Neuroplastic adaptations to exercise: neuronal remodeling in cardiorespiratory and locomotor areas.

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.     

Nitric oxide synthase (NOS) coexists with activated neurons by skeletal muscle contraction in the brainstem of cats

Contraction of skeletal muscle evokes increases in arterial blood pressure and heart rate. Some regions of the brainstem have been implicated for expression of the cardiovascular responses to muscle contraction. Previous studies have reported that static muscle contraction induced c-Fos protein in the nucleus of tractus solitarii (NTS), lateral reticular nucleus (LRN), lateral tegmental field (FTL), subretrofacial nucleus (SRF), A1 region and periaqueductal gray (PAG) of the brainstem. Furthermore, neuronal NADPH-diaphorase (NADPH-d), which is considered as a marker of neuronal nitric oxide synthase (nNOS), has been localized in those same regions. In this study, static muscle contraction was induced by electrical stimulation of the L7 and S1 ventral roots in anaesthetized cats. Distribution of c-Fos protein within neurons containing nNOS was evaluated by double labeling methods in order to determine if nNOS containing neurons in the brainstem were activated during muscle contraction. The results indicate that c-Fos protein colocalized with NADPH-d positive staining within the neurons of the SRF and PAG, but not within the NTS neurons. Distinct number of neurons with c-Fos protein was in close proximity to NADPH-d positive staining in the NTS, SRF, and PAG. Coexisting of c-Fos protein and NADPH-d positive staining was not observed in the LRN, FTL and A1 region. These findings demonstrate that nNOS containing neurons were activated by muscle contraction in the selective regions of the brainstem, and nNOS positive staining had close anatomic contacts with the neurons activated by contraction. This result provides neuroanatomic evidence suggesting that nitric oxide modulates the cardiovascular responses to muscle contraction within the NTS, SRF and PAG of the brainstem.     

Effects of CCK-8 on independent ingestion and central c-Fos-like immunoreactivity in rats on postnatal days 10 and 11

Controls of the independent ingestion of food in the preweanling rat emerge in the second postnatal week. We investigated the effects of CCK-8 (0, 1, 5, or 10 microg/kg IP) on intake and c-Fos-like immunoreactive (CFLI) cells in hindbrain and forebrain on postnatal days 10 and 11. Five micrograms per kilogram decreased intake and increased the number of CFLI cells in four subnuclei of the nucleus tractus solitarius (NTS), in arcuate nucleus (ARC), and in central nucleus of the amygdala (CeA). Ten micrograms per kilogram decreased intake and increased CFLI in three NTS subnuclei as much as 5 microg/kg did, but was more potent than 5 microg/kg in the medial NTS subnucleus. Ten micrograms per kilogram increased CFLI in paraventricular (PVN) and supraoptic (SON) nuclei, but 5 microg/kg did not. Thus, reduction of intake by CCK-8 on days 10 and 11 is associated with increased hindbrain and forebrain CFLI.     

Detraining produces minimal changes in physical performance and hormonal variables in recreationally strength-trained men

The object of this study was to examine changes in muscular strength, power, and resting hormonal concentrations during 6 weeks of detraining (DTR) in recreationally strength-trained men. Each subject was randomly assigned to either a DTR (n = 9) or resistance training (RT; n = 7) group after being matched for strength, body size, and training experience. Muscular strength and power testing, anthropometry, and blood sampling were performed before the experimental period (T1), after 3 weeks (T2), and after the 6-week experimental period (T3). One-repetition maximum (1RM) shoulder and bench press increased in RT at T3 (p 相似文献   

辣椒素引起脑干内心血管活动相关核团中c-fos的表达

在１６只切断两侧缓冲神经的大鼠,观察颈总动脉注射辣椒素对脑干内心血管活动相关核团ｃ－ｆｏｓ原癌基因表达的影响。在剂对照组大鼠脑干,仅见少数Ｆｏｓ蛋白样免疫反应（ＦＬＩ）神经元。与对照组相比,颈总动脉注射辣椒素（１０μｍｏｌ,０．１ｍｌ）时,脑干内巨细胞旁外侧核（ＰＧＬ）、蓝斑（ＬＣ）、最后区（ＡＰ）和孤束核（ＮＴＳ）等部位的ＦＬＩ神经元显著增加,而中脑中央灰质（ＰＡＧ）和中缝核群（ＲＮ）的ＦＬＩ神     

