P物质受体在大鼠纹状体边缘区内的表达

我们以前的工作观察到纹状体边缘区内有密集的P物质纤维及终末分布,本用原位杂交和免疫组织化学方法研究了大鼠纹状体边缘区内P物质受体（SPR）的表达及分布,原位杂交结果发现P物质mRNA阳性杂交信号在纹状体内的分布不均匀,尾壳核内只有少量中等大小的阳性胞体,苍白球内只有少量较大的阳性胸体,而在尾壳核和苍白球之间的边缘区部位则可见许多中等大小的梭形阳性神经元胞体,并呈现密集的带关分布。免疫组织化学结果观察到P物质阳性神经元胞体在纹状体内的分布与原位杂交结果一致。推测大鼠纹体边缘区内可以合成P物质受体,具有接受和整合P物质神经递质的功能,推测边缘区内SPR神经元可能对SP递质的接受、调节有重要作用。     

友鼠外侧膝状体中继神经元HRP示踪结合谷氨酸免疫组织化学研究

采用 HRP逆行追踪结合谷氨酸免疫组织化学方法观察大鼠外侧膝状体背侧核 (d L GN)中继神经元的化学递质。光镜下 HRP标记细胞与谷氨酸免疫阳性细胞清晰可辩。HRP单标记细胞位于外侧膝状体背侧核内 ,胞浆及树突基部充满棕色颗粒。免疫金银法 (IGSS)单标记的谷氨酸免疫阳性神经元分布于外侧膝状体背侧核与腹侧核 ,胞体内充满黑色银颗粒。在外侧膝状体背侧核内可见 HRP和谷氨酸双标记细胞 ,其数目占 HRP标记细胞总数的 70 .9± 6 .4%。本文提示 ,谷氨酸可能是外侧膝状体背侧核投射至视皮质的中继神经元的神经递质之一。     

AMPA受体与谷氨酸在大鼠三叉神经尾侧亚核内分布的免疫组织化学研究

本文用免疫组织化学ＡＢＣ法调查了４种ＡＭＰＡ受体亚单位（ＧｌｕＲ１、２／３、４）和谷氨酸（Ｇｌｕ）在大鼠三叉神经尾侧亚核（Ｖｃ）内的分布及其匹配关系。我们发现,ＧｌｕＲ１和２／３免疫阳性胞体和纤维密集分布于Ｖｃ的Ⅱ层和Ⅲ层外侧部,在Ｖｃ的其余各层呈散在性分布。ＧｌｕＲ４免疫阳性胞体和纤维在Ｖｃ各层均无分布。Ｇｌｕ免疫阳性胞体分布于Ｖｃ各层,尤以浅层（Ⅰ、Ⅱ层）密集,Ｇｌｕ免疫阳性纤维及终末结构主要分布于Ｖｃ浅层。结果表明,Ｇｌｕ免疫阳性纤维及终末样结构与ＡＭＰＡ受体免疫阳性胞体和纤维在Ｖｃ浅层的分布总体上是相互匹配的,但ＡＭＰＡ受体各亚单位在Ｖｃ内的分布存在明显的差异。本文提示,Ｖｃ内的Ｇｌｕ可能通过作用于不同的ＡＭＰＡ受体亚单位而发挥其多种生理功能     

一氧化氮合酶在豚鼠听觉核团的分布

为了研究一氧化氮合酶（ｎｉｔｒｉｃｏｘｉｄｅｓｙｔｈａｓｅ,ＮＯＳ）在听觉核团的分布特点,探讨一氧化氮（ｎｉｔｒｉｃｏｘｅｄｅ,ＮＯ）在听觉径路中的作用,本文采用ＮＡＤＰＨ硫辛酸胺脱氢酶（ＮＡＤＰＨ－ｄ）组织化学方法,研究了豚鼠听觉核团内ＮＯＳ的分布。结果发现,在各级听觉传入核团,均有ＮＯＳ阳性神经元,而上橄榄复合体ＮＯＳ反应阴性。耳蜗核ＮＯＳ阳性神经元主要集中在耳蜗后腹核,为圆形或椭圆形双极神经元。下丘ＮＯＳ阳性反应神经元位于下丘中央核团,胞体形状和大小不一。内侧膝状体背侧核ＮＯＳ阳性神经元相对集中,多为双极神经元,部分神经元突起很长,散在阳性纤维,部分阳性纤维穿行于内侧膝状体背侧核与内侧膝状体之间。本研究提示,ＮＯ可能是听觉中枢的神经递质或调质,参与声信号传递的调节。     

