中脑导水管周围灰质在大鼠血管源性头痛模型中的作用

目的研究中脑导水管周围灰质(PAG)在血管源性头痛如偏头痛涉及的伤害觉信息的传递中的作用。方法以雄性SD大鼠(体重为220~250g)为实验对象,在手术暴露其上矢状窦(SSS)后电刺激SSS区硬脑膜制作血管性头痛的动物模型;应用免疫组织化学染色技术,观察中脑PAG原癌基因蛋白质c-fos(Fos)和一氧化氮合酶(NOS)表达的变化。结果Fos免疫反应阳性神经元和NOS免疫反应阳性神经元主要位于中脑PAG的腹外侧区,阳性细胞数头侧至尾侧逐渐增多。空白对照组、假手术对照组、刺激组每张切片的Fos阳性神经元数分别为7.2±4.2、13.6±4.3、76.0±12.3;NOS阳性神经元数分别为35.0±3.5、42.3±4.2、162.0±11.6。结论刺激大鼠SSS区硬脑膜可激活PAG,提示PAG不但参与对于伤害性感觉信息传入后的下行调节,还通过上行投射纤维与疼痛中枢丘脑发生联系。PAG可能参与血管源性头痛如偏头痛的痛觉中枢调控。     

胃肠道伤害性刺激引起大鼠孤束核与中脑导水管周围灰质神经元表达FOS

为研究中脑导水管周围灰质（PAG）与孤束核（NTS）内脏伤害性信息传递和调控之间的相互关系，采用免疫荧光组织化学方法结合荧光金（FG）逆行追踪技术，观察了大鼠NTS和PAG之间相互投射神经元在给予胃肠道伤害性刺激后的FOS表达情况。给胃肠道以1％多聚甲醛的伤害性刺激后，FOS阳性细胞主要出现于中尾段NTS的内侧亚核；在PAG内，则主要出现于足段PAG的腹外侧区。将FG微量注射于PAG后，再给予动物刺激，发现NTS内部分FG逆行标记细胞同时为FOS阳性，它们主要分布于中尾段NTS的内侧亚核，双标细胞占FG标记细胞的十分之一左右。同上，将FG注射于中尾段NTS后再施予伤害性刺激，在PAG内发现有FOS阳性的FG道标细胞，它们集中分布于尾段PAG的腹外侧区，双标细胞约占FG标记细胞的五分之一。此外，在中缝背核内也发现有一定数且的双标细胞。本文结果提示PAG可能对NTS内内脏伤害性信息的传递具有调控作用。     

热应激时大鼠中脑导水管周围灰质Fos蛋白的表达

目的 探讨急性热应激（HS）后大鼠中脑导水管周围灰质Fos蛋白的表达情况。方法将大鼠分别置于24℃、34℃、38.5℃或42℃,湿度为60%的恒温恒湿舱内1h,断头取脑,常规切片,用亲合素-生物素-过氧化物酶复合物法（ABC）进行抗Fos蛋白的免疫组织化学染色。结果 对照组大鼠中脑导水管周围灰质内只发现很少数的Fos阳性细胞。置于34℃的大鼠中脑导水管周围灰质内Fos阳性细胞有所增加;38.5℃大鼠Fos阳性细胞明显增加,数量达到高峰;42℃大鼠Fos阳性细胞数明显减少。Fos阳性细胞主要分布于中脑导水管周围灰质的腹外侧区。结论 中脑导水管周围灰质,尤其是腹外侧区内神经元可能参与了对热应激反应的调节。     

LPS激发大鼠前脑神经元Fos和小胶质细胞OX42表达改变

目的 探讨单次腹腔注射LPS后前脑神经元和小胶质细胞的可塑性变化和相互关系。方法 应用抗Fos、抗TH或抗OX42单一、以及抗Fos／抗TH／抗OX42三重免疫组化标记方法，观察大鼠单次腹腔注射LPS后，Fos阳性神经元、Fos／TH阳性神经元、OX42阳性小胶质细胞在脑内的表达分布及时程变化，以及Fos阳性神经元或Fos／TH阳性神经元与OX42阳性小胶质细胞之间的关系。结果：Fos阳性神经元分布在额、顶皮质，扣带回和梨状皮质，外侧隔核腹侧部，杏仁中央核，海马CA2区、CA3区、齿状回，下丘脑室旁核、视上核、下丘脑外侧区和第三脑室周围灰质等。Fos阳性神经元在注射后30min出现表达，注射后1～3h为表达高峰。反应阳性小胶质细胞首先于脑室周围灰质出现，注射后6h达到高峰，胞体变大，突起变粗，OX42呈阳性深染，密集分布于Fos阳性神经元的表达区域。下丘脑Fos／TH／OX42三重染色切片显示：由LPS激活的Fos／TH阳性神经元周围被OX42阳性细胞包绕并接触，表明神经元和小胶质细胞在对LPS刺激的反应中关系密切。结论 在外周免疫刺激下，下丘脑、扣带回、梨状皮质和海马内的神经元和小胶质细胞可能参与免疫调节。     