Excitatory convergence of periaqueductal gray and somatic afferents in the solitary tract nucleus: role for neurokinin 1 receptors

Our previous studies (Boscan P, Kasparov S, and Paton JF. Eur J Neurosci 16: 907-920, 2002) showed that activation of somatic afferents attenuated the baroreceptor reflex via neurokinin type 1 (NK(1)) and GABA(A) receptors within the nucleus of the solitary tract (NTS). The periaqueductal gray matter (PAG) can also depress baroreceptor reflex function and project to the NTS. In the present study, we have tested the possibility that the dorsolateral (dl)-PAG projects to the NTS neurons that also respond to somatic afferent input. In an in situ, arterially perfused, unanesthetized decerebrate rat preparation, somatic afferents (brachial plexus), cervical spinal cord, and dl-PAG were stimulated electrically, whereas NTS neurons were recorded extracellularly. From 45 NTS neurons excited by either brachial plexus or dl-PAG stimulation, 41 received convergence excitatory inputs from both afferents. Onset latency and evoked peak discharge frequency from brachial plexus afferents were 39.4 +/- 4.7 ms and 10.7 +/- 1.1 Hz, whereas this was 43.9 +/- 6.4 ms and 7.9 +/- 1 Hz, respectively, following dl-PAG stimulation. As revealed by using a paired pulse stimulation protocol, monosynaptic connections were found in 9 of 36 neurons tested from both spinal cord and dl-PAG. We tested NK(1)-receptor sensitivity in 38 neurons that received convergent inputs from brachial plexus/PAG. Fifteen neurons were sensitive to selective antagonism of NK(1) receptors. CP-99994, the NK(1) antagonist, failed to alter ongoing firing activity but reduced the evoked peak discharge frequency following stimulation of both brachial plexus (from 12.3 +/- 1.8 to 7.2 +/- 1.3 Hz; P < 0.01) and PAG (from 7.8 +/- 1.5 to 4.5 +/- 1 Hz; P < 0.01). We conclude that 1) somatic brachial and PAG afferents can converge onto single NTS neurons; 2) this convergence occurs via either direct or indirect pathways; and 3) NK(1) receptors are activated by some of these inputs.     

Mathematical modelling of neuronal dendritic branching patterns in two dimensions: application to retinal ganglion cells in the cat and rat

Sholl’s analysis has been used for about 50years to study neuron branching characteristics based on a linear, semi-log or log—log method. Using the linear two- dimensional Sholl’s method, we call attention to a relationship between the number of intersections of neuronal dendrites with a circle and the numbers of branching points and terminal tips encompassed by the circle, with respect to the circle radius. For that purpose, we present a mathematical model, which incorporates a supposition that the number of dendritic intersections with a circle can be resolved into two components: the number of branching points and the number of terminal tips within the annulus of two adjoining circles. The numbers of intersections and last two sets of data are also presented as cumulative frequency plots and analysed using a logistic model (Boltzmann’s function). Such approaches give rise to several new morphometric parameters, such as, the critical, maximal and mean values of the numbers of intersections, branching points and terminal tips, as well as the abscissas of the inflection points of the corresponding sigmoid plots, with respect to the radius. We discuss these parameters as an additional tool for further morphological classification schemes of vertebrate retinal ganglion cells. To test the models, we apply them first to three groups of morphologically different cat’s retinal ganglion cells (the alpha, gamma and epsilon cells). After that, in order to quantitatively support the classification of the rat’s alpha cells into the inner and outer cells, we apply our models to two subgroups of these cells grouped according to their stratification levels in the inner plexiform layer. We show that differences between most of our parameters calculated for these subgroups are statistically significant. We believe that these models have the potential to aid in the classification of biological images.     