大鼠下丘脑内一氧化氮合酶阳性神经元的分布

用ＮＡＤＰＨ－ｄ组织化学方法观察了大白鼠下丘脑内一氧化氮合酶（ＮＤＳ）阳性神经元的分布及形态特征。结果显示：在视上核、室旁核的大细胞部、环状核、穹窿周核、下丘脑外侧区、下丘脑腹内侧核、下丘脑背内侧核、乳头体区大部分核团均可见一氧化氮合酶阳性神经元聚集成团。在视前内侧区、视前外侧区、下丘脑前区、下丘脑背侧区、下丘脑后区、室周核、室旁核小细胞部及穹窿内可见散在的一氧化氮合酶阳性神经元。室周核内可见呈阳性反应的接触脑脊液神经元的胞体及突起。一氧化氮合酶阳性神经元大多可见突起,有的突起上可见１～２级分支,并可见膨体。下丘脑大部分区域内可见阳性神经纤维。弓状核内可见许多弧形纤维连于第三脑室室管膜和正中隆起。     

中国树鼠句伏隔核促肾上腺皮质激素释放激素能神经元免疫组织化学研究

应用免疫组织化学碱性磷酸酶标Ａ蛋白（ＰＡＡＰ）技术在光镜水平研究中国树鼠句伏隔核内促肾上腺皮质激素释放激素（ＣＲＦ）能神经元的形态和分布特点。结果显示,该核内ＣＲＦ免疫反应阳性神经元胞体多数呈多边形、圆形或卵圆形,梭形极少;直径多数为１３－１９ｕｍ,少数＜１３ｕｍ;胞质免疫反应强度不等。对左右侧伏隔核内ＣＲＦ免疫反应阳性神经元数目、胞体大小、形态和免疫反应强度进行分析,除免疫反应强阳性神经元计数项（Ｐ＜００１）外,其他项都无显著意义。ＣＲＦ免疫反应阳性神经元在伏隔核内分布不均,主要位于该核的前半段背侧区,核芯区较少     

猫下丘中央核5-HT、P物质和星形胶质细胞年龄相关变化

目的比较研究青年猫与老年猫下丘中央核(CIC)5-羟色氨(5-HT)、P物质(SP)能神经元及星形胶质细胞年龄性变化,探索老年个体听力下降的神经机制。方法 Nissl染色显示下丘神经元,免疫组织化学ABC法显示5-HT、SP和胶质纤维酸性蛋白(GFAP)免疫反应(immunoreactive,IR)细胞。光镜下观察、拍照,对神经元和5-HT、SP及GFAP免疫反应细胞分别计数并换算成密度,测量其IR细胞直径取平均值,以及它们的阳性反应平均灰度值。结果 5-HT-IR、SP-IR和GFAP-IR细胞、阳性纤维及其终末在青年猫及老年猫下丘中央核均有分布。与青年猫相比,老年猫下丘中央核5-HT密度均显著下降(P<0.01),胞体直径明显减小(P<0.01),阳性反应明显减弱(阳性反应强度与灰度值呈负相关),SP-IR神经元和星形胶质细胞密度却显著增大,阳性反应显著增强。结论在衰老过程中猫下丘神经元尤其是5-HT能神经元有显著丢失现象,提示5-HT能神经元显著减少导致下丘听觉信息传递功能减弱,可能引起老年个体听觉功能衰退的重要原因;SP能神经元和星形胶质细胞密度显著增大,可能起到延缓衰老的作用。     

代谢型谷氨酸受体5与白细胞介素1受体Ⅰ型在大鼠大脑皮质及海马神经元的共存

目的 研究代谢型谷氨酸受体5(mGluR5)和白细胞介素1受体I型(IL-1RI)在大鼠大脑皮质和海马的分布及共存状况。方法 采用相邻切片的免疫细胞化学双标法,在两张相邻脑冠状切片上分别显示mGluR5与IL-1RI的免疫组化染色结果,通过显微摄像确定mGluR5／IL-1RI双标神经元。结果 切片上mGluR5阳性产物为蓝黑色,定位于细胞膜上;IL-1RI阳性产物为棕黄色,主要定位于细胞膜,也存在于神经元内。在大鼠大脑皮质及海马锥体细胞层均存在较丰富的mGluR5及IL-1RI阳性神经元。在大脑皮质,有部分神经元内mGluR5与IL-1RI共存;在海马锥体细胞层,mGluR5及n1RI阳性反应细胞密集,分布区重叠,很可能也存在二共存的神经元。结论 大鼠大脑皮质内存在mGluR5及IL-1RI共存神经元。本研究的结果为免疫神经调质在神经元内相互作用提供了形态学依据。     