大鼠脑干内的calbindin D—28K可能参与内脏伤害性信息传递或调控的形态学研究

为研究calbindinD 2 8K(CB)是否与内脏伤害性信息的传递或调控有关 ,应用免疫组织化学双重标记技术 ,对给予内脏伤害性刺激后大鼠脑干内表达Fos蛋白的CB免疫阳性神经元分布进行了观察。结果显示 :在孤束核 (NTS)、延髓腹外侧区 (VLM)、蓝斑 (LC)、臂旁外侧核 (LPB)、中脑导水管周围灰质腹外侧区 (vlPAG)等核团内均可见Fos/CB双标记神经元。双标记神经元分别占上述核团内Fos蛋白免疫阳性神经元数量的比例为12 .8% ,4 2 .7% ,4 8.1% ,14 .0 %和 13.9% ;占CB免疫标记阳性神经元数量的比例为 14 .3% ,2 4 .3% ,38.4 % ,6 .8%和 8.9%。研究结果提示 ,CB可能参与脑干内内脏伤害性信息的传递或调控。     

颈交感神经对中脑导水管周围灰质信号表达的影响

目的：通过电刺激大鼠上矢状窦区硬脑膜，观察颈上交感神经节（SCG）摘除术前、后中脑导水管周围灰质（PAG）一氧化氮合酶（NOS）阳性神经元数日的变化，以探讨交感神经系统在血管源性头痛如偏头痛伤害性信息传递巾的作用。方法：以雄性SD大鼠行颈上交感神经节摘除术后再手术暴露其上矢状窦（SSS），电刺激SSS区硬脑膜，应用免疫组织化学染色技术，观察PAG区域NOS表达的变化。结果：NOS免疫反应阳性神经元主要分布在PAG的腹外侧区，双侧对称。SCG摘除组NOS阳性神经元数目较假手术组明显增加。结论：颈交感神经系统通过PAG对痛觉的中枢调整参与了血管源性头痛如偏头痛中伤害性感觉信息的产生、传导及调节过程。     

大鼠脑干内的calbindin D-28K可能参与内脏伤害性信息传递或调控的形态学研究

为研究calbindin D-28K(CB)是否与内脏伤害性信息的传递或调控有关,应用免疫组织化学双重标记技术,对给予内脏伤害性刺激后大鼠脑干内表达Fos蛋白的CB免疫阳性神经元分布进行了观察.结果显示:在孤束核(NTS)、延髓腹外侧区(VLM)、蓝斑(LC)、臂旁外侧核(LPB)、中脑导水管周围灰质腹外侧区(vlPAG)等核团内均可见Fos/CB双标记神经元.双标记神经元分别占上述核团内Fos蛋白免疫阳性神经元数量的比例为12.8%,42.7%,48.1%,14.0%和13.9%;占CB免疫标记阳性神经元数量的比例为14.3%,24.3%,38.4%,6.8%和8.9%.研究结果提示,CB可能参与脑干内内脏伤害性信息的传递或调控.     

褪黑激素、5-羟色胺对大鼠中脑导水管周围灰质薄片神经元自发单位放电的影响(英文)

运用细胞外电生理记录方法，研究了褪黑激素（MEL）、5一羟色胺（5－HT）对大鼠中脑导水管周围灰质（PAG）薄片神经元自发放电的影响。PAG神经元对MEL和5－HT的主要反应分别为抑制和兴奋。MEL的效应能被5－HT的拮抗剂噻庚啶（CPD）所阻断。结果提示，MEL不仅能通过自身受体，而且部分通过5－HT受体起作用。     

