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ABSTRACT: Mesoangioblasts are vessel-derived stem cells that differentiate into mesodermal derivatives. We have isolated postnatal aorta-derived mesoangioblasts (ADMs) that differentiate into smooth, skeletal, and cardiac muscle, and adipocytes, and regenerate damaged skeletal muscle in a murine model for Duchenne muscular dystrophy. We report that the marker profile of ADM is similar to that of mesoangioblasts isolated from embryonic dorsal aorta, postnatal bone marrow, and heart, but distinct from mesoangioblasts derived from skeletal muscle. We also demonstrate that ADM differentiate into myelinating glial cells. ADM localize to peripheral nerve bundles in regenerating muscles and exhibit morphology and marker expression of mature Schwann cells, and myelinate axons. In vitro, ADM spontaneously express markers of oligodendrocyte progenitors, including the chondroitin sulphate proteoglycan NG2, nestin, platelet-derived growth factor (PDGF) receptor α, the A2B5 antigen, thyroid hormone nuclear receptor α, and O4. Pharmacological inhibition of Rho kinase (ROCK) initiated process extension by ADM, and when combined with insulin-like growth factor 1, PDGF, and thyroid hormone, enhanced ADM expression of oligodendrocyte precursor markers and maturation into the oligodendrocyte lineage. ADM injected into the right lateral ventricle of the brain migrate to the corpus callosum, and cerebellar white matter, where they express components of myelin. Because ADM differentiate or mature into cell types of both mesodermal and ectodermal origin, they may be useful for treatment of a variety of degenerative diseases, or repair and regeneration of multiple cell types in severely damaged tissue.
Stem cells and development 07/2011; 21(7):1069-89. · 4.15 Impact Factor
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12/2010; , ISBN: 9780470650714
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ABSTRACT: It has been shown that dendritic branching in neural cardiorespiratory and locomotor centers can be attenuated with exercise training (ET) initiated immediately after weaning. The purpose of this study was to determine whether neuroplastic changes occur within cardiorespiratory and locomotor centers due to ET after maturation. Male Sprague-Dawley rats (21 days old, n=28) were individually housed in standard cages. At 91 days of age, animals were divided into two groups: untrained (UN; n=14) and trained (TR; n=14). The TR group exercised spontaneously for 50 days on running wheels. ET indexes were obtained, including maximal O2 consumption, percent body fat, resting heart rate, and heart weight-to-body weight ratios. The brain was processed with a modified Golgi-Cox procedure. Impregnated neurons from the periaqueductal gray (PAG), posterior hypothalamic area (PH), nucleus of the tractus solitarius (NTS), cuneiform nucleus (CnF), rostral ventrolateral medulla, nucleus cuneatus, and cerebral cortex were examined. Neurons were traced and analyzed using the Sholl concentric ring analysis of dendritic branching. The mean total number of dendritic intersections with the concentric rings per neuron per animal were compared between UN and TR groups. There were significant differences between UN and TR groups in the PH, PAG, CnF, and NTS in the total number of intersections per animal. In some areas, the effect size was smaller when ET was initiated in mature animals, possibly related to their relatively reduced activity levels. In conclusion, the adult rat brain remains dynamic and adapts to chronic ET. However, some brain areas appear to be more affected if ET is initiated in early postnatal development.
Journal of Applied Physiology 03/2010; 108(6):1582-90. · 3.75 Impact Factor
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Gary A Iwamoto
Frontiers in physiology. 01/2010; 1:142.
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ABSTRACT: African American men have stiffer large central arteries and impaired dilation of smaller peripheral arteries when compared to their white peers. The purpose of this study was to examine the effect of resistance exercise training (RT) on vascular function and central blood pressure (BP) in young (22 years) African American and white men.
Vascular and hemodynamic measures were made in 19 African American and 18 white men at baseline and following 6-weeks of RT. Carotid BP and carotid/brachial artery beta-stiffness were measured by tonometry and ultrasonography, respectively. Aortic BP was measured by radial artery tonometry and a generalized transfer function. Aortic stiffness was measured by pulse wave velocity (PWV). Forearm blood flow (FBF) was measured by strain-gauge plethysmography before and during reactive hyperemia (RH) induced by 5-min of brachial artery occlusion.
There were similar reductions in central BP and similar increases in FBF-RH in both African American and white men following RT (p<0.05). There were no changes in brachial systolic BP, carotid stiffness, and aortic PWV in either group (p>0.05). There was an increase in brachial stiffness in African American but not white men following RT (p<0.05).