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。     

降钙素基因相关肽、P物质、甘丙肽和γ-氨基丁酸免疫阳性细胞在大鼠结合臂旁核的分布

应用免疫细胞化学ABC技术观察了降钙素基因相关肽,P物质、甘丙肽和γ-氨基丁酸免疫阳性胞体在大鼠结合臂旁核中的分布。降钙索基因相关肽阳性神经元分布于臂旁内侧核的腹侧部及外内侧亚核、臂旁外侧核的外外侧亚核、极外侧亚核,背外侧亚核及上外侧亚核,也分布于KllikerFuse核。P物质阳性胞体分布于臂旁内侧核内侧部和外内侧亚核、臂部外侧核的外外侧亚核及极外侧亚核,在腹外侧亚核中亦见个别细胞分布。甘丙肽阳性细胞的分布较为广泛,分布于臂旁外侧核和臂旁内侧核所有的亚核及Klliker-Fuse核中,γ-氨基丁酸阳性神经元在中尾部臂旁核中分布于臂旁外侧核背内侧部包括背外侧亚核、腹外侧亚核、内外侧亚核及结合臂背侧部;在嘴部和中嘴部臂旁核,GABA阳性胞体除位于臂旁外侧核背内侧部的背外侧亚核、腹外侧亚核、中央外侧亚核、上外侧亚核及内外侧亚核外,也出现于腹外侧部的外外侧亚核、臂旁内侧核内侧部及Klliker-Fuse核。     

Cellular localization of a metabotropic glutamate receptor in rat brain.

In rat brain, the cellular localization of a phosphoinositide-linked metabotropic glutamate receptor (mGluR1 alpha) was demonstrated using antibodies that recognize the C-terminus of the receptor. mGluR1 alpha, a 142 kd protein, is enriched within the olfactory bulb, stratum oriens of CA1 and polymorph layer of dentate gyrus in hippocampus, globus pallidus, thalamus, substantia nigra, superior colliculus, and cerebellum. Lower levels of mGluR1 alpha are present within neocortex, striatum, amygdala, hypothalamus, and medulla. Dendrites, spines, and neuronal cell bodies contain mGluR1 alpha. mGluR1 alpha is not detectable in presynaptic terminals. mGluR1 alpha and ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits show differential distributions, but in Purkinje cells, mGluR1 alpha and specific AMPA receptor subunits colocalize. The postsynaptic distribution of mGluR1 alpha is consistent with postulated physiological roles of this subtype of glutamate receptor.     

Distribution of neurotensin-like immunoreactive cell bodies and fibers in the brainstem of the adult male cat

We studied the distribution of cell bodies and fibers containing neurotensin in the brainstem of the cat using an indirect immunoperoxidase technique. A high or moderate density of immunoreactive perikarya was found in the interpeduncular nucleus, inferior colliculus, nucleus of the brachium of the inferior colliculus and in the lateral tegmental field. Moreover, a high density of neurotensin-immunoreactive fibers was observed in the periaqueductal gray, locus coeruleus and in the marginal nucleus of the brachium conjunctivum. The interpeduncular nucleus, nucleus of the solitary tract and the dorsal motor nucleus of the vagus contained a moderate density of immunoreactive fibers.     

A light and electron microscopic study of glutamate receptors in the monkey subthalamic nucleus