颈动脉注射辣椒素对脑干心血管相关核团一氧化氮合酶和Fos表达的影响

实验采用NADPH－d组化技术和Fos蛋白免疫组化技术相结合的方法,观察了颈动脉注射辣椒不时,大鼠脑干心血管相关核团内NOS和Fos蛋白的分布以及两者的共存关系。结果显示：（1）颈动脉注射辣椒不可诱发脑干中最后区（AP）、孤束核（NTS）、巨细胞旁外侧核（PGL）和蓝斑（LC）等多个部位Fos样免疫反应（FLI)神经元显著增加 中脑中央灰质（PAG）和中缝核群（RN）的FLI神经元无明显改变。（2）PGL和NTS内NO合成神经元以及PGL内双标神经元数量也明显增加,而AG和RN中NO合成神经元无明显变化,在LC和AP仅偶见或未见NO合成神经元。（3）预先应用辣椒素受体阻断剂钌红或NMDA受体阻断剂MK－801,则明显减弱辣椒素的上述效应,以上结果表明,颈动脉注射辣椒素可兴奋脑干心血管活动相关核团神经元,NO在脑干核团对辣椒素的反应中发挥间接的调制作用,辣椒素的效应由香草酸受体（辣椒素受体）介导并有谷氨酸参与。     

Endothelin receptor antagonists reduce the pressor effects of angiotensin II into the periaqueductal gray area of rats.

Injection of ANGII (0.01, 0.1 and 1 nmol/rat) into the periaqueductal gray (PAG) area significantly (P<0.01) increased, in a dose-dependent manner, the mean arterial blood pressure (MAP). The increases in blood pressure induced by ANGII (1 nmol; 37 +/- 4 mmHg, n=5) were greatly reduced (>85%) by pre-administration of the ET(A) receptor antagonist FR139317 (5 nmol/rat) to the PAG area, but were unaffected by the ET(B) receptor antagonist BQ-788 (5 nmol/rat). SB209670, non-selective ET(A)/ET(B) receptor antagonist, also reduced the effect induced by ANGII. These results suggest that endogenous endothelin-1, via an action on ET(A) receptors, may contribute to the pressor effects of ANGII within the PAG area of rats.     

Identification of neural circuits involved in female genital responses in the rat: a dual virus and anterograde tracing study

The spinal and peripheral innervation of the clitoris and vagina are fairly well understood. However, little is known regarding supraspinal control of these pelvic structures. The multisynaptic tracer pseudorabies virus (PRV) was used to map the brain neurons that innervate the clitoris and vagina. To delineate forebrain input on PRV-labeled cells, the anterograde tracer biotinylated dextran amine was injected in the medial preoptic area (MPO), ventromedial nucleus of the hypothalamus (VMN), or the midbrain periaqueductal gray (PAG) 10 days before viral injections. These brain regions have been intimately linked to various aspects of female reproductive behavior. After viral injections (4 days) in the vagina and clitoris, PRV-labeled cells were observed in the paraventricular nucleus (PVN), Barrington's nucleus, the A5 region, and the nucleus paragigantocellularis (nPGi). At 5 days postviral administration, additional PRV-labeled cells were observed within the preoptic region, VMN, PAG, and lateral hypothalamus. Anterograde labeling from the MPO terminated among PRV-positive cells primarily within the dorsal PVN of the hypothalamus, ventrolateral VMN (VMNvl), caudal PAG, and nPGi. Anterograde labeling from the VMN terminated among PRV-positive cells in the MPO and lateral/ventrolateral PAG. Anterograde labeling from the PAG terminated among PRV-positive cells in the PVN, ventral hypothalamus, and nPGi. Transynaptically labeled cells in the lateral hypothalamus, Barrington's nucleus, and ventromedial medulla received innervation from all three sources. These studies, together, identify several central nervous system (CNS) sites participating in the neural control of female sexual responses. They also provide the first data demonstrating a link between the MPO, VMNvl, and PAG and CNS regions innervating the clitoris and vagina, providing support that these areas play a major role in female genital responses.     