RT led to reductions in central BP and increases in microvascular endothelial function with no effect on central artery stiffness in both groups of young men. RT increased brachial stiffness in African American men. Measurement of conventional brachial BP does not capture the central hemodynamic and vascular response to exercise training due to disparate racial changes in regional vascular properties.
Atherosclerosis 05/2009; 207(1):220-6. · 3.79 Impact Factor
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ABSTRACT: African Americans have a greater prevalence of hypertension and diabetes compared with white Americans, and both autonomic dysregulation and inflammation have been implicated in the etiology of these disease states. The purpose of this study was to examine the cardiac autonomic and systemic inflammatory response to resistance training in young African-American and white men. Linear (time and frequency domain) and nonlinear (sample entropy) heart rate variability, baroreflex sensitivity, tonic and reflex vagal activity, and postexercise heart rate recovery were used to assess cardiac vagal modulation. C-reactive protein (CRP) and white blood cell count were used as inflammatory markers. Twenty two white and 19 African-American men completed 6 wk of resistance training followed by 4 wk of exercise detraining (Post 2). Sample entropy, tonic and reflex vagal activity, and heart rate recovery were increased in white and African-American men following resistance training (P < 0.05). Following detraining (Post 2), sample entropy, tonic and reflex vagal activity, and heart rate recovery returned to baseline values in white men but remained above baseline in African-American men. While there were no changes in white blood cell count or CRP in white men, these inflammatory markers decreased in African-American men following resistance training, with reductions being maintained following detraining (P < 0.05). In conclusion, resistance training improves cardiac autonomic function and reduces inflammation in African-American men, and these adaptations remained after the cessation of training. Resistance training may be an important lifestyle modification for improving cardiac autonomic health and reducing inflammation in young African-American men.
AJP Regulatory Integrative and Comparative Physiology 02/2009; 296(4):R1098-105. · 3.34 Impact Factor
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Journal of Applied Physiology 09/2008; 105(2):773. · 3.75 Impact Factor
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ABSTRACT: Analgesic balms (AB) are widely used in sports medicine. We previously have examined effects of various counterirritant-based AB on pressor responses evoked by muscular contraction (MC), mediated by group III and IV muscle afferents known to produce exercise and nociceptive responses. Our purpose was to examine trolamine salicylate-based analgesic balm (TS) effects.
Ten healthy, adult male and female cats were used. Decerebration under halothane allowed elimination of anesthesia. Electrical stimulation of L7 and S1 ventral roots evoked static MC (30 s). After control runs, commercial TS (10% concentration) was applied to the skin over the contracting muscles of one hind limb (N = 5). MC was evoked every 10 min, alternating between sides. Ipsilateral (T = 0, T + 20, T + 40, T + 60 min) and contralateral (T - 10, T + 10, T + 30, T + 50 min) responses were analyzed. Five additional cats received AB minus TS.
There were significant attenuations in both peak mean arterial pressure (MAP), in the last 12 s and the last 6 s of the 30 s of MC for both contra- and ipsilateral limbs occurring at T + 50 and T + 60 min after TS application, respectively. No significant changes in heart rate (HR) responses were seen for either the ipsi- or contralateral stimulation. There were no changes in MAP or HR in control cats.
These results indicate that TS affects the end of the 30 s of MC, which is thought to be mainly chemically mediated through group IV afferents. TS represents the salicylate class of AB and has no counterirritant properties. TS works as an inhibitor of cyclooxygenase (prostaglandin formation) and is, at least in part, blood borne.
Medicine & Science in Sports & Exercise 12/2007; 39(11):1942-8. · 4.43 Impact Factor
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ABSTRACT: Thyroid hormones play an important role in brain development. In the present study, we examined the influence of transient postnatal hypothyroidism on reproductive neuroendocrine and behavioral outcomes in the male Syrian (golden) hamster. Hamster pups were rendered hypothyroid following exposure to the goitrogen, 6-n-propyl-2-thiouracil (PTU), between postnatal (PN) day 0 (birth) and PN25 (weaning). By 15 days after cessation of PTU, exposure (PN40) serum thyroxine levels had returned to control levels. The testes of treated males were approximately 30% heavier than controls and daily sperm production was increased by 73%. Immunocytochemistry for GnRH revealed that the total number of GnRH neurons did not vary between groups; however, a shift in the distribution of GnRH neurons was observed in treated males such that more GnRH immunoreactive neurons were found in the caudal portion of their normal distribution. The shift in GnRH distribution was associated with a significant reduction (40-50%) in pituitary gonadotropin secretion. Behaviorally, treated males took significantly longer to investigate the anogenital region and then mount a receptive female. A corresponding reduction in the total number of anogenital investigations and mounts was observed. This difference between treated males and controls was reduced, but not eliminated, over successive trials and by the third trial the number of intromission was similar between treated and control males. We conclude that the full complement of adult reproductive functions observed in the male golden hamster requires thyroid hormones during the early postnatal period. The severity of the effects induced by early hypothyroidism in this species varies from transient to permanent, depending on the endpoint.
