Motor cortical control of cardiovascular bulbar neurones projecting to spinal autonomic areas

There is evidence that the motor cortex is involved in cardiovascular adjustments associated with somatic motor activity, as it has functional connections with the ventrolateral medulla, a brainstem region critically involved in the control of blood pressure and the regulation of plasma catecholamine levels. The ventrolateral medulla sends projections to the spinal intermediolateral nucleus, where preganglionic neurones controlling heart and blood vessels (T2 segment) and adrenal medulla (T8 segment) are found. The aim of the present study was to determine whether electrical stimulation of the rat motor cortex induces cardiovascular responses and Fos expression in ventrolateral medulla neurones projecting to the T2 and T8 segments. After a set of experiments designed to record cardiovascular parameters (blood pressure and plasma catecholamine levels), injections of retrograde tracer (Fluorogold) were performed in the intermediolateral nucleus of two groups of rats, at the T2 or at the T8 segmental levels. Five days later, the motor cortex was stimulated in order to induce Fos expression in the ventrolateral medulla. Stimulation of the motor cortex induced: (1). hypotension and a significant decrease in plasma noradrenaline levels, and (2). a significant increase in the number of the double-labelled neurones in the rostral ventrolateral medulla projecting to T2. These data demonstrate that cardiovascular adjustments, preparatory to, or concomitant with, motor activity may be initiated in the motor cortex and transmitted to cardiac and vasomotor spinal preganglionic neurones, via the ventrolateral medulla.     

Increased synaptic input to gonadotropin releasing hormone cells in preoptic area grafts that support reproductive development in female hypogonadal mice

Ultrastructural studies have established that gonadotropin releasing hormone (GnRH) neuronal cell bodies receive sparse synaptic input compared to other neuronal cell types. In the present studies, immunocytochemistry for the presynaptic marker synaptophysin, coupled with confocal microscopy, was employed to evaluate whether there was a difference in synaptic input to GnRH cells within preoptic area grafts (hypogonadal, HPG; preoptic area, POA) in hypogonadal female mice that did or did not show ovarian development. GnRH cells in HPG/POA mice with ovarian development exhibited significantly higher numbers of synaptophysin immunoreactive (syn-IR) appositions as compared with HPG/POA mice without ovarian development. This suggests that synaptic input to the grafted GnRH cells is important for the correction of reproductive functions in HPG/POA mice. Following mating, Fos immunoreactivity was present in several GnRH cells in HPG mice with successful POA grafts, indicating the establishment of neuronal projections conveying somatosensory information to the GnRH cells in these mice. The presence of a higher number of syn-IR appositions to GnRH cells in the successful grafts supports this hypothesis.     

MTBE对大鼠中枢神经系统Fos蛋白的影响

目的通过研究甲基叔丁基醚(MTBE)对大鼠中枢神经系统Fos蛋白的影响,探讨MTBE对中枢神经系统急性毒作用部位。方法54只健康成年SD大鼠,体重180～220g,随机分为9组,腹腔注射MTBE原液染毒,以未染毒为对照,染毒剂量分别为700、1050、1400mg/(kg·bw),染毒后用免疫组织化学方法检测Fos蛋白的表达并用相对灰度值定量。结果未染毒对照组脑组织神经元内仅有少量Fos蛋白表达,MTBE急性染毒后在大脑皮质、丘脑、下丘脑、小脑皮质神经元内Fos蛋白表达均有明显增多,Fos蛋白表达的相对灰度值随着MTBE染毒剂量的增加,其表达逐渐增强,其中MTBE对大脑皮质、小脑皮质的毒作用较丘脑、下丘脑更为明显;各部位Fos蛋白在MTBE染毒后0.5h时表达开始增加,1.0h达到高峰,2.0h时开始减弱,8.0h时Fos蛋白表达恢复到染毒前水平。结论MTBE可诱导大脑皮质、小脑皮质、丘脑和下丘脑Fos蛋白的表达增强,大脑皮质、小脑皮质、丘脑和下丘脑是MTBE的急性毒作用部位。     

缺血再灌注大鼠心肌Fos蛋白表达及川芎嗪的作用

目的：研究大鼠心肌缺血再灌注（ＭＩＲ）时Ｆｏｓ蛋白表达与其病理组织学改变,并观察川芎嗪（ＴＭＰ）对ＭＩＲ时Ｆｏｓ蛋白表达的作用。方法：采用大鼠ＭＩＲ模型,用免疫组化ＡＢＣ法检测ＭＩＲ过程中不同时期Ｆｏｓ蛋白表达并与病得组织学改变进行对照分析．结果：（１）非缺血心肌无Ｆｏｓ蛋白表达,ＭＩＲ６０ｍｉｎ可诱导Ｆｏｓ蛋白表达,９０ｍｉｎ时达高峰,主要分布在心外膜侧。（２）与ＭＩＲ大鼠相比,ＴＭＰ干预缺血心     

Age-related increase inc-fos expression in the sympathetic neurons of the rat superior cervical ganglion

C-fos expression was studied immunocytochemically in sympathetic neurons of the rat superior cervical ganglion (SCG). Fos-like immunoreactivity was confined to the principal neurons of the ganglion and was exclusively localized within their nuclei. In 2-month-old rats, the immunoreactivity was detected in 1.2% of the principal neurons with a density of 4.95 Fos-positive cells/mm² of ganglion area. This proportion increased with age and reached a value which was 6.5-fold higher in the 26-month-old rats than that in the young adult. A density of 24.5 Fos-positive cells/mm² of ganglion area was seen in the 26-month-old animals. The age-enhancedc-fos expression suggests that Fos may be involved in regulation of the genetic events associated with the adaptive changes in neuronal activity of the sympathetic ganglion during aging.     

