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R Verduga

Publications and source records attributed to R Verduga.

14 recordsLinked to original sources

Chronic treatment with a precursor of cellular phosphatidylcholine ameliorates morphological and behavioral effects of aging in the mouse [correction of rat] hippocampus.

Normal aging is commonly associated with a decline in memory, mainly for that related with newly acquired information. The hippocampal formation (HF) is a brain region that has been implicated in this dysfunction. Within the HF there are several cellular types, such as pyramidal cells, granule neurons of the dentate gyrus, and astrocytes. CDP-choline is a well-known intermediate in the biosynthesis of phosphatidylcholine, a phospholipid essential for neuronal membrane preservation and function; thus, this compound would attenuate the process of neuronal aging. To test this, three groups of male mice were used in this study. An adult 12-month-old group (ACG), a 24-month-old (OCG), and an old experimental group (OEG) were administered orally a solution of CDP-choline (150 mg/kg per day) from 12 up to 24 months. Experimental observations suggest that CDP-choline has a positive effect on memory (reference errors were attenuated), and hippocampal morphology resembled that of younger animals.

Aging↗

Cholinergic, serotonergic and catecholaminergic neurons are not affected in Ts65Dn mice.

Ts65DN mice were developed as a model of Down syndrome (DS); they are trisomic for the distal segment of chromosome 16 (MMU16), which contains genes syntenic with some of the genes located on the critical region of human chromosome 21 (HSA21). Since behavioral and neurochemical disturbances have been observed in this animal model, it seemed interesting to perform an immunohistochemical characterization of the main cholinergic, catecholaminergic and serotonergic nuclei. However, when the brains of Ts65Dn mice were compared with those of control littermates, no differences were found either in the morphology of the neurons of the three systems or in the number of immunoreactive cells. The results indicate that these systems are not affected by the triplication of some of the genes present on chromosome 16.

Animals↗

Neurons co-localizing calretinin immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the hippocampus and dentate gyrus of the rat.

Co-localization of calretinin immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity was studied in the rat hippocampus and dentate gyrus. Neurons co-expressing both markers (CR/NADPH-d) were observed throughout the hippocampus and dentate gyrus. However, they were more abundant in the stratum pyramidale and radiatum of CA3, stratum pyramidale of CA1, and in the juxtagranular zone of the hilus. The NADPH-d activity appeared in 37% of the calretinin immunoreactive neurons in CA3, 42% in CA1, and 36% in the dentate gyrus, whereas calretinin immunoreactivity occurred in 41% of the NADPH-d positive neurons in the hippocampus, and 16% in the dentate gyrus. The morphology and location of the double marked cells could not be used as a characteristic of the co-localizing neurons. The heavily stained NADPH-d neurons occurring mainly in CA1 do not show calretinin immunoreactivity. NADPH-d fiber swellings could be observed in close apposition to calretinin immunoreactive neurons and dendrites, suggesting synaptic contacts. It has been reported that calretinin immunoreactivity and NADPH-d activity co-localize infrequently in other areas such as the neocortex, striatum, hypothalamus and tegmental nucleus. The relatively high proportion of double marked cells found in the hippocampus and dentate gyrus could be indicative of the importance of the CR/NADPH-d interneurons in the circuitries of these areas.

Animals↗

Effects of chronic administration of cytidine-5'-diphosphate choline (CDP choline) on the aged female mouse Harderian gland.

The effect of chronic intake of cytidine-5'-diphosphate choline (CDP choline), a precursor of the membrane lipid phosphatidylcholine, was analyzed in secretory cells of the Harderian gland (HG) of aged (26-month-old) female Swiss mice. These mice were treated with the drug from 12 months of age until they were 26 months old. The results obtained were compared with those of an age-matched control group and another adult (12-month-old) control group. In both control groups, the HGs displayed secretory tubules formed by a single squamous epithelium of lipid-secreting cells. The tubule lumens were occupied by numerous small pleomorphic porphyrin accretions. In contrast, the tubules of the CDP-choline-treated animals consisted of a single columnar epithelium, with lipid-secreting cells filled with lipid vacuoles. The most striking feature in the HGs of the CDP-choline group was the absence of prophyrin deposits. These observations indicate that porphyrin biosynthesis in female Swiss mice is maintained even in very old animals, and that chronic administration of CDP choline prevents porphyrin deposition in the HG of aged animals.