Physiology & Behavior 05/2007; 90(5):771-81. · 2.87 Impact Factor
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ABSTRACT: It has been shown previously that dendritic branching in cardiorespiratory and locomotor brain areas can be attenuated with exercise training (ET). It was not known whether this process was reversible. Twenty-three (n = 23) male Sprague-Dawley rats were individually caged and divided into two groups: untrained (UN; n = 11) and detrained (DTR; n = 12). DTR were provided with a running wheel at 21 days of age and exercised spontaneously. After 120 days (70 days of ET followed by 50 days of detraining), ET indexes were obtained, including maximal oxygen uptake, percent body fat, resting heart rate, and heart weight-to-body weight ratios. The brain was processed according to a modified Golgi-Cox procedure. Impregnated neurons from the periaqueductal gray (PAG), posterior hypothalamic area (PH), nucleus of the tractus solitarius (NTS), and cuneiform nucleus (CfN) were examined in coronal sections. Neurons were traced using a camera lucida technique and analyzed using the Sholl concentric ring analysis of dendritic branching. t-Tests compared the mean number of intersections per neuron by grouping inner rings, outer rings, and total number of intersections per animal. There were no significant differences between UN and DTR in PH, PAG, CfN, and NTS in the inner rings, outer rings, and total number of intersections per animal. A separate group of animals was used to show that a training effect in the CfN and NTS was present at 56 days of ET. Our results show that dendritic attenuation resulting from 70 days of ET in PH, PAG, CfN, and NTS is completely reversed with 50 days of detraining.
Journal of Applied Physiology 11/2006; 101(4):1243-51. · 3.75 Impact Factor
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Journal of Applied Physiology 04/2006; 100(3):1077-9. · 3.75 Impact Factor
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ABSTRACT: Neuronal activity has been shown to be attenuated in cardiorespiratory and locomotor centers of the brain in response to a single bout of exercise in trained (TR) vs. untrained (UN) animals, but the mechanisms remain obscure. Based on this finding, dendritic branching patterns of seven brain areas associated with cardiorespiratory and locomotor activity were examined in TR and UN animals. Twenty-eight male Sprague-Dawley rats were kept in individual cages and divided into TR and UN. TR were provided with a running wheel and exercised spontaneously. After 85 or 120 days, exercise training indexes were obtained, including maximal oxygen consumption, percent body fat, resting heart rate, and heart weight-to-body weight ratios. The brain was removed and processed according to a modified Golgi-Cox procedure. Impregnated neurons from seven brain areas were examined in coronal sections: the periaqueductal gray, posterior hypothalamic area, nucleus of the tractus solitarius, rostral ventrolateral medulla, cuneiform nucleus, nucleus cuneatus, and cerebral cortex. Neurons were traced using a camera lucida technique and analyzed using the Sholl analysis of dendritic branching. t-tests were conducted to compare the mean number of intersections per neuron by grouping inner rings and outer rings and also comparing the total number of intersections per animal. There were significant differences between groups in the posterior hypothalamic area, periaqueductal gray, cuneiform nucleus, and nucleus of the tractus solitarius in the inner rings, outer rings, and the total number of intersections per animal. Our results show that dendritic fields of neurons in important cardiorespiratory and locomotor centers of the brain are attenuated in TR animals.