Stress-opioid interactions: a comparison of morphine and methadone

The utility of methadone and morphine for analgesia and of methadone for substitution therapy for heroin addiction is a consequence of these drugs acting as opioid receptor agonists.We compared the cataleptogenic and antinociceptive effects of single subcutaneous doses of methadone hydrochloride (1–4 mg/kg) and morphine sulfate (2.5–10 mg/kg) using catalepsy and hot-plate tests, and examined the effects of the highest doses of the drugs on Fos protein expression in selected brain regions in male Sprague-Dawley rats. Methadone had greater cataleptogenic and analgesic potency than morphine. Fos immunohistochemistry revealed substantial effects on the Fos response of both the stress induced by the experimental procedures and of the drug exposure itself. There were three response patterns identified: 1) drug exposure, but not stress, significantly elevated Fos-positive cell counts in the caudate-putamen; 2) stress alone and stress combined with drug exposure similarly elevated Fos-positive cell counts in the nucleus accumbens and cingulate cortex; and 3) methadone and morphine (to a lesser extent) counteracted the stimulatory effect of nonpharmacological stressors on Fos protein expression in the somatosensory cortex barrel field, and Fos-positive cell counts in this region correlated negatively with both the duration of catalepsy and the latency time in the hot-plate test. The overlap between brain regions reacting to nonpharmacological stressors and those responding to exogenous opioids suggests that stress contributes to opioid-induced neuronal activation.     

Acute muscle inflammation enhances the monosynaptic reflexes and c-fos expression in the feline spinal cord.

The aim of this research was to study the changes of the motor reflex activity (monosynaptic reflex (MSR) of the flexor and extensor muscles) and Fos immunoreactivity in lumbo-sacral spinal cord after acute induced myositis of m. gastrocnemius-soleus (GS). The experiments were carried out on ischaemic decerebrated, spinalized in C1 cats. After infiltration of the GS muscle with carrageenan (2%) MSRs of flexors and extensors showed a significant increase in amplitude +127+/-24.5% and +155+/-28.5%, respectively, p<0.05. The exposed effect was initiated within 30 min and achieved a maximum 2.8h after the intramuscular injections of carrageenan. After analysis of dynamics of the MSRs, animals were perfused and c-fos expression in the spinal segments L6-S1 was evaluated. In comparison to sham-operated animals, the number of Fos-immunoreactive (Fos-ir) cells was noticeably increased in the lumbar cord of cats with carrageenan-induced myositis. The labeled cells were concentrated in the ipsilateral laminae I/II, neck of the dorsal horn (V/VI) and intermediate zone (VII), however, clear predominance of their concentration was found in the deep laminae. The effect of muscle inflammation was also expressed as a significant decline in the number of NADPH-d-reactive cells (p<0.05) in ipsilateral laminae I/II of L6/L7. The results show that the input from acutely inflamed muscles may induce an increase of the reflex responsiveness of flexors and extensors which is not mediated via the gamma-spindle-loop and which coincides with a significant increase in c-fos expression in the deep laminae of the lumbar spinal cord.     

A minimal stress model for the assessment of electroacupuncture analgesia in rats under halothane.

The use of anesthetics in acupuncture analgesia is controversial. We evaluate a steady-state light anesthesia model to test whether minimal stress manipulation and reliable measurement of analgesia could be simultaneously achieved during electroacupuncture (EA) in animals. A series of experiments were performed. Firstly, EA compliance and tail-flick latencies (TFL) were compared in rats under 0.1%, 0.3%, 0.5%, 0.7%, or 1.1% halothane for 120min. Under 0.5% halothane, TFL were then measured in groups receiving EA at intensity of 3, 10 or 20 volt (V), 1 or 2mg/kg morphine, 20V EA plus naloxone, or control. Subsequently, the effect of EA on formalin-induced hyperalgesia was tested and c-fos expression in the spinal dorsal horn was analyzed. Rats exhibited profound irritable behaviors and highly variable TFL under 0.1% or 0.3% halothane, as well as a time-dependent increase of TFL under 0.7% or 1.1% halothane. TFL remained constant at 0.5% halothane, and needle insertion and electrical stimulation were well tolerated. Under 0.5% halothane, EA increased TFL and suppressed formalin-induced hyperalgesia in an intensity-dependent and naloxone-reversible manner. EA of 20V prolonged TFL by 74%, suppressed formalin-induced hyperalgesia by 32.6% and decreased c-fos expression by 29.7% at the superficial and deep dorsal horn with statistically significant difference. In conclusion, 0.5% halothane provides a steady-state anesthetic level which enables the humane application of EA stimulus with the least interference on analgesic assessment. This condition serves as a minimal stress EA model in animals devoid of stress-induced analgesia while maintaining physiological and biochemical response in the experiment.     

彩色多普勒超声对胎鼠大脑Fos蛋白表达影响的实验研究

目的 探讨诊断用彩色多普勒超声对胎鼠中枢神经系统的影响。方法 利用彩超照射孕18天大鼠子宫体表投影区，滑行照射30min，间隔不同时间留取胎鼠脑组织标本，分为照射后即刻、30min、2h、4h、8h及24h共6组及各自的对照组。应用免疫组化方法检测Fos蛋白的表达及出现的时间顺序。结果 ①照射后即刻及30min组仅见极少量着色浅淡的Fos阳性细胞，照射后2h出现密集分布的深染Fos阳性细胞，照射后4h及8h阳性细胞数逐渐下降，而照射后24h再次出现Fos蛋白高表达。②对照组各时间点均未见着色的Fos阳性细胞。结论 诊断用的彩超照射孕鼠30min，可激活胎鼠脑组织c-fos基因，并诱导其转录和表达，其高表达时间出现于照射后2h及24h。