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David T Yew

Publications and source records attributed to David T Yew.

At least 19 recordsLinked to original sources

Changes of brain activity in the aged SAMP mouse.

This study investigates characteristics of aging in the central nervous system of the senescence accelerated prone mice (SAMP8). We examined 3 and 10-months old senescence-accelerated-prone mice (SAMP8) for functional and molecular changes in their brains, specifically in the hippocampus and somatosensory cortex. There was no statistically significant increase in the apoptosis indicators as revealed by Western Blotting for BAD and TUNEL experiments. However, the functional magnetic resonance imaging showed an increase in the area of BOLD images from the 3-month old to the 10-months old SAMP mice upon the application of tail stimulus. These results demonstrated a lack of neuronal deaths but an increase in the activated brain area with age.

Aging↗

Caspase-3 immunoreactivity in different cortical areas of young and aging macaque (Macaca mulatta) monkeys.

It has been shown that cytochrome-c-dependent caspase-3 activation is significantly elevated in the aging macaque brain. To assess the underlying age-related changes in the cellular distribution of caspase-3, we have examined the motor cortex, cerebellum and hippocampus of young (4-year-old, n = 4) and old (20-year-old, n = 4)rhesus monkeys by immunohistochemistry. Western blot analyses of brain homogenate showed that the antibody reacted only with inactive 32-kDa procaspase and its active 20- and 17-kDa subunits, formed after granzyme B exposure. In the motor cortex, pyramidal cells of layers III and V were moderately labeled; the underlying white matter contained weakly stained astrocytes. In the hippocampus, hilar neurons and pyramidal cells in CA3 showed the strongest immunoreaction, pyramidal cells in CA1 and granule cells of the dentate gyrus were also strongly labeled. In contrast, CA2 pyramidal cells were only weakly stained, and neurons of the molecular layer were unlabeled. Weak caspase-3 immunoreaction of CA2 neurons parallels known decreased susceptibility to apoptosis. In the cerebellar cortex, clusters of strongly labeled Purkinje cells were observed next to groups of weakly and unstained cells; granule cells were generally unstained. The brains of aging monkeys displayed a similar pattern of caspase-3 immunoreactivity. In neocortical layer V, however, scattered very strongly labeled pyramidal cells were regularly detected, which were not observed in younger animals. This clustering of caspase-3 indicates increased vulnerability of a subset of pyramidal cells in the aging brain.

Aging↗

Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients.

BACKGROUND: It has been hypothesized that alterations of the serotonergic system contribute to neuropsychiatric symptoms in Alzheimer disease (AD). Cellular expressions of the two serotonergic receptors 5-HT2A and 5-HT6 have therefore been determined by immunohistochemistry in the prefrontal cortex of patients with AD (n=6) and normal age-matched controls (n = 7). RESULTS: In normal aging patients, 5-HT2A label was mainly observed in large pyramidal cells, but to a lesser extent also in small pyramidal cells and in stellate cells of cortical layers II-VI. In AD, a similar distribution was observed, but density of positive cells was significantly reduced by 33%. In aging control patients, the 5-HT6 receptor was expressed by pyramidal cells and occasional stellate cells, not only of layers II-V, but also of layer I, where a distinct label was observed in neurons and surrounding fibers. 5-HT6 receptor expression in AD patients had the same pattern, but was significantly decreased by 40%. CONCLUSION: Our results indicate that a decline in neurons expressing 5-HT2A, but also 5-HT6 receptors may play a role in the etiopathology of neuropsychiatric symptoms in AD.

Aged↗

Immunohistological evidences of Ginkgo biloba extract altering Bax to Bcl-2 expression ratio in the hippocampus and motor cortex of senescence accelerated mice.