Journal of Applied Physiology 01/2006; 99(6):2312-22. · 3.75 Impact Factor
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ABSTRACT: Adipocyte hyperplasia is characteristic of some forms of human obesity, but the role of adipocyte number in obesity and how normal adipocyte number is established are unclear. Preadipocytes proliferate and then differentiate to become mitotically quiescent adipocytes. This involves exit from the cell cycle, a process regulated by cell cycle inhibitors such as the cyclin-dependent kinase inhibitors (CDKIs) p27 and p21. 3T3-L1 preadipocytes show marked changes in p27 and p21 during differentiation, suggesting CDKIs may regulate establishment of adipocyte number in vivo. To study the role of these CDKIs in adipogenesis, we analyzed adult p27 knockout (p27KO), p21 knockout (p21KO), p27/p21 double knockout (DBKO), and wild-type (WT) mice. Adult DBKO mice weighed 100% more and had fourfold increases in body fat percentage compared with WT. Fat pad weights were increased 80, 90, and 500% in p27KO, p21KO, and DBKO mice, respectively, compared with WT. Adipocyte numbers of p27KO, p21KO, and DBKO mice were 1.9-, 1.7-, and 6.1-fold, respectively, that of WT; adipocyte size was not increased. DBKO mice showed glucose intolerance, insulin insensitivity, hepatic steatosis and dyslipidemia; gradations of these effects occurred in p27KO and p21KO mice. In conclusion, p27KO and p21KO mice are obese because of adipocyte hyperplasia, and DBKO mice have further increases in obesity and adipocyte hyperplasia, indicating that their functions in establishing adipocyte number are not redundant. p27 and p21 are major regulators of adipocyte number in vivo, and knockouts lacking one or both of these proteins provide models for producing adipocyte hyperplasia and understanding its metabolic consequences.
The FASEB Journal 01/2005; 18(15):1925-7. · 5.71 Impact Factor
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ABSTRACT: To evaluate changes in heart rate (HR) and mean arterial pressure (MAP) as indicators of changes in pressor response for muscle afferents after topical application of menthol (MEN)-based analgesic balm.
11 decerebrate cats.
Pressor responses were reflexively evoked by static contraction of hind limb muscles, which are caused by group III and IV afferents. Responses were monitored without interference from anesthesia or effects of higher brain function by the use of decerebrate cats. After obtaining baseline data, MEN analgesic balm (1.9%) was applied to the skin over contracting muscles of 1 hind limb in 6 cats; petrolatum was applied to 5 control cats. Muscle contractions were evoked every 10 minutes, alternating between hind limbs, for 120 minutes. Peak MAP and HR were analyzed.
Peak MAP responses evoked by static muscle contraction for the ipsilateral hind limb were significantly attenuated 20 minutes after application, but approached baseline values 40 minutes after application. The pressor response was significantly decreased 20 minutes after application during the last 12 seconds of the stimulus, which was attributed to group IV afferents. There were no significant differences in HR responses.
Application of MEN analgesic balm to the skin over contracting muscles significantly decreased the pressor response to static muscle contractions. This suggests that topical application of MEN has effects on responses evoked from receptors located in muscles. The MEN analgesic balm appeared to attenuate the pressor response 20 minutes after application, but it was a short-term effect.
American Journal of Veterinary Research 10/2004; 65(9):1204-10. · 1.27 Impact Factor
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ABSTRACT: Insular cortex (IC) is recognized as a potential site for "central command" of cardiorespiratory responses during exercise. Muscular contraction (MC) decreased the discharge rate of most IC neurons. Activity of most contraction sensitive neurons was either not altered by elevating blood pressure or showed a response converse to that of MC. IC may thus have a role in central command but the area is clearly modulated by MC.
Brain Research 06/2004; 1008(2):273-7. · 2.73 Impact Factor
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ABSTRACT: Capsaicin-based analgesic balm decreases pressor responses evoked by muscle afferents. Physically active individuals use countless analgesic balm (AB) products with various active ingredients daily. Despite this, few studies have investigated the mechanism of action and efficacy of AB.
We examined the effects of capsaicin (CAP) application on pressor responses evoked by muscle contraction (MC), which are mediated by group III and IV muscle afferents.
Heart rate (HR), blood pressure, and end-tidal CO2 were monitored in cats (N = 12) decerebrated under halothane. Decerebration eliminated anesthesia use and effects from the higher brain. Electrical stimulation of L7 and S1 ventral roots evoked static hindlimb MC (30 s). After control runs, a commercial CAP (4.95% Oleoresin Capsicum) AB was applied to the skin over the contracting muscles of one hindlimb. MC were evoked every 10 min, alternating between hindlimbs. Data were analyzed with RM ANOVA and Tukey post hoc test.
