Reactivation Of Strain Research Articles

Linking cerebral metabolic function to stress vulnerability (Commentary on Knapman et al.)

Stress is linked to a wide variety of psychological and somatic ailments, including affective diseases (such as depression) and post-traumatic stress disorder. In recent years it has become increasingly clear that the impact of stress on pathology varies substantially from individual to individual (McEwen & Stellar, 1993; Radley et al., 2011). Defining mechanisms underlying individual differences is crucial to understanding the biological basis of stress control and using this knowledge to develop treatment strategies for stress-related diseases. This issue of European Journal of Neuroscience, Knapman et al. (2012) use state-of-the-art imaging methods and proteomics to explore neural events associated with differential stress reactivity in strains of mice selected for low, intermediate and high stress reactivity, as defined by the magnitude of corticosteroid responses to acute stressors. The strain with the greatest corticosterone reactivity to stress has memory deficits that are accompanied by lateralized reductions in hippocampal N-acetyl aspartate (NAA), reduced basal activity in the hippocampus and alterations in expression of hippocampal proteins regulating cellular energy metabolism. The data indicate a novel connection between susceptibility to stress and hippocampal (and perhaps cortical) metabolic function, suggesting mitochondrial dysfunction as a possible mechanism for stress vulnerability and, by extension, stressrelated disease processes. It is generally recognized that animal models of psychiatric disorders are problematic. The (always limited) validity of a model will depend on how well it matches the human disorder. For psychiatric disorders, features related to brain structure, metabolism and function will obviously be of primary relevance and interest. Beyond the implications for individual differences, this work demonstrates the power of advanced magnetic resonance techniques to probe in vivo metabolism and neuronal activity. NAA is now generally accepted as a relatively non-specific marker of neuronal integrity and mitochondrial metabolism (de Graaf, 2007). The value of magnetic resonance spectroscopy (MRS) lies in its ability to measure NAA (and several other major metabolites not probed in the present work) non-invasively and longitudinally in brain in both humans and animal models under a variety of parallel diagnostic criteria and treatment conditions. Longitudinal measures are of particular relevance for mechanistic approaches in animals, where one can achieve ‘before and after’ measurements associated with experimental interventions or genetic manipulations. Moreover, metabolic and functional measures may become clinically relevant at the early stages of a neurochemical disorder, before volume changes in the brain are apparent. Beyond MRS, manganese-enhanced magnetic resonance imaging, although not likely to be applicable to human studies, is becoming a useful adjunct to anatomical magnetic resonance imaging (Inoue et al., 2011) that can provide a crude but unique measure of the functional status of neuronal pathways. Studies like that of Knapman et al. (2012) can bridge the gap between detailed biochemical ⁄ proteomic analysis in animal models and dynamic functional ⁄metabolic measures in the human brain.

Effect of exercise training on vascular reactivity in inbred strains of mice

The aim of this study was to characterize the strain‐dependent differences in vascular reactivity in aorta from sedentary and exercise‐trained mice. Male mice (n ≈ 8/strain) from 5 inbred strains (129S1, 129X1, C57BL/6J, FVB, PWD) were assigned to either sedentary or exercise training (EX) groups. EX mice completed a 4‐wk treadmill running protocol (5 days/wk, 60 min/day, 60% of max speed). After training, aortic rings were suspended for isometric tension recording. Exercise training had no effect on vascular reactivity in any strain. Significant strain effects were found for maximal responses to phenylephrine (PE) and potassium chloride (KCl). For each agent, aorta from PWD had the lowest (PE = 5.4 ± 2.0 mN, KCl = 12.0 ± 2.6 mN) and aortas from 129‐substrains had the highest (PE = 16.4 ± 3.5 mN, KCl = 17.9 ± 3.3 mN) responses. Relaxation responses to acetylcholine were also different across strains, with aortas from the 129‐substrains having the lowest (73.0 ± 16.8%) and aorta from the FVB having the highest (90.6 ± 12.6%) responses. Relaxation responses to sodium nitroprusside were not different across strains. Strain‐dependent differences in sensitivity were observed for all agents tested. The large difference in maximal responses and sensitivity to vascular agents across mouse strains suggests that genetic background significantly affects vascular responsiveness.Supported by NIH grant HL085918 to MPM

Ocular reactivation phenotype of HSV-1 strain F(MP)E, a corticosteroid-sensitive strain

Purpose. Elucidate the ocular reactivation of HSV-1 strain F(MP)E. Methods. Rabbit corneas were infected with HSV-1 strains McKrae and F(MP)E. Latency was established and rabbits were treated with epinephrine iontophoresis or corticosteroid injection (immunosuppression). Cultured tear films were used to determine the presence of infectious virus. Eyes of immunosuppressed rabbits were also examined by slit lamp biomicroscopy. Trigeminal ganglia were co-cultured on indicator cells at time of sacrifice for detection of virus. Quantitative real-time PCR was used to detect the number of viral genome copies in the trigeminal ganglia. Results. Acute infections by strains McKrae and F(MP)E were the same. Ocular reactivation of strain F(MP)E by epinephrine iontophoresis was significantly reduced compared to McKrae (P = 0.0001), but was not significantly different from McKrae after corticosteroid injection (P > 0.29). Slit lamp examination following corticosteroid injection showed a correlation of recurrent herpetic lesions with infectious virus in tear film swabs for both McKrae and F(MP)E. Trigeminal ganglia from rabbits latently infected with each strain and each method of induced reactivation resulted in infectious virus (P = 0.69). Genome copies for both strains were present and were highly variable. Conclusions. HSV-1 strain F(MP)E has low reactivation following epinephrine iontophoresis compared to McKrae, but has high reactivation like McKrae in response to corticosteroids. The difference in reactivation following epinephrine iontophoresis is not due to a difference in the establishment of latency.

Cellular and humoral factors in host susceptibility to Lewis lung carcinoma.

Cellular and humoral anti-tumour reactivity in strains of mice highly susceptible (C57Bl/6) or less susceptible (C57Cl/6 x DBA/2 = B6D2F1) to Lewis lung carcinoma (LLC) was investigated. Natural killer cell activity in a 51Cr release assay against this tumour could be demonstrated with a good correlation to in vivo susceptibility. This has not been demonstrated earlier for solid, spontaneous tumours. T-cell deficiency (congenital athymic (nude mice)) did not affect the cumulative incidence of tumour take. However, the number of lung metastases was significantly reduced in nude mice. Treatment with antilymphocyte serum (ALS) increased the susceptibility to LLC in both strains. In a soft agar colony assay a marked reduction in the number of colonies was observed when tumour cells were incubated with serum from B6D2F1 mice as compared to serum from C57Bl/6 mice, prior to seeding. Apparently naturally occurring cellular, as well as humoral effector mechanisms are involved in host resistance to Lewis lung carcinoma in the mouse.

Human transfer factor activity in the guinea pig: Absence of antigen specificity

Human transfer factor of known antigen specificity was used to induce skin-test reactivity in strain 13 guinea pigs. This reactivity is reproducible, is dependent upon preexposure of the animal to subsensitizing doses of antigen, persists for at least 14 weeks, and is reflected in some cases by antigen-induced lymphocyte transformation. The skin test response in guinea pigs does not reflect the antigen reactivities of the human TF donor; this suggests that in guinea pigs the TF may augment a low level of sensitization produced during the priming step.

Memory and Transfer of Information

Memory and Transfer of Information