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Jennifer A. Fike Cecilia A. Hennessy Michael L. Kennedy Olin E. Rhodes Jr 《Conservation Genetics Resources》2013,5(3):679-681
The eastern gray squirrel (Sciurus carolinensis) often serves as a model organism for investigations of wildlife ecology. The authors developed 11 polymorphic microsatellite markers to facilitate future research questions. The number of alleles per locus ranged from three to ten and observed heterozygosities ranged from 0.143 to 0.786. Interspecific screening revealed that several loci were polymorphic in Sciurus niger (eight loci) and Tamiasciurus hudsonicus (four loci). These markers will aid in investigations of movements, social structure and mating tactics of eastern gray squirrel populations. 相似文献
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Yani Zou Rikki Corniola David Leu Aslam Khan Peyman Sahbaie Ayanabha Chakraborti David J. Clark John R. Fike Ting-Ting Huang 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(52):21522-21527
Cranial irradiation is widely used in cancer therapy, but it often causes cognitive defects in cancer survivors. Oxidative stress is considered a major cause of tissue injury from irradiation. However, in an earlier study mice deficient in the antioxidant enzyme extracellular superoxide dismutase (EC-SOD KO) showed reduced sensitivity to radiation-induced defects in hippocampal functions. To further dissect the role of EC-SOD in neurogenesis and in response to irradiation, we generated a bigenic EC-SOD mouse model (OE mice) that expressed high levels of EC-SOD in mature neurons in an otherwise EC-SOD–deficient environment. EC-SOD deficiency was associated with reduced progenitor cell proliferation in the subgranular zone of dentate gyrus in KO and OE mice. However, high levels of EC-SOD in the granule cell layer supported normal maturation of newborn neurons in OE mice. Following irradiation, wild-type mice showed reduced hippocampal neurogenesis, reduced dendritic spine densities, and defects in cognitive functions. OE and KO mice, on the other hand, were largely unaffected, and the mice performed normally in neurocognitive tests. Although the resulting hippocampal-related functions were similar in OE and KO mice following cranial irradiation, molecular analyses suggested that they may be governed by different mechanisms: whereas neurotrophic factors may influence radiation responses in OE mice, dendritic maintenance may be important in the KO environment. Taken together, our data suggest that EC-SOD plays an important role in all stages of hippocampal neurogenesis and its associated cognitive functions, and that high-level EC-SOD may provide protection against irradiation-related defects in hippocampal functions.Cranial irradiation is widely used as a treatment modality for patients with primary or metastatic brain tumors (1–3), and is also used as a prophylactic treatment to prevent metastases of high-risk tumors to the nervous system (4). Although effective, cranial irradiation is associated with various complications or side effects in cancer survivors (1–3). One of the severe complications is neurocognitive impairment, which can include defects in executive functions and learning and memory (3). Neurocognitive impairments occur in both adults and children and are generally associated with higher doses and younger age (3). The pathogenesis of radiation-induced neurocognitive impairment is not completely understood, but recent studies suggest that suppressed hippocampal neurogenesis (5, 6), increased hippocampal neuronal apoptosis (7, 8), and reduced growth hormone secretion (9, 10) may be involved.The production of reactive oxygen species (ROS) is considered a major cause of radiation-induced tissue damage (11). Ionizing irradiation not only results in the acute generation of short-lived ROS, it also results in a persistent state of oxidative stress that extends up to several months or even years after irradiation (12, 13). Accordingly, animal and cell models with altered antioxidant capacities have been used to investigate the biochemical pathways involved in radiation-induced tissue and cell injuries, and experimental antioxidant-based therapies have been designed to protect normal tissues during radiation treatments (14).Hippocampal neurogenesis is important for hippocampal-dependent functions of learning and memory and the process is exquisitely sensitive to suppression by various stressors, including radiation and oxidative stress (5, 6, 15). To determine if altered redox balance in the hippocampal microenvironment affects hippocampal neurogenesis and the associated functions of learning and memory, we used a knockout mouse model (KO) deficient in the extracellular antioxidant enzyme, EC-superoxide dismutase (EC-SOD), in an earlier study with cranial irradiation (13, 16). When examined at 3–4 mo of age, EC-SOD deficiency was associated with a significant suppression of baseline neurogenesis and impaired hippocampal-dependent cognitive functions (13, 16). Unexpectedly, EC-SOD deficiency also rendered the process less sensitive to radiation-induced changes. The underlining mechanism for this paradoxical finding was not clear, but preliminary studies ruled out up-regulation of major antioxidant enzymes (13). The results suggested that the interaction between redox balance and irradiation and their effects on hippocampal functions can be complex, and understanding how these elements work in concert may be a key to identifying strategies for radioprotection.To manipulate redox balance in the hippocampus, we generated a mouse model with inducible EC-SOD transgenes (17). In the current study, we combined the inducible transgenes with EC-SOD KO and generated a bigenic mouse model, designated as the overexpressor (OE), with high levels of EC-SOD expressed only in Ca/calmodulin-dependent protein kinase- (CaMKII) positive neurons in an otherwise EC-SOD–deficient environment (17). Hippocampal neurogenesis generates new granule cells that are functionally integrated into the hippocampal network (18). Because granule cells are CaMKII-positive neurons and are the principal excitatory neurons in the dentate gyrus, the manipulation leads to an estimated four- to fivefold increase in EC-SOD activity in the hippocampal formation in OE mice (17). The OE mice were used to investigate the effects of altered EC-SOD levels at different stages of hippocampal neurogenesis and the functional consequences of learning and memory. Comparison between WT, OE, and KO mice revealed the importance of EC-SOD in progenitor cell proliferation, dendritic development, and long-term survival of newborn neurons. The study results also suggested that maintenance of the dendritic system following cranial irradiation was important for preservation of neurocognitive functions. 相似文献