Changes in peak mean arterial pressure (MAP) induced by static ipsilateral MC were significantly attenuated at 20 min and tended to approach baseline levels at 40 min after CAP application. The mean (+/- SEM) of the peak MAP for the ipsilateral side just before application (T = 0), at 20 min (T+20), and 40 min (T+40) were 28.3 mm Hg +/- 6.4, 13.8 mm Hg +/-2.9, and 22.6 mm Hg +/- 5.2, respectively. There were no significant changes in HR.
Cardiovascular effects due to activation of group III and IV afferent fibers were significantly attenuated by the application of CAP. The time course of the effects appeared to support the need for repeated CAP application for pain relief. Central nervous system circuitry responsible for this effect awaits elucidation.
Medicine & Science in Sports & Exercise 04/2004; 36(3):444-50. · 4.43 Impact Factor
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ABSTRACT: Pressor responses are reflexly evoked by the activation of groups III and IV muscle afferents, which are also known to mediate nociceptive responses. In this experiment, the effects of analgesic balm (AB) application on these responses were investigated without the interference of other types of anesthesia or effects from the higher brain.
Heart rate (HR), blood pressure, and end-tidal CO(2) were monitored in midcollicularly decerebrated cats. Static contractions (30 s) of hindlimb muscles were evoked by electric stimulation of L7 and S1 ventral roots. After control runs, a commercial AB (1% capsaicin, 12.5% methyl salicylate) was applied to the skin surface over the contracting muscles. Muscle contractions were evoked every 10 min, alternating between the two hindlimbs.
Changes in mean arterial pressure (MAP) evoked by static ipsilateral muscular contraction were significantly attenuated 20 min and 40 min after AB application. The decreases in the pressor response were significant at both the initial and the last parts of the stimulus intervention after 20 min of AB application. There were no significant changes in the response to contraction of the hindlimb contralateral to the AB application. Application of AB to the contralateral leg did not add to the ipsilateral effects.
AB application to the skin surface over contracting muscles significantly decreased autonomic responses to static muscular contraction. This effect was independent of higher cortical processing and strongly suggests that application of methyl salicylate and capsaicin on the skin has analgesic effects on signals from receptors located in muscle.
Medicine & Science in Sports & Exercise 10/2002; 34(9):1440-5. · 4.43 Impact Factor
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ABSTRACT: The purpose of this study was to determine whether exercise training changes the extent or pattern of activation of areas in the central nervous system (CNS) involved in cardiorespiratory control. Rats that spontaneously trained on running wheels for 80-100 days were compared to rats that were not provided an opportunity to exercise. Selected brain regions including the hypothalamic and mesencephalic locomotor regions, and ventrolateral medulla were studied using c-Fos-like immunocytochemistry. A single test bout of exercise evoked significantly less activation as indicated by Fos labeling in the posterior (caudal) hypothalamic area, periaqueductal gray, nucleus of the tractus solitarius and the rostral ventrolateral medulla of the trained rats when compared to sedentary rats. These results are consistent with the concept that the nervous system changes its responses to a given level of exercise after training. These changes may also be related to perceived exertion.
Brain Research 09/2002; 947(2):225-33. · 2.73 Impact Factor
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ABSTRACT: Pheromonal stimuli elicit rapid behavioral and reproductive endocrine changes in the ewe. The neural pathways responsible for these effects in sheep are unknown, in part, because the olfactory bulb projections have not been examined in this species. Using the anterograde and retrograde neuronal tracer, wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP), we describe the afferent and efferent olfactory bulb connections of the Suffolk ewe. Injections of WGA-HRP limited to the main olfactory bulb resulted in retrograde labeling of cells in numerous telencephalic, diencephalic, and metencephalic regions. Terminal labeling was limited to layer Ia of ipsilateral cortical structures extending rostrally from the anterior olfactory nucleus (AON), piriform cortex, anterior-, and posterolateral-cortical amygdaloid nuclei to lateral entorhinal cortex caudally. Injections involving the accessory olfactory bulb and AON produced additional labeling of cells within the bed nucleus of the stria terminalis (BNST), medial nucleus of the amygdala, and a few cells in the posteromedial cortical nucleus of the amygdala. Terminal labeling included a small dorsomedial quadrant of BNST and also extended to the far lateral portions of the supraoptic nucleus. A clearly defined accessory olfactory tract and nucleus was not evident, perhaps due to limitations in the sensitivity of the method. With this possible exception, the afferent and efferent olfactory connections in the sheep appear similar to those reported for other species.
Brain Research Bulletin 02/1998; · 2.82 Impact Factor