The distribution of glutamate receptors in the monkey subthalamic nucleus was studied using affinity purified polyclonal antibodies to GluR1, phosphorylated GluR1, GluR2/3, NMDAR1, mGluR1a and mGluR5. Intense staining for both the unphosphorylated and the phosphorylated forms of the AMPA receptor subunit GluR1 was observed in the cell bodies and proximal dendrites of neurons in this nucleus. In comparison to GluR1, less intense staining for GluR2/3 was observed in the cell bodies and processes. NMDAR1 immunoreactivity was present in cell bodies and large numbers of small diameter dendrites. Light staining was observed in cell bodies with mGluR1a and no staining was observed on cell bodies with mGluR5. The neuropil, however, contained many processes that were labeled for mGluR1a or mGluR5. Electron microscopy showed that label was present in cytoplasmic locations in cell bodies and dendrites, in addition to components of the synaptic region, in sections stained for GluR1, GluR2/3 and NMDAR1. In contrast, very lightly labeled or unlabeled cell bodies but labeled dendrites and axon terminals, was observed in sections stained for mGluR1a and mGluR5. In addition to neural processes, occasional astrocytic processes were also labeled for mGluR5. Of the immunogold particles that were associated with components of the synaptic region, label for ionotropic glutamate receptors was mostly present on postsynaptic densities, whilst that for metabotropic glutamate receptors was mostly present in a perisynaptic location. The ratio of GluR1/GluR2 messenger RNAs has been reported to increase in the aged hippocampus (PAGLIUSI, S. R., GERRARD, P., ABDALLAH, M., TALABOT, D. & CATSICAS, S. (1994) Neuroscience 61, 429–433.), and it is possible that a similar change in the ratio of GluR1 and GluR2 may occur in neurons of the subthalamic nucleus with age. It is postulated that this could result an increase in calcium permeability via AMPA receptors, and an enhancement of excitatory transmission in this nucleus.     

Alpha-neo-endorphin-like immunoreactivity in the cat brain stem

This paper examines the distribution of fibers and cell bodies containing alpha-neo-endorphin in the cat brain stem by using an indirect immunoperoxidase technique. A high or moderate density of immunoreactive cell bodies was found in the superior central nucleus, nucleus incertus, dorsal tegmental nucleus, nucleus of the trapezoid body, and in the laminar spinal trigeminal nucleus, whereas a low density of such perikarya was observed in the inferior colliculus, nucleus praepositus hypoglossi, dorsal nucleus of the raphe, nucleus of the brachium of the inferior colliculus, and in the nucleus of the solitary tract. The highest density of immunoreactive fibers was found in the substantia nigra, dorsal motor nucleus of the vagus, nucleus coeruleus, lateral tegmental field, marginal nucleus of the brachium conjunctivum, and in the inferior and medial vestibular nuclei. These results indicate that alpha-neo-endorphin is widely distributed in the cat brain stem and suggest that the peptide could play an important role in several physiological functions, e.g., those involved in respiratory, cardiovascular, auditory, and motor mechanisms.     

Distribution and Developmental Regulation of Metabotropic Glutamate Receptor 7a in Rat Brain

Abstract: To determine the regional and cellular distribution of the metabotropic glutamate receptor mGluR7a, we used rabbit anti-peptide polyclonal-targeted antibodies against the C-terminal domain of mGluR7a. Here we report that immunocytochemistry at the light-microscopic level revealed that mGluR7a is widely distributed throughout the adult rat brain, with a high level of expression in sensory areas, such as piriform cortex, superior colliculus, and dorsal cochlear nucleus. In most brain structures, mGluR7a immunoreactivity is characterized by staining of puncta and fibers. However, in some regions, including the locus ceruleus, cerebellum, and thalamic nuclei, both cell bodies and fibers are immunopositive. The changes in levels of mGluR7a during development were investigated with immunoblotting and immunocytochemical analysis. Immunoblot analysis revealed that the levels of mGluR7a are differentially regulated across brain regions during postnatal development. In cortical regions (hippocampus, neocortex, and olfactory cortex), mGluR7a levels were highest at postnatal day 7 (P7) and P14, then declined in older rats. In contrast, mGluR7a levels were highest at P7 in pons/medulla and cerebellum and decreased markedly between P7 and P14. In these regions, mGluR7a immunoreactivity was at similar low levels at P14 and P21 and in adults. Immunocytochemical analysis revealed that staining for mGluR7a was exceptionally high in fiber tracts in P7 animals relative to adults. Furthermore, the pattern of mGluR7a immunoreactivity in certain brain structures, including cerebellum, piriform cortex, and hippocampus, was significantly different in P7 and adult animals. In summary, these data suggest that mGluR7a is widely distributed throughout the rat brain and that this receptor undergoes a dynamic, regionally specific regulation during postnatal development.     