大鼠延髓内脏带与下丘脑室旁核、视上核往返投射通路参与高渗调节反应的研究

目的探讨延髓内脏带(MVZ)与下丘脑室旁核(PVN)和视上核(SON)之间是否存在往返渗透压投射通路。方法通过给予大鼠饮用3%氯化钠的方法制作高渗刺激模型,并用WGA-HRP逆行追踪、抗Fos、抗酪氨酸羟化酶(TH)或加压素(VP)及胶质纤维酸性蛋白(GFAP)免疫组织化学相结合的四重标记方法,观察MVZ、PVN和SON中WGA-HRP、Fos、TH、VP和GFAP阳性分布及表达状况。结果高渗刺激后MVZ、PVN和SON内Fos阳性细胞明显增多;GFAP阳性结构也明显增多,其分布与Fos阳性细胞分布基本一致,表现为胞体肥大、突起粗长。星形胶质细胞(AST)紧密包绕在神经元周围形成神经元-AST复合体(N-ASC)。结论神经元和AST以N-ASC的形式共同参与渗透压调节反应,体内存在MVZ和SON或PVN之间往返的渗透压调节通路。     

Fos蛋白和Jun蛋白在犬颅脑枪弹伤局部脑组织的表达

目的　研究犬颅脑枪弹伤后脑神经元早期快反应基因c fos和c jun表达产物Fos蛋白和Jun蛋白的变化规律。方法　 2 0只杂种犬 ,随机分为正常对照组、损伤组。以德国小口径步枪子弹致犬颅脑贯通伤 (PCI)模型为对象 ,采用免疫组化法检测脑组织伤后 30min、2h、6h弹道挫伤区、震荡区及脑干神经元中Fos和Jun蛋白的表达。结果　对照组脑皮质神经元中Fos和Jun蛋白弱表达 ,弹道挫伤区、震荡区及脑干神经元中Fos和Jun蛋白表达于伤后 30min开始增加 ,2h达到高峰 ,6h逐渐下降。且Fos和Jun蛋白表达在弹道震荡区较挫伤区更为明显 (P <0 .0 5 )。结论　Fos蛋白和Jun蛋白在弹道挫伤区、震荡区及脑干神经元均有表达 ,c jun在脑组织内表达的分布范围及变化趋势与c fos基本一致 ,其表达是对损伤刺激的早期反应 ,可能是由Leao播散性抑制引起 ,并与细胞内外信号转导和细胞凋亡有关。     

Fos immunoreactivity in the rat brain following consummatory elements of sexual behavior: a sex comparison

In the present study a comparison was made between the distribution of Fos immunoreactivity in the brain of female and male rats following successive elements of sexual behavior. The distribution of Fos immunoreactivity following either mounting, eight intromissions or one or two ejaculations was compared with that in control animals. In both females and males, Fos immunoreactivity was induced in the medial preoptic nucleus, posteromedial part of the bed nucleus of the stria terminalis, posterodorsal part of the medial amygdala, and the parvicellular part of the subparafascicular thalamic nucleus. In addition, Fos immunoreactivity in females was induced in the ventrolateral part and the most caudoventral part of the ventromedial nucleus of the hypothalamus and in the premammillary nucleus. Differences between females and males were detected in the phases of sexual activity that resulted in Fos immunoreactivity in these brain areas, allowing more insight in the nature of the sensory and hormonal stimuli leading to the induction of Fos immunoreactivity. The posteromedial bed nucleus of the stria terminalis appears to be involved in chemosensory investigation, while specific distinct subregions are only activated following ejaculation. In addition, the parvicellular subparafascicular nucleus and the lateral part of the posterodorsal medial amygdala appear to be involved in the integration of viscero-sensory input. The neural circuitries underlying sexual behavior in males and females appear to be similar in terms of integration of sensory information. In males the medial preoptic nucleus may be regarded as the brain area where the integration of sensory and hormonal stimulation leads to the onset of male sexual behavior, while in females the ventrolateral part of the ventromedial hypothalamic nucleus appears to have this function. In addition, Fos immunoreactivity was distributed in distinct clusters in subregions within various brain areas in males and females. This was observed especially in the posteromedial bed nucleus of the stria terminalis and posterodorsal medial amygdala, but also in the parvicellular subparafascicular nucleus, ventromedial hypothalamic nucleus and ventral premammillary nucleus. It appears that relatively small subunits within these nuclei seem to be concerned with the integration of sensory and hormonal information and may play a critical role in sexual behavior.     