5-羟色胺和一氧化氮合酶在大鼠中脑导水管周围灰质 和中缝核簇神经元内的共存

实验采用 NADPH组织化学和 5 - HT免疫组织化学双重显色方法研究了 5 - HT和一氧化氮合酶在大鼠中脑导水管周围灰质 (PAG)和中缝核簇神经元的分布特征及共存情况。结果表明 ;(1 )在 PAG腹外侧区中观察到大量的 NOS阳性神经元和 5 - HT样免疫阳性神经元 ,但是 NOS/ 5 - HT双标神经元较少 ,仅占该区 5 - HT样免疫阳性神经元 2 0 .1 % ,并且主要分布在该区的内侧部 ;在 PAG的背外侧区中观察到密集的 NOS阳性神经元 ,但是几乎未见 5 - HT免疫阳性神经元分布。(2 )在中缝核簇的大多数亚核内均可观察到大量的 NOS神经元和 5 - HT免疫阳性神经元。在中缝背核的内侧部、中缝背核的尾侧部、中缝正中核、尾侧线形核、中缝大核和中缝隐核内双标神经元分别占所在部位中 5 - HT免疫阳性神经元的 44 .6 %、5 3.4%、 44 .4%、 2 6 .2 %、 2 6 .7%和 2 1 .8%。然而在中缝苍白核内仅偶见少数双标神经元。研究结果表明 ,在 PAG和中缝核簇的一些神经元内 5 - HT可以与 NOS共存 ,提示这两种神经活性物质在功能上可能存在着某种相关性 ,有关这些双标神经元的功能意义尚需进一步研究。     

Circulating endothelin influences area postrema neurons

The recently described endothelium-derived constricting factor endothelin (ET) is a 21 amino acid peptide which is the most potent endogenous vasoconstrictor yet described. Binding sites for this peptide have been demonstrated within the circumventricular structures of the brain. One of these structures, the area postrema (AP), has been implicated in central cardiovascular control mechanisms. We have recently demonstrated that microinjection of ET into this structure results in dose-dependent changes in mean arterial blood pressure. The present studies were undertaken to test the hypothesis that ET elicits these effects as a result of influences on the activity of AP neurons. Using extracellular single unit recording techniques we have examined the effects of systemic administration of ET on the activity of AP neurons. A total of 60 AP neurons were tested for effects of ET (0.1-10.0 pmol) of which the spontaneous activity of 32 showed rapid (modified frequency of action potentials in the 60s following ET), reversible (return to baseline activity within 10 m) responses to this peptide. The initial response of the majority (84%) of AP neurons influenced by ET was excitatory, while a smaller proportion of AP neurons were inhibited (16%) by systemic administration of this peptide. We have also examined whether such excitatory effects were specific to AP neurons by comparing the above response characteristics to those observed in neurons in the adjacent commissural NTS. Such recordings demonstrated predominantly inhibitory (84% of influenced cells) responses of this group of NTS neurons to ET. While these findings demonstrate specific excitatory effects of systemic ET on the activity of AP neurons they also suggest a potential role for this peptide in controlling the activity of NTS neurons. These studies provide evidence that circulating ET influences AP neuronal function, although they offer no definitive information as to the specific site of action.     

Glycinergic transmission regulates dendrite size in organotypic culture

We previously demonstrated that inhibitory synaptic transmission influences dendrite development in vivo. We now report an analogous finding in an organotypic culture of a glycinergic projection nucleus, the medial nucleus of the trapezoid body (MNTB), and its postsynaptic target, the lateral superior olive (LSO) of gerbils. Cultures were generated at 6–7 days postnatal and grown in serum containing medium with or without the glycine receptor antagonist, strychnine (SN), at 2 μM. LSO neurons were then labeled with biocytin, and the dendritic arbors were analyzed morphometrically. Compared to neurons from age-matched in vivo tissue, the neurons cultured in control media were somewhat atrophic, including decreases in dendritic branching and length. Incubation in strychnine led to a dramatic increase in dendritic branching and total dendritic length. Control neurons averaged 6.3 branches, compared to 18 branches/neuron in SN-treated cultures. There was a similar increase in primary dendrites and total dendritic length. The physical elimination of MNTB cells did not mimic SN treatment, presumably because glycinergic LSO neurons generated intrinsic connections. In fact, the LSO soma area was significantly greater following MNTB removal, suggesting that these afferents provide a second signal to postsynaptic neurons. These results suggest that spontaneous glycinergic transmission regulates the growth of postsynaptic processes. © 1996 John Wiley & Sons, Inc.     

Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito

Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6–7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation) was performed 1–2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92–86% suppression of food intake at 2–24 h post-surgery compared with control group (no surgery). RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration) and satiety (meal interval) and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition. RKT improves food consumption post-surgically that may involve modulation of pain pathway.     