D4 Dopamine and Metabotropic Glutamate Receptors in Cerebral Cortex and Striatum in Rat Brain

The characterization of the functional interactions between the metabotropic glutamate receptors (mGluR) and the dopaminergic (DR) receptors in the corticostriatal projections may provide a possible interpretation of synaptic events in the basal ganglia. It has been suggested that presynaptic D2-type receptor located on glutamatergic corticostriatal neurons regulates the release of glutamate. In a first approach we have studied the cellular distribution of the D4R and the mGluRs in cerebral cortex and striatum employing immunocytochemistry. D4R positive neurons were particularly numerous in medial prefrontal cortex mainly occupying layers II and III. An even distribution was found on small round-shaped neurons in the striatum. Group I mGluR1-like immunoreactivity (mGluR1-LI) was found in medial and deep layers of the cerebral cortex while group III mGluR4a labeled more superficial layers; group II mGluR2/3 signal was intense on fine fibers with a punctate appearance. In the striatum, mGluR1 and mGluR2/3 stained mainly fibers while mGluR4a labeled round shaped cell bodies. After lateral ventricular injection of colchicine, an axonal transport and firing activity blocker, D4R labeling significantly increased in cerebral cortex and decreased in the striatum. mGluR1 and mGluR4a signal decreased in cerebral cortex and only mGluR4a signal decreased in the striatum. These results support previous reports indicating a presynaptic localization of D4R in the striatum. In contrast, striatal mGluR1 appears to be a postsynaptic receptor probably synthesized in situ. Our results do not support the hypothesis of a colocalization of D4 receptor and one or more of the metabotropic glutamatergic receptors studied here.     

Calcitonin gene-related peptide: detailed immunohistochemical distribution in the central nervous system

With the use of an antiserum generated in rabbits against synthetic human calcitonin gene-related peptide (CGRP) the distribution of CGRP-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system. A detailed stereotaxic atlas of CGRP-like neurons was prepared. CGRP-like immunoreactivity was widely distributed in the rat central nervous system. CGRP positive cell bodies were observed in the preoptic area and hypothalamus (medial preoptic, periventricular, anterior hypothalamic nuclei, perifornical area, medial forebrain bundle), premamillary nucleus, amygdala medialis, hippocampus and dentate gyrus, central gray and the ventromedial nucleus of the thalamus. In the midbrain a large cluster of cells was contained in the peripeduncular area ventral to the medial geniculate body. In the hindbrain cholinergic motor nuclei (III, IV, V, VI, VII XII) contained CGRP-immunoreactivity. Cell bodies were also observed in the ventral tegmental nucleus, the parabrachial nuclei, superior olive and nucleus ambiguus. The ventral horn cells of the spinal cord, the trigeminal and dorsal root ganglia also contained CGRP-immunoreactivity. Dense accumulations of fibers were observed in the amydala centralis, caudal portion of the caudate putamen, sensory trigeminal area, substantia gelatinosa, dorsal horn of the spinal cord (laminae I and II). Other areas containing CGRP-immunoreactive fibers are the septal area, nucleus of the stria terminalis, preoptic and hypothalamic nuclei (e.g., medial preoptic, periventricular, dorsomedial, median eminence), medial forebrain bundle, central gray, medial geniculate body, peripeduncular area, interpeduncular nucleus, cochlear nucleus, parabrachial nuclei, superior olive, nucleus tractus solitarii, and in the confines of clusters of cell bodies. Some fibers were also noted in the anterior and posterior pituitary and the sensory ganglia. As with other newly described brain neuropeptides it can only be conjectured that CGRP has a neuroregulatory action on a variety of functions throughout the brain and spinal cord.     

Immunohistochemical mapping of galanin-like neurons in the rat central nervous system