Induction of preconvulsive behavior and Fos expression by dopamine-induced nigral lesion in the rat

The substantia nigra pars reticulata (SNpr) has been proposed to play an important role in controlling the propagation and/or the generation of limbic seizures. Earlier work has shown that SN lesions have differential effects on seizure activity, suggesting that at least two discrete topographical regions mediate anticonvulsant or proconvulsant effects. The present investigation showed that exogenous dopamine (DA; 1.5–2.0 μmol) unilaterally injected into the anterior SNpr induced preconvulsive behavior (staring, immobilization, facial and mouth movements and wet-dog shakes). In addition, these rats showed Fos oncoprotein expression in the limbic system. These effects were observed in 90% of the rats with anterior SNpr DA injection. Rats with posterior SNpr injection did not show preconvulsive behavior nor Fos expression. These results show for the first time that unilateral DA lesion of the anterior portion of SNpr elicits Fos expression and preconvulsive behavior. In addition, the results suggest that lesion of the anterior and posterior regions of SNpr appear to exert different influences in the generation of preconvulsive behavior. The time course of behavior changes and Fos expression was also studied. ©1997 Elsevier Science B.V. All rights reserved.     

Fos expression in otolith-related brainstem neurons of postnatal rats following off-vertical axis rotation

To determine the critical time of responsiveness of developing otolith organ-related brainstem neurons and their distribution, Fos protein expression in response to off-vertical axis rotations (OVAR) was mapped in conscious Sprague Dawley rats from P5 to adulthood. OVAR was used to activate sequentially all utricular hair cells per 360 degrees revolution. We detected the coding of horizontal head positions in otolith organ-related neurons within the vestibular nucleus as early as P7. In the vestibular nuclear complex and its subgroups, the density of Fos-immunoreactive (Fos-ir) neurons increased steadily with age and reached the adult level by P21. In both labyrinthectomized rats subjected to OVAR and normal rats kept stationary, labeled neurons were found sporadically in the aforementioned brain regions in each age group, confirming that Fos labeling observed in neurons of normal experimental rats subjected to OVAR was due to otolith organ stimulation. Whereas OVAR-induced Fos-ir neurons were also first observed in vestibular-related brain areas, such as the prepositus hypoglossal nucleus, gigantocellular reticular nucleus, and locus coeruleus, of normal experimental rats at P7, those in the inferior olive were observed only from P14 onward. This indicates the unique maturation time of inferior olivary neurons in gravity-related spatial coding. In general, age-dependent increase in OVAR-induced Fos-ir neurons was observed in brain areas that received otolith inputs. The locus coeruleus was exceptional in that prominent OVAR-induced Fos-ir neuronal number did not change with maturation, and this was well above the low but significant number of Fos-ir neurons in control preparations. Taken together, our results suggest that neuronal subpopulations within the developing network of the horizontal otolith system provide an anatomical basis for the postnatal development of otolith organ-related sensorimotor functions. J. Comp. Neurol. 470:282-296, 2004.     

微量海人酸注入大鼠延髓网状背侧亚核诱导的Fos表达及其与NADPH-d的共存

目的：研究大鼠网状背侧亚核的功能传出通路及该通路上NADPH-d的分布。方法：将微量海人酸注入大鼠延髓网状背侧亚核，2h后灌注，脑片进行NADPH-d组织化学和Fos免疫组化染色。结果：Fos阳性细胞主要分布于中缝背核(DR)、中缝大核(NRM)、蓝斑(LC)、中脑导水管周围灰质腹外侧(vlPAG)和下丘脑室旁核。Fos／NADPH-d双标细胞主要分布于巨细胞网状核、下丘脑室旁核和中缝大核。结论：大鼠延髓网状背侧亚核与脊髓上中枢存在广泛的功能联系，而且在延髓网状背侧亚核的功能传出通路上有一氧化氮合酶的分布。     

Fos expression in response to dopamine D3‐preferring phenylpiperazine drugs given with and without cocaine

WC 44 and WC 10 are phenylpiperazines with low (23 fold) to moderate (42 fold) selectivity for dopamine D3 receptors (D3Rs) over D2Rs, respectively. WC 44 is a full D3R agonist in the forskolin‐stimulated adenylyl cyclase (AC) assay, whereas WC 10 has little efficacy. In contrast to their opposite effects in the AC assay, these drugs often produce similar behavioral effects, suggesting that the AC assay does not predict the efficacy of these drugs in vivo. Here, we examined whether Fos protein expression induced by these drugs would be more consistent with their behavioral effects in vivo. Rats received either vehicle, WC 10 (5.6 mg/kg, i.p.), WC 44 (10.0 mg/kg, i.p), cocaine (10.0 mg/kg, i.p.), or cocaine with WC 10 (5.6 mg/kg, i.p.) or with WC 44 (10.0 mg/kg, i.p). Locomotion was monitored for 90 min and the brains were harvested for immunohistochemistry. Both WC 10 and WC 44 decreased spontaneous and cocaine‐induced locomotion. Both compounds also increased Fos expression relative to saline in the dorsal striatum and nucleus accumbens core and shell, and relative to cocaine alone in the nucleus accumbens shell. The findings suggest that even though these compounds have different efficacy in the AC bioassy, they produce similar brain activation and attenuation of cocaine hyperlocomotion. Together with our previous research demonstrating that these compounds down‐shift the cocaine self‐administration dose‐effect function, the findings support the idea that D3R‐selective compounds may be useful for cocaine dependence medications development. Synapse 67:847–855, 2013 . © 2013 Wiley Periodicals, Inc.     