Detraining in the older adult: effects of prior training intensity on strength retention

In this study, we assessed the influence of training intensity on strength retention and loss incurred during detraining in older adults. In a previous study, untrained seniors (age = 71.0 +/- 5.0; n = 61) were randomly divided into 3 exercise groups and 1 control group. Exercise groups trained 2 days per week for 18 weeks with equivalent volumes and acute program variables but intensities of 2 x 15 repetitions maximum (RM), 3 x 9RM, or 4 x 6RM. Thirty of the original training subjects (age 71.5 +/- 5.2 years) participated in a 20-week detraining period. A 1RM for 8 exercises was obtained pre- and posttraining and at 6 and 20 weeks of detraining. The total of 1RM for the 8 exercises served as the dependent variable. Analysis of variance procedures demonstrated significant increases in strength with training (44-51%; p < 0.05), but no group effect. All training groups demonstrated significant strength decreases at both 6 and 20 weeks of detraining independent of prior training intensity (all group average 4.5% at 6 weeks and 13.5% at 20 weeks; p < 0.04). However, total-body strength was significantly greater than pretraining values after the detraining period (all group average 82% at 6 weeks and 49% at 20 weeks; p < 0.001). The results suggest that when older adults participate in progressive resistance exercise for 18 weeks, then stop resistance training (i.e., detrain), strength losses occur at both 6 and 20 weeks of detraining independent of prior resistance training intensity. However, despite the strength losses, significant levels of strength are retained even after 20 weeks of detraining. The results have important implications for resistance-trained older adults who could undergo planned or unplanned training interruptions of up to 5 months.     

Golgi-type I and Golgi-type II Neurons in the Ventral Anterior Thalamic Nucleus of the Adult Human: Morphological Features and Quantitative Analysis

The morphological and quantitative features of neurons in the adult human ventral anterior thalamic nucleus were studied in Golgi preparations. Two neuronal types were found and their quantitative features were studied. Golgi-type I neurons were medium to large cells with dense dendritic trees and dendritic protrusions and short hair-like appendages. They have somatic mean diameter of 30.8 μm (±9.4, n = 85). They have an average 100.3 dendritic branches, 48.97 dendritic branching points, and 58.85 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 3.1 μm (±1, n = 80), 1.85 μm (±0.8, n = 145), and 1.5 μm (±0.4, n = 160), respectively. Golgi-type II neurons were small to medium cells with few sparsely branching dendrites and dendritic stalked appendages with or without terminal swellings. They have somatic mean diameters of 22.2 μm (±5.8, n = 120). They have an average 33.76 dendritic branches, 16.49 dendritic branching points, and 21.97 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 1.6 μm (±0.86, n = 70), 1.15 μm (±0.55, n = 118), and 1 μm (±0.70, n = 95), respectively. These quantitative data may form the basis for further quantitative studies involving aging or some degenerative diseases that may affect cell bodies and/or dendritic trees of the Golgi-type I and/or Golgi-type II thalamic neurons.     

运动训练和停训对鲈鲤幼鱼游泳能力的影响

为探讨运动训练和停训对鲈鲤Percocypris pingi幼鱼运动能力的影响,将480尾(体质量为2.18g±0.12g,体长为5.33cm±0.09cm)鲈鲤幼鱼随机分为4组(每组120尾):对照组(C)、无氧训练组(An)、4BL·s^-1组(BL为体长)(H)和2BL·s^-1组(L)(H组和L组每天均训练8h),在15℃±2℃条件下持续训练30d后停训。分别在训练前(T0)、训练30d后(T30)、停训20d后(DT20)和停训50d后(DT50)测定鲈鲤幼鱼的临界游泳速度(Ucrit)和1.5Ucrit条件下的耐受时间。结果显示:(1)持续运动训练显著提高了鲈鲤幼鱼的有氧和无氧运动能力,而力竭运动训练只提高了鲈鲤幼鱼的无氧运动能力;(2)停训20d后,L组的Ucrit显著高于An组和C组,An组、H组和C组间的差异无统计学意义,而An组和H组的耐受时间仍显著高于对照组,L组和C组间的差异无统计学意义;(3)停训50d后,实验组和C组间Ucrit和耐受时间的差异均无统计学意义。因此,运动训练显著提高了鲈鲤幼鱼的有氧和无氧运动能力,但不同训练方式的提升效果及其维持时间不同。     

Exercise modulates the aortic renin-angiotensin system independently of estrogen therapy in ovariectomized hypertensive rats