Using an antiserum generated in rabbits against synthetic galanin (GA) and the indirect immunofluorescence method, the distribution of GA-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system (CNS) and a detailed stereotaxic atlas of GA-like neurons was prepared. GA-like immunoreactivity was widely distributed in the rat CNS. Appreciable numbers of GA-positive cell bodies were observed in the rostral cingulate and medial prefrontal cortex, the nucleus interstitialis striae terminalis, the caudate, medial preoptic, preoptic periventricular, and preoptic suprachiasmatic nuclei, the medial forebrain bundle, the supraoptic, the hypothalamic periventricular, the paraventricular, the arcuate, dorsomedial, perifornical, thalamic periventricular, anterior dorsal and lateral thalamic nuclei, medial and central amygdaloid nuclei, dorsal and ventral premamillary nuclei, at the base of the hypothalamus, in the central gray matter, the hippocampus, the dorsal and caudoventral raphe nuclei, the interpeduncular nucleus, the locus coeruleus, ventral parabrachial, solitarii and commissuralis nuclei, in the A1, C1 and A4 catechaolamine areas, the posterior area postrema and the trigeminal and dorsal root ganglia. Fibers were generally seen where cell bodies were observed. Very dense fiber bundles were noted in the septohypothalamic tract, the preoptic area, in the hypothalamus, the habenula and the thalamic periventricular nucleus, in the ventral hippocampus, parts of the reticular formation, in the locus coeruleus, the dorsal parabrachial area, the nucleus and tract of the spinal trigeminal area and the substantia gelatinosa, the superficial layers of the spinal cord and the posterior lobe of the pituitary. The localization of the GA-like immunoreactivity in the locus coeruleus suggests a partial coexistence with catecholaminergic neurons as well as a possible involvement of the GA-like peptide in a neuroregulatory role.     

Autoradiographic distribution of I-galanin binding sites in the rat central nervous system

Galanin (GAL) binding sites in coronal sections of the rat brain were demonstrated using autoradiographic methods. Scatchard analysis of ¹²⁵I-GAL binding to slide-mounted tissue sections revealed saturable binding to a single class of receptors with a Kd of approximately 0.2 nM. ¹²⁵I-GAL binding sites were demonstrated throughout the rat central nervous system. Dense binding was observed in the following areas: prefrontal cortex, the anterior nuclei of the olfactory bulb, several nuclei of the amygdaloid complex, the dorsal septal area, dorsal bed nucleus of the stria terminalis, the ventral pallidum, the internal medullary laminae of the thalamus, medial pretectal nucleus, nucleus of the medial optic tract, borderline area of the caudal spinal trigeminal nucleus adjacent to the spinal trigeminal tract, the substantia gelatinosa and the superficial layers of the dorsal spinal cord. Moderate binding was observed in the piriform, periamygdaloid, entorhinal, insular cortex and the subiculum, the nucleus accumbens, medial forebrain bundle, anterior hypothalamic, ventromedial, dorsal premamillary, lateral and periventricular thalamic nuclei, the subzona incerta, Forel's field H₁ and H₂, periventricular gray matter, medial and superficial gray strata of the superior colliculus, dorsal parts of the central gray, peripeduncular area, the interpeduncular nucleus, substantia nigra zona compacta, ventral tegmental area, the dorsal and ventral parabrachial and parvocellular reticular nuclei. The preponderance of GAL-binding in somatosensory as well as in limbic areas suggests a possible involvement of GAL in a variety of brain functions.     

Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity

Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are neurodegenerative disorders of the aging population characterized by the abnormal accumulation of alpha-synuclein (alpha-syn). Previous studies have suggested that excitotoxicity may contribute to neurodegeneration in these disorders, however the underlying mechanisms and their relationship to alpha-syn remain unclear. For this study we proposed that accumulation of alpha-syn might result in alterations in metabotropic glutamate receptors (mGluR), particularly mGluR5 which has been linked to deficits in murine models of PD. In this context, levels of mGluR5 were analyzed in the brains of PD and DLB human cases and alpha-syn transgenic (tg) mice and compared to age-matched, unimpaired controls, we report a 40% increase in the levels of mGluR5 and beta-arrestin immunoreactivity in the frontal cortex, hippocampus and putamen in DLB cases and in the putamen in PD cases. In the hippocampus, mGluR5 was more abundant in the CA3 region and co-localized with alpha-syn aggregates. Similarly, in the hippocampus and basal ganglia of alpha-syn tg mice, levels of mGluR5 were increased and mGluR5 and alpha-syn were co-localized and co-immunoprecipitated, suggesting that alpha-syn interferes with mGluR5 trafficking. The increased levels of mGluR5 were accompanied by a concomitant increase in the activation of downstream signaling components including ERK, Elk-1 and CREB. Consistent with the increased accumulation of alpha-syn and alterations in mGluR5 in cognitive- and motor-associated brain regions, these mice displayed impaired performance in the water maze and pole test, these behavioral alterations were reversed with the mGluR5 antagonist, MPEP. Taken together the results from study suggest that mGluR5 may directly interact with alpha-syn resulting in its over activation and that this over activation may contribute to excitotoxic cell death in select neuronal regions. These results highlight the therapeutic importance of mGluR5 antagonists in alpha-synucleinopathies.