Ginkgo biloba extract 761 appears to display neuroprotective effect in many nervous diseases and aging. Deterioration of mental functions during aging is always accompanied by loss of neurons, presumably through apoptosis. Here, we studied the effect of G. biloba extract in the expression of Bax/Bcl-2 ratio, an important apoptotic index, in the hippocampus and motor cortex of the aging brain. Bax and Bcl-2 expressions were examined with immunohistochemical methods. Senescence Accelerated Mice Prone Strain 8 was used because the aging process was accelerated with neuropathological alterations similar to those found in the aging human brain. The mice were fed with either G. biloba extract or sucrose from the age of 3 weeks until sacrifice at 3 or 9 months old. In the hippocampus of G. biloba fed 9-month-old mice, the ratio of Bax positive cell to Bcl-2 positive cell (Bax/Bcl-2 expression ratio) was 11.43 +/- 3.11 (mean +/- SD); significantly lower (P < 0.05) than the Bax/Bcl-2 expression ratio of 20.99 +/- 5.34 in the sucrose fed mice. The Bax/Bcl-2 expression cell ratios, however, in the motor cortex were not significantly different between the two groups (2.22 +/- 1.35 versus 2.27 +/- 2.02 for the G. biloba and the sucrose fed mice, respectively). The decrease in the Bax/Bcl-2 expression cell ratio following G. biloba treatment might hence be able to protect the aging hippocampus from moving further down the apoptotic pathway. Western blotting confirmed the decrease of Bax in the brain even after a short term and high dose Ginkgo treatment. It is speculated that the G. biloba extract may be a potential neuroprotective agent against apoptosis through the differential expressions of the Bax and Bcl-2 in the hippocampus.

Animals↗

Diffusion tensor imaging (DTI) of rodent brains in vivo using a 1.5T clinical MR scanner.

PURPOSE: To evaluate the feasibility of using a clinical 1.5T MR scanner to perform magnetic resonance (MR) diffusion tensor imaging (DTI) on in vivo rodent brains and to trace major rodent neuronal bundles with anatomical correlation. MATERIALS AND METHODS: Two normal adult Sprague Dawley (SD) rats were anesthetized and imaged in a 1.5T MR scanner with a microscopic coil. DTI was performed at a resolution of 0.94 mm x 0.94 mm x 0.5 mm (reconstructed to 0.47 mm x 0.47 mm x 0.5 mm, with b-factors of 600 seconds/mm2 and 1000 seconds/mm2) and a higher resolution of 0.63 mm x 0.63 mm x 0.5 mm (reconstructed to 0.235 mm x 0.235 mm x 0.5 mm, with a b-factor of 1500 seconds/mm2). The fiber-tracking results were correlated with corresponding anatomical sections stained to visualize neuronal fibers. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the neuronal fibers were measured and compared with results in published reports. RESULTS: Several major neuronal fiber tracts, including the corticospinal cord, corpus callosum, and anterior commissure, were identified in all DTI data sets. Stained anatomical sections obtained from the rats confirmed the location of these fibers. The ADC values (0.6-0.8 +/- 10(-3) mm2/second) of the fibers were similar to published figures. However, the FA values (0.3-0.35) were lower than those obtained in previous studies of white matter in rodent spinal cord. CONCLUSION: We have demonstrated the feasibility of using a 1.5T clinical MR scanner for neuronal fiber tracking in rodent brains. The technique will be useful in rodent neuroanatomy studies. Further investigation is encouraged to verify the FA values generated by DTI with such techniques.

Animals↗

Immunohistochemical localization of endothelial isoform (eNOS) in human cerebral arteries and the aorta.

The common carotid, vertebral, posterior cerebral arteries, and the aorta were studied in the human in terms of its eNOS expression. In around 10 weeks of gestation, the developing intima began to express notable eNOS. In the adult, the positive eNOS sites were in the endothelial cells and the tunica media where the smooth muscles were. In the vessels with athrosclerotic changes, eNOS was down regulated in the endothelial layer and most of the tunica media but was significantly upregulated in the tunica media around the lesion. The protein changes are related to the onset of the athrosclerotic diseases.