Aging↗

Differences between the circadian system of two strains of senescence-accelerated mice (SAM).

The aim of this study was to look for morphological or functional differences between the circadian system of two substrains of Senescence Accelerated Mice (SAM): senescence-prone (SAMP8; average median survival time = 10.0 months) and senescence-resistant (SAMR1; average median survival time = 18.9 months). Neither the general structure nor the quantitative analysis of the number of VP-positive neurons in matched sections revealed differences between SAMP8 and SAMR1 mice. Under LD 12/12 photoperiod, all animals showed the typical pattern of wheel running activity with maximum activity in the first half of darkness period. The period of the locomotor activity in free running as well as the time course for synchronization after a 6 h phase delay of LD cycle were similar in both strains of SAM mice. However, SAMP8 animals reentrained significantly earlier (3.4 +/- 0.4 days) than SAMR1 (6.3 +/- 0.9 days) after a 6 h phase advance of LD cycle. We conclude that the circadian system of SAMP8 mice presents some functional differences with that of SAMR1, which could help to explain their different rate of ageing.

Aging↗

Effects of melatonin on the proliferation and differentiation of human neuroblastoma cells in culture.

Since melatonin has direct inhibitory effects on some tumor cells in vitro, the aim of the present work was to study whether the growth and structural characteristics of the human neuroblastoma cell line SK-N-SH in vitro are influenced by this indoleamine. Concentrations of melatonin of 10(-9) and 10(-11) M significantly inhibited (P < 0.05) cell proliferation. Subphysiological (10(-13) M) or supraphysiological (10(-7) and 10(-5) M) concentrations of melatonin lacked this effect. After 8 days of exposure to melatonin (10(-9) M), cells showed significantly smaller cell and nuclear sizes than control cells. Melatonin-treated cells presented greater neurite outgrowth than control cells. These results support the hypothesis that melatonin, at physiological concentrations, exerts a direct antiproliferative effect on SK-N-SH cells, promoting the differentiation of neuroblastoma cells.

Analysis of Variance↗

Structural changes induced by cytidine-5'-diphosphate choline (CDP-choline) chronic treatment in neurosecretory neurons of the supraoptic nucleus of aged CFW-mice.

The influence of chronic administration of cytidine-5'-diphosphate choline (CDP-choline), a precursor of the membrane lipid phosphatidylcholine, was studied in neurosecretory neurons (NSNs) of the supraoptic nucleus (SON) of aged mouse hypothalamus. Animals were treated with CDP-choline from 12 months of age until 26 months. They were studied for both morphologic and morphometric features. The results obtained were compared to those of an age-matched control group. There was evidence of differences between NSNs of the control group and those of the CDP-choline group which showed neuronal hypertrophy. This size increase was mainly attributed to the increment of cellular protein synthesis machinery, rough endoplasmic reticulum (RER) and Golgi complexes. Furthermore there was an increase in the number of neurosecretory granules (NSGs) in the CDP-choline group. In addition, there was no tertiary lysosomes in the treated animals. Moreover, the percentage of NSN membrane that was not covered by glial prolongations, increased from about 2% in the control group to 12% in the CDP-Choline treated group. These changes suggested an activation of the cellular processes for neurohormone synthesis in the experimental group. Furthermore, these NSNs displayed lipid droplets in their cytoplasm. The possible relationship between CDP-choline and NSNs activity is discussed.

Aging↗

Dimorphic myelin in the rat optic nerve as a result of retinal activity blockage by tetrodotoxin during early postnatal period.