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Sara J. Oyler-McCance Jennifer A. Fike Todd A. Castoe Diana F. Tomback Michael B. Wunder Taza D. Schaming 《Conservation Genetics Resources》2013,5(2):303-305
Clark’s nutcrackers are important seed dispersers for two widely-distributed western North American conifers, whitebark pine and limber pine, which are declining due to outbreaks of mountain pine beetle and white pine blister rust. Because nutcracker seed dispersal services are key to maintaining viable populations of these imperiled pines, knowledge of movement patterns of Clark’s nutcrackers helps managers understand local extinction risks for these trees. To investigate population structure within Clark’s nutcracker, we developed primers for and characterized 13 polymorphic microsatellite loci. In a screen of 22 individuals from one population, levels of variability ranged from 6 to 15 alleles. No loci were found to be linked, although 4 loci revealed significant departures from Hardy–Weinberg equilibrium and evidence of null alleles. These microsatellite loci will enable population genetic analyses of Clark’s nutcrackers, which could provide insights into the spatial relationships between nutcrackers and the trees they help disperse. 相似文献
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J R Fike E L Gillette D J Clow 《International journal of radiation oncology, biology, physics》1979,5(3):339-342
Neovascularization was induced surgically in normally avascular canine corneas to study the repair of sublethal damage in slowly proliferating capillary endothelial cells. Neovascularization was stimulated for 7 days after split dose treatments with 6Co γ-rays. Corneal tissue samples were evaluated by quantitative morphometric methods. A time recovery curve was drawn by plotting per cent capillary volume vs time between two equal doses. A typical “Elkind type” of time recovery response was observed. A split dose response assay resulted in an incremental dose D2—D1 of 265 rad at the 1% capillary volume level. The results suggest a substantial repair capacity for capillary endothelial cells. 相似文献
8.
J R Fike C E Cann T L Phillips M Bernstein P H Gutin K Turowski K A Weaver R L Davis R J Higgins V DaSilva 《Neurosurgery》1985,16(4):530-537
The canine brain is a good model of the human brain for studying radiation damage after megavoltage x-irradiation for brain tumors. We have further developed this model to study radiation damage induced by high activity interstitial 125I sources. Removable 125I sources were implanted in normal canine brains, and doses of 1,000 to 10,000 rads were delivered to a reference point at a 10-mm radius from the source; dose rates were 35 to 40 rads/hour at the reference point. Serial quantitative analysis of tissue damage (tissue density and contrast enhancement) was done using computed tomographic scanning up to 6 months after implantation and was compared to histopathological findings after the animals were killed. At doses greater than 19,000 rads (i.e., inside the reference point), frank coagulation necrosis was observed. Pronounced vessel-related changes, manifest as areas of contrast enhancement, corresponded to tissues receiving a minimum of 6,000 rads and a maximum of 19,000 rads. These results indicate that this model can be used in serial noninvasive studies to quantify the development of damage induced by interstitial irradiation and to provide dose-response information in individual animals. 相似文献
9.
Increased neurogenesis after cerebral ischemia suggests that functional recovery after stroke may be attributed, in part, to neural regeneration. In this study, we investigated the role of neurogenesis in the behavioral performance of gerbils after cerebral global ischemia. We used ionizing radiation to decrease neural regeneration, and 2 weeks later cerebral global ischemia was induced by bilateral common carotid artery occlusion. One month after the occlusion, the animals were behaviorally tested. Irradiation alone reduced neurogenesis but did not change vascular or dendritic morphology at the time of behavioral testing. Neither did irradiation, ischemia, or combined treatment impair rotor-rod performance or alter open-field activity. Gerbils subjected to both irradiation and ischemia demonstrated impaired performance in the water-maze task, compared with those that received only ischemia, radiation, or no treatment. These impairments after cerebral global ischemia under conditions of reduced neurogenesis support a role for the production of new cells in mediating functional recovery. 相似文献
10.
Measurement of regional cerebral blood flow using ultrafast computed tomography. Theoretical aspects 总被引:3,自引:0,他引:3
Theoretical and practical limitations have prevented the measurement of regional cerebral blood flow using dynamic x-ray computed tomography. Development of the ultrafast computed tomography scanner has made it possible to overcome the practical limitations and measure changes in contrast concentration in the brain with excellent time and spatial resolution. By applying modifications of indicator dilution theory, we have derived a method to use these changes in contrast concentration determined using ultrafast computed tomography to measure the fractional vascular volume, mean transit time of blood, and blood flow within specific regions of the brain in a relatively simple and practical manner. This method could theoretically be used in the evaluation of physiological and pathophysiological alterations in cerebral blood flow. 相似文献