Aged↗

Hypoxia-induced differential apoptosis in the central nervous system of the sturgeon (Acipenser shrenckii).

Hypoxia is a frequent challenge to aquatic vertebrates as compared with that for their terrestrial counterparts. All vertebrates respond to hypoxia in a similar, but not identical manner, indicating that these responses appeared early in the evolution of vertebrates. The aim of this study is to find out the effects of hypoxia on apoptosis in the central nervous system (CNS) of sturgeon, an archaic fish. With the regional specialization of the CNS, we hypothesize that if cell death does occur, the response will vary between regions, i.e., some CNS areas will be more susceptible to hypoxia than the others would. Sturgeons (Acipenser shrenckii) were subjected to hypoxia by exposure to either air or hypoxic water. After 6- or 30-h recovery they were sacrificed and the following regions of the CNS: retina, olfactory lobe, optic tectum, pituitary, cerebellum, pons/medulla, and spinal cord were examined by the terminal transferase mediated dUTP nick end labeling technique and for the cleaved fragment of activated caspase-3 by Western blotting. In hypoxia-treated sturgeons, the retina, optic tectum, pituitary, and spinal cord were found to have significantly more apoptotic cells than did untreated sturgeons at both 6 and 30 h after the hypoxic insults, indicating prolonged damage. Apoptosis was confirmed by Western blotting of the cleaved fragment of activated caspase-3. Olfactory lobe, cerebellum, and pons/medulla had relatively few apoptotic cells. The CNS of sturgeon showed a differential pattern of apoptosis in response to hypoxia.

Animals↗

The pattern of c-fos activation in the CNS is related to behavior in the mudskipper, Periophthalmus cantonensis.

The effects of three types of behavior on c-fos activation in different brain regions of the mudskipper, Periophthalmus cantonensis, were studied by immunocytochemistry. Animals were divided into four groups: The control group did not undergo any specific treatment. The second group consisted of animals that were agitated for an hour with a glass rod at an irregular speed. The third group contained animals showing aggressive behavior during an hour of monitoring, i.e. documented territorial hostility by raising of dorsal fins and pursuit of intruders. In contrast to these three groups, which had last been fed 24h earlier, the fourth group included animals that had been nourished 1h prior to sacrifice. Results showed that, in most brain regions of control animals, there were relatively few c-fos positive cells. After fish had been agitated, however, very prominent c-fos label was seen in the lateral and medial parts of the telencephalon, the thalamus, hypothalamus, pituitary and medulla. In aggressive fish, a significant increase in the number of c-fos positive sites, as compared to control fish, was observed in the diencephalons, pons and medulla, but not in the telencephalon. After feeding, there was a less substantial increase in c-fos protein expression in the diencephalon, but an even more prominent c-fos activation in the pons and medulla. Our present results support the hypothesis that, in fish, the medial telencephalon is involved in avoidance reaction and the lateral telencephalon in spatial memory, whereas rhombencephalic activation may reflect activity of cranial nerve nuclei.

Aggression↗

Changes of apoptosis-related proteins in hippocampus of SAM mouse in development and aging.

Expression of Caspase and Bcl-2 proteins was examined in the hippocampus of senescence-accelerated mice (SAM, P8 and R1 strain) from E19 to 16 months of age. Immunoblotting analysis showed no upregulation of pro-apoptotic proteins (caspase-2L, -3, -6, -8, -9, and Bax) with age while all the anti-apoptotic proteins (caspase-2S, Bcl-2, and Bcl-XL) remained unchanged during aging. Terminal dUTP nick end labeling (TUNEL) and electron microscopy on the hippocampus of 3- and 16-month-old SAM revealed very few TUNEL positive cells in both groups. Morphometric study further showed neuronal loss in the hippocampus was not age-related. Our results suggest apoptosis and cell loss are minor events in the hippocampus of SAM mice and are unlikely to be the cause of functional decline during aging in SAM.