The effects of the retinal ganglion cell (RGC) activity blockage on the early myelination of the rat optic nerve (ON) were investigated at the light and ultrastructural levels. The blockage of the RGC action potential was attained by the use of tetrodotoxin (TTX), a blocker of the voltage-sensitive sodium channels. TTX was either infused directly into the left eye (TON) or injected systematically (SON). These two groups of ONs were compared with the untreated paired right nerves (UON) of the eye-infused group. Our observations showed that the general morphology of the ONs in either treated group was similar to that of the UONs. The most noticeable ultrastructural feature of these nerves was the presence of dimorphic myelin sheaths in 4% of the myelinated fibres (MFs) in the TON group at postnatal day twelve, while they were seldom observed in the other groups (0.5%). These abnormal covers were of two types; long flaps of aberrant myelin or redundant myelin profiles. However, at postnatal day seven, the onset of myelination and the percentage of MFs was similar in the three groups. The morphometric results showed that there were no age-group differences in axon size in unmyelinated and MFs. These results suggest that while the bioelectrical activity of the RGCs could not play any role in maintaining axon calibre it may, to some extent, regulate the process of formation of normal myelin sheaths in the rat ON.

Animals↗

The influence of age on supraoptic nucleus glial cells of the mouse.

In 2-year-old mice, astrocytes of the supraoptic nucleus (SON) of the hypothalamus, placed in close contact with the meningeal covering contained concentric arrangements of cisterns in their cytoplasm called glial concentric bodies (GCBs). They are formed by a variable number of flattened cisterns without pores, and no anastomosis was observed between adjacent cisterns. Rough endoplasmic reticulum (RER) cisterns do not show continuity with fully developed GCBs, although a close continuity between RER cisterns and GCBs was present in images suggesting GCB formation. Concomitantly with the appearance of GCBs, ventral neurosecretory neurons of the SON showed a cytoplasmic membrane reinforced by the apposition of glial prolongations. The possible origin and function of these GCBs and lamellae are discussed here.

Aging↗

Interaction between melatonin and estradiol on morphological and morphometric features of MCF-7 human breast cancer cells.

Melatonin has been shown to have a direct inhibitory effect on the proliferation of estrogen-responsive MCF-7 human breast cancer cells, involving an interaction with estradiol. The anti-proliferative effect of melatonin is reversed by the addition of estradiol to the culture. In the present study, we examined whether inhibition by melatonin and subsequent estrogen rescue of MCF-7 cells are correlated with morphological and morphometric changes in these cells. After 4 days of exposure to melatonin, MCF-7 cells showed significantly smaller cell and nuclear sizes than other groups. These morphometric results were closely related to the ultrastructural features observed in these cells. While control and estradiol-treated cells showed increased tumor characteristics, melatonin-treated cells presented greater differentiation, in keeping with their epithelial origin (presence of cytokeratin filament bundles, conspicuous rough endoplasmic reticulum, and Golgi cisternae together with the presence of prominent nucleoli at the nuclear level). Additionally, some melatonin-treated cells displayed degenerative features (mitochondrial swelling with disruption of cristae, cytoplasmic vacuolation, nuclear chromatin disgregation and cell lysis). The addition of estradiol to cells previously incubated with melatonin reversed the changes induced by the latter and these cells showed the same ultrastructural features as the control cells. Our results support the notion that melatonin exerts its antitumor effect through a cell-cycle-specific mechanism by delaying the entry of MCF-7 cells into mitosis. This allows the tumor cells to achieve greater differentiation. The fact that the morphometric and morphological effects induced by melatonin are counteracted by estrogens suggests a cell-cycle acceleration induced by estradiol.

Breast Neoplasms↗

Probable acenocoumarol-amoxycillin interaction.

We present the case of a woman undergoing treatment with acenocoumarol for deep vein thrombosis, who maintained an international normalized ratio (INR) of between 2.5 and 4 for 2 months. Seven days after the introduction of amoxycillin (500 mg/8 h) for a probable respiratory infection, the patient developed spontaneous bruising, with an INR of 7.1. Treatment with amoxycillin was discontinued, and 3 weeks later the INR had returned to previous values. In this case, the increase in the INR value with associated bruising after the addition of amoxycillin suggests a drug interaction between acenocoumarol and amoxycillin, other possible causes having been eliminated.

Acenocoumarol↗