Participation of Fos protein at the nucleus tractus solitarius in inhibitory modulation of baroreceptor reflex response in the rat

We investigated the physiologic role of Fos protein at the nucleus tractus solitarius (NTS) in the modulation of baroreceptor reflex (BRR) in adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplements). Repeated and scheduled activation of the baroreceptors by transient hypertension induced by i.v. administration of phenylephrine (2.5, 5.0 or 10.0 μg/kg) resulted in a significant increase in Fos-like immunoreactivity (Fos-LI), primarily in the caudal part of the NTS. This increase in Fos-LI in the barosensitive NTS neurons was appreciably reduced by bilateral microinjection into the caudal NTS of an antisense oligonucleotide (20 pmol, 20 nl) designed to target a region of the c-fos mRNA that flanks the initiation codon (5′-129 to 143-3′). The same treatment also discernibly enhanced the BRR response, but elicited no appreciable effect on systemic arterial pressure or heart rate. On the other hand, bilateral application to the NTS of the corresponding sense oligonucleotide (20 pmol, 20 nl) or an antisense cDNA (20 pmol, 20 nl) that targeted a different site of the c-fos-mRNA (5′-135 to 149-3′) was ineffective. These results suggest that expression of the inducible c-fos gene in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of baroreflex control of blood pressure.     

Quantitative study of the coexpression of Fos and N-methyl-D aspartate (NMDA) receptor subunits in otolith-related vestibular nuclear neurons of rats

The expression of NMDA receptor subunits (NR1 and NR2A/B) was demonstrated immunocytochemically in otolith-related neurons within the vestibular nuclear complex and its subnuclei of conscious Sprague-Dawley adult rats. All experimental animals were subjected to constant velocity off-vertical axis rotation (OVAR). The rotating gravity vector during OVAR sequentially activates hair cells on all sectors of the utricular maculae; neurons so activated within the vestibular nuclei were denoted by the expression of Fos protein. Control animals, i.e., labyrinthectomized rats subjected to OVAR and normal rats that remained stationary, showed only a few sporadically scattered labeled neurons. In the brainstem of normal rats subjected to OVAR, a high density of Fos-immunoreactive (Fos-ir) neurons was found in the vestibular nuclear complex (namely, spinal vestibular nucleus, SpVe; medial vestibular nucleus, Mve; superior vestibular nucleus, SuVe) and subnuclei (namely, group x and group y), whereas a lower density was found in the lateral vestibular nucleus (LVe). A double-immunofluorescence study indicated that both NR1 and NR2A/B subunits were highly expressed in Fos-ir neurons within the vestibular nuclei. Fos/NR1 or Fos/NR2A/B double-labeled neurons constitute over three-quarters of the total number of Fos-ir neurons in SpVe, MVe, LVe, SuVe, and groups x and y. Our findings suggest that NMDA-type ionotropic glutamate receptors play a key role in the OVAR-induced neuronal activation of the vestibular nuclei, thus providing a morphological basis for further study of glutamatergic central otolith neurons and their involvement in sensorimotor regulation and autonomic functions of rats.     

Interactive effects of stimulation of D1 and D2 dopamine receptors on Fos expression in the lateral habenula

We have previously shown that systemic administration of non-selective dopamine agonists results in a pronounced expression of the proto-oncoprotein Fos within the lateral habenula. In the current study we examined the effects of selective D1 and D2 dopamine receptor agonists on habenular Fos expression. Rats were injected with various doses of the selective D2 agonist quinpirole (0, 0.62 or 2.5 mg/kg) either alone or in combination with various doses of the selective full D1 agonist A-77636 (0, 0.75 or 3.0 mg/kg). The selective agonists, by themselves, induced only small increases in Fos-like immunoreactivity within the lateral habenula, but combinations of the two drugs resulted in a very robust response. These findings indicate that D1 and D2 receptor agonists interact to induce Fos expression within the habenula and that the nature of this interaction differs from that reported in the striatum and the globus pallidus.