Aging↗

fMRI mapping of cortical centers following visual stimulation in postnatal pigs of different ages.

Classical studies have demonstrated that the visual centers in primates consist of cortical areas V1, V2 and V4 and their branches. However, nothing is known about how these visual areas change in postnatal development. In the present studies, therefore, pigs aged 2, 4, and 6 months old, were stimulated visually with a colored checker board and the active sites in the cortex, cerebellum and brainstem recorded using functional magnetic resonance imaging (fMRI). In pigs aged 2 months old, visual stimulation induced an increase in activation of sites in the V2 and V4 cortical areas, as well as in the areas of the inferior aspect of the parietal and middle aspect of the temporal cortices, but not in the medial and caudal occipital cortex (V1 area). At 4 months old, the V1 area was also activated, and by 6 months old, an inferior sector in the prefrontal cortex was also activated. As the pigs aged, functional active sites were further demonstrated in the cerebellum and the brainstem, which probably had to do with action memory, and the control of the ocular muscles, respectively. It is concluded that the visual pathway of the pig mainly involves cortical areas that mature at 6 months of age.

Aging↗

N-methyl-D-aspartate receptor and apoptosis in Alzheimer's disease and multiinfarct dementia.

This study investigates the role of excitotoxicity in Alzheimer's disease and in multiinfarct dementia by examining, via immunohistochemical methods, the number of cells that are positive for N-methyl-D-aspartate (NMDA) receptor and the degree of colocalization between NMDA receptor and apoptosis markers such as TUNEL or activated caspase-3 in the frontal cortex of individuals with these two conditions, comparing the results with those from subjects who died of normal aging. We showed an increased number of NMDA receptor-positive cells and an increased number of TUNEL-labeled cells in the frontal cortex of subjects with Alzheimer's disease, especially in the deeper layers of the cortex. However, only about 10% of cells showed colocalization of NMDA receptor with the apoptosis markers studied, suggesting that NMDA-mediated excitotoxicity does not play a major role in neuronal apoptosis in Alzheimer's disease or in multiinfarct dementia.

Aging↗

Dedifferentiation of adult human myoblasts induced by ciliary neurotrophic factor in vitro.

Ciliary neurotrophic factor (CNTF) is primarily known for its important cellular effects within the nervous system. However, recent studies indicate that its receptor can be highly expressed in denervated skeletal muscle. Here, we investigated the direct effect of CNTF on skeletal myoblasts of adult human. Surprisingly, we found that CNTF induced the myogenic lineage-committed myoblasts at a clonal level to dedifferentiate into multipotent progenitor cells--they not only could proliferate for over 20 passages with the expression absence of myogenic specific factors Myf5 and MyoD, but they were also capable of differentiating into new phenotypes, mainly neurons, glial cells, smooth muscle cells, and adipocytes. These "progenitor cells" retained their myogenic memory and were capable of redifferentiating into myotubes. Furthermore, CNTF could activate the p44/p42 MAPK and down-regulate the expression of myogenic regulatory factors (MRFs). Finally, PD98059, a specific inhibitor of p44/p42 MAPK pathway, was able to abolish the effects of CNTF on both myoblast fate and MRF expression. Our results demonstrate the myogenic lineage-committed human myoblasts can dedifferentiate at a clonal level and CNTF is a novel regulator of skeletal myoblast dedifferentiation via p44/p42 MAPK pathway.

Animals↗

A fMRI study of age-related differential cortical patterns during cued motor movement.