The renin-angiotensin-system is an important component of cardiovascular control and is up-regulated under various conditions, including hypertension and menopause. The aim of this study was to evaluate the effects of swimming training and estrogen therapy (ET) on angiotensin-II (ANG II)-induced vasoconstriction and angiotensin-(1-7) [ANG-(1-7)]-induced vasorelaxation in aortic rings from ovariectomized spontaneously hypertensive rats. Animals were divided into Sham (SH), Ovariectomized (OVX), Ovariectomized treated with E2 (OE2), Ovariectomized plus swimming (OSW) and Ovariectomized treated with E2 plus swimming (OE2 + SW) groups. ET entailed the administration of 5 μg of 17β-Estradiol three times per week. Swimming was undertaken for sixty minutes each day, five times per week. Both, training and ET were initiated seven days following ovariectomy. Forty-eight hours after the last treatment or training session, the animals’ systolic blood pressures were measured, and blood samples were collected to measure plasma ANG II and ANG-(1-7) levels via radioimmunoassay. In aortic rings, the vascular reactivity to ANG II and ANG-(1-7) was assessed. Expression of ANG-(1-7) in aortic wall was analyzed by immunohistochemistry. The results showed that both exercise and ET increased plasma ANG II levels despite attenuating systolic blood pressure. Ovariectomy increased constrictor responses to ANG II and decreased dilatory responses to ANG-(1-7), which were reversed by swimming independently of ET. Moreover, it was observed an apparent increase in ANG-(1-7) content in the aorta of the groups subjected to training and ET. Exercise training may play a cardioprotective role independently of ET and may be an alternative to ET in hypertensive postmenopausal women.     

Functionally relevant neutrophilia in CD11c diphtheria toxin receptor transgenic mice

Transgenic mice expressing the diphtheria toxin receptor (DTR) in specific cell types are key tools for functional studies in several biological systems. B6.FVB-Tg(Itgax-DTR/EGFP)57Lan/J (CD11c.DTR) and B6.Cg-Tg(Itgax-DTR/OVA/EGFP)1Gjh/Crl (CD11c.DOG) mice express the DTR in CD11c(+) cells, allowing conditional depletion of dendritic cells. We report that dendritic-cell depletion in these models caused polymorphonuclear neutrophil (PMN) release from the bone marrow, which caused chemokine-dependent neutrophilia after 6-24 h and increased bacterial clearance in a mouse pyelonephritis model. We present a transgenic mouse line, B6.Cg-Tg(Itgax-EGFP-CRE-DTR-LUC)2Gjh/Crl (CD11c.LuciDTR), which is unaffected by early neutrophilia. However, CD11c.LuciDTR and CD11c.DTR mice showed late neutrophilia 72 h after dendritic cell depletion, which was independent of PMN release and possibly resulted from increased granulopoiesis. Thus, the time point of dendritic cell depletion and the choice of DTR transgenic mouse line must be considered in experimental settings where neutrophils may be involved.     

The area postrema: a cardiovascular control centre at the blood-brain interface?

The area postrema (AP) is one of the circumventricular organs of the brain and as such it is highly vascular and lacks the normal blood-brain barrier. Anatomical tracing studies have demonstrated afferent projections to AP originating from the paraventricular nucleus, lateral parabrachial nucleus (l-PBN), nucleus tractus solitarius (NTS), as well as the vagus nerve. AP neurons have been shown to project primarily to l-PBN, and NTS. Receptor localization studies have reported dense aggregations of many specific peptide receptors in AP including those for angiotensin II (ANG), atrial natriuretic peptide (ANP), and endothelin (ET). Electrical stimulation studies have shown that activation of AP neurons at low frequencies (less than 15 Hz) results in decreases in blood pressure and heart rate, while higher frequency (greater than 20 Hz) stimulation causes increases in blood pressure. These low frequency effects on blood pressure and heart rate appear to result from activation of separate components of the autonomic nervous system. Extracellular single unit recordings have identified two functionally separate populations of AP neurons: one responsive to circulating ANG and a second apparently responsive to changes in blood pressure. In addition, AP neurons are activated by increases in circulating ET. Afferent inputs to AP neurons from 1-PBN have separate excitatory (12% of AP neurons) or inhibitory (12% of AP neurons) effects on a relatively small proportion of AP neurons. In contrast, preliminary evidence suggests a much more broadly distributed excitatory input to approximately 70% of tested AP neurons originating from the aortic depressor nerve. These studies provide considerable evidence implicating the AP as a significant neural structure regulating the cardiovascular system.