neuronas en el área CA1 del hipocampo, en contraste, la hipoxia hiperoxia intermitente experimentó resultados adversos con disminución de estas variables, en el periodo postnatal temprano de la rata.

SUMMARY: The early postnatal period is characterized by rapid brain growth, possibly related to variations in tissue oxygen. This has motivated the study of protocols that supply different intermittent oxygen concentrations, to observe their morphological and cerebral effects. Fifty-two pups Sprague-Dawley rats were distributed in equal numbers into four experimental groups, Control (C, 21 %O), Intermittent Hypoxia (HI, 11 %O), Intermittent Hyperoxia (HOI, 30 %O2) and Intermittent Hypoxia Hyperoxia (HHI, 11 % - 30 %O2). The protocols considered 5 cycles of 5 min of dosing, for 50 min diary. It was performed in a semi- hermetic chamber between 5 to 11postnatal days. The evaluations of body growth and neuronal quantification were analyzed in male pups, on postnatal day 28. Body weight in the intermittent hypoxia group showed significant differences compared to the intermittent hyperoxia group (HI vs HOI, p<0.01) and the intermittent hypoxia- hyperoxia group (HI vs HHI, p<0.001). Body size decreased in the Intermittent hypoxia-hyperoxia group with significant differences compared to the control group (C vs HHI, p<0.05) and with respect to the intermittent hypoxia group (HHI vs HI, p<0.01). The neuronal count in the area CA1 of the hippocampus increased in the intermittent hypoxia group with significant differences compared to the control groups (C vs HI; p<0.05), to the intermittent hyperoxia group (HI vs HOI; p< 0.001) and the intermittent hypoxia-hyperoxia group (HI vs HHI; p<0.001). Finally, the intermittent hypoxia- hyperoxia group decreased significantly in the number of neurons compared with the intermittent hyperoxia group (HHI vs HOI; p<0.001). Intermittent hypoxia showed beneficial results in body growth and the number of neurons in the CA1 area of the hippocampus, in contrast, intermittent hypoxia-hyperoxia experienced adverse results with a decrease in these variables, in the early postnatal period of the rat.

Increased expression of the receptor for advanced glycation end products in neurons and astrocytes in a triple transgenic mouse model of Alzheimer's disease

The receptor for advanced glycation end products (RAGE) has been reported to have a pivotal role in the pathogenesis of Alzheimer's disease (AD). This study investigated RAGE levels in the hippocampus and cortex of a triple transgenic mouse model of AD (3xTg-AD) using western blotting and immunohistochemical double-labeling to assess cellular localization. Analysis of western blots showed that there were no differences in the hippocampal and cortical RAGE levels in 10-month-old adult 3xTg-AD mice, but significant increases in RAGE expression were found in the 22- to 24-month-old aged 3xTg-AD mice compared with those of age-matched controls. RAGE-positive immunoreactivity was observed primarily in neurons of aged 3xTg-AD mice with very little labeling in non-neuronal cells, with the notable exception of RAGE presence in astrocytes in the hippocampal area CA1. In addition, RAGE signals were co-localized with the intracellular amyloid precursor protein (APP)/amyloid beta (Abeta) but not with the extracellular APP/Abeta. In aged 3xTg-AD mice, expression of human tau was observed in the hippocampal area CA1 and co-localized with RAGE signals. The increased presence of RAGE in the 3xTg-AD animal model showing critical aspects of AD neuropathology indicates that RAGE may contribute to cellular dysfunction in the AD brain.