Healthy adults of three age groups (young, middle-age and older) were cued by a multimedia projector to perform a series of simple (making a fist, opening/closing of the mouth) and complex (opposition of index finger and thumb, chewing gum) motor tasks while being scanned by functional magnetic resonance imaging. Our results showed that in unilateral hand movements, the premotor/motor cortex in the contralateral hemisphere was most strongly activated. Supplementary motor cortex involvement was usually present in the young and not in the old, except in precision movement when supplementary motor cortex was also involved in the old. For movements of the face (chewing, opening and closing of mouth), the prefrontal cortex was activated in the old age group but finger and hand movements never activated the prefrontal cortex in any age. Furthermore, areas like insula and cingulate gyrus might be activated in motor tasks. We conclude that different motor activities triggered diverse activation patterns which differed in different age groups.

Adult↗

The postnatal development of the cerebellum- a fMRI and silver study.

The aim of this study was to evaluate the postnatal development of the cerebella of the pig and to compare this with the activation of the fMRI. The cells in the cerebella were studied by silver technique and the activation of the fMRI in the cerebella was initiated by flexion and extension of the hind paw. Our results showed an increase of the branching of the cells of the cerebellar cortex postnatally, coordinated with registration of fMRI active sites in the cerebella at 6-month postnatal. We concluded that the full maturation of the cerebella was around 6-month postnatal in the pig.

Animals↗

Age related changes of various markers of astrocytes in senescence-accelerated mice hippocampus.

Astrocytes play a critical role in maintaining normal brain physiology during development and in adulthood, while to date the changes of astrocytes during aging and their effects on age-related functional decline have not been well understood. This study used immunohistochemistry, western blot, and reverse transcriptase polymerase chain reaction techniques to investigate the expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and S100 beta proteins and mRNAs in the hippocampi of 3 months old and 16 months old senescence-accelerated-prone mice (SAMP8) and senescence-accelerated-resistant mice (SAMR1). The results showed significant age-related increases in both protein and mRNA levels of GFAP in the hippocampi of aged SAMP8 and SAMR1. As well, the GFAP of aged SAMP8 was significantly greater than that of aged SAMR1. However, no such increase was observed for either GS or S100 beta. These results suggested that GFAP, rather than GS or S100 beta, played a more important role in the age related deficits in learning and memory.

Aging↗

Postmortem changes in the central nervous system and adrenal medulla of the heroin addicts.

This study describes the pathological changes in 20 heroin addicts (12 male and 8 female) autopsied 24 h after sudden death. The central nervous system (including the pituitary body) and the adrenal medulla were studied, along with those from age-matched controls who died from traffic accidents. Immunohistochemistry and histological (Hematoxylin and eosin) observation were performed. Some neuronal cells in every region of the CNS were positive for opioid receptors but these cells were most numerous in the hippocampus. Positive opioid fibers were most abundant in the basal ganglia region. Histopathology indicated coagulative changes of cytoplasm and dissolution of Nissl bodies of neuron. Edema of nerve fibers was frequently demonstrated. Pituitary body showed an evident decrease or even absence of basophils in the pars anterior. The adrenal medulla featured a down regulation of chromaffin granules. Degeneration of CNS neurons and fibers, alterations in hormonal and blood pressure regulation therefore would be the prime targets of heroin addiction in human subjects.

Adrenal Medulla↗

bcl2, bax, and nestin in the brains of patients with neurodegeneration and those of normal aging.

This study was conducted by employing specimens from the frontal cortices of Alzheimer, multiple-infarct dementia patients, and those of normal aging (age matched to patients). The objective was to evaluate and compare the bcl2, bax, and nestin patterns in these three groups. Using immunocytochemistry, it was observed that bcl2 and bax active sites were colocalized in 45% of cells in Alzheimer, 52% of cells in multiple infarct, and 30% of cells in normal aging. bcl2 and bax could also be separately located in cells of all three groups. bax cells were most prominent in number in Alzheimer patients and least prominent in normal aging. nestin was found in all three groups but was most prominent in the multiple-infarct patients. Both astrocytes and neurons demonstrated positive nestin sites. The difference in pattern between groups will lead to further understanding of cellular changes in neurodegenerative patients and those of normal aging.

Aged↗