Developmental profile of neuregulin receptor ErbB4 in postnatal rat cerebral cortex and hippocampus

We investigated the cellular and subcellular distributions of neuregulin tyrosine kinase receptor ErbB4 in the postnatal rat frontal cortex and hippocampus by light-, confocal- and electron-microscopic immunocytochemistry. At birth, ErbB4-immunoreactivity (ErbB4-IR) was prominent in the apical cytoplasm and dendrites of cortical plate neurons and hippocampal pyramidal cells. Throughout postnatal development and in adulthood, ErbB4-IR in both regions remained confined to the somatodendritic compartment of neurons, which increased in number to reach the adult pattern by the end of the first postnatal month (P30). At all ages examined, double-labeling experiments revealed that ErbB4-IR always co-localized with the neuronal marker neuronal nuclei (NeuN) and never with glial markers Nestin or glial fibrillary acidic protein (GFAP). Immunoperoxidase labeling at the ultrastructural level confirmed the exclusive localization of ErbB4-IR in somatodendrites, and notably in dendritic spines. Immunogold labeling showed preponderant ErbB4-IR in the cytoplasm, where it was associated with microtubules. Furthermore, ErbB4-IR was abundant in the nucleus of adult cortical and hippocampal neurons, suggesting a role for ErbB4 nuclear signaling in the brain beyond embryonic development. Taken together, these results show that ErbB4 is expressed by neuronal somatodendrites in cerebral cortex and hippocampus from birth to adulthood, and support a role for neuregulins in dendritic growth and plasticity.     

NGF在成年猴脑的分布

为了解NGF在成年猴脑的分布,采用免疫组化SP法对成年猴脑多个冠状位切片进行免疫组化反应。结果证明,NGF阳性反应神经元主要分布于大脑皮质Ⅲ、V层,小脑Purkinje细胞,海马,齿状回,纹状体,脑干网状结构等处。此外,在黑质、舌下神经核、迷走神经背核、前庭神经核、三叉神经核、疑核、下橄榄核也出现NGF阳性反应。在大脑和脑干还观察到NGF阳性胶质细胞。本实验结果表明,在成年猴脑的多个脑区有NGF表达,提示NGF可能涉及猴脑某些神经元及胶质细胞的生理过程。     

大鼠端脑内一氧化氮合酶阳性神经元的发育

目的研究大鼠胚胎时期及生后早期一氧化氮合酶（NOS）阳性神经元在端脑的分布,探讨一氧化氮（NO）在脑发育过程中的作用。方法应用还原型尼克酰胺腺嘌呤二核苷酸磷酸脱氢酶（NADPH-d）组织化学方法观察孕14d起至生后14d大鼠端脑内NOS阳性神经元的形态和分布。结果孕14d没有观察到阳性神经元。孕15d纹状体腹外侧已有NOS阳性表达。孕17d在大脑皮质、梨状皮质观察到NOS阳性神经元,但胞体小,树突短,且分支少。随着年龄的增长神经元的胞体数目增多、染色增强或维持一定的水平。到孕20d,NOS阳性神经元分布广泛,梨状皮质、纹状体腹外侧及终纹床核均有大量NOS阳性神经元,其胞体明显增大,树突分支复杂化,长度增加。在生后,除上述脑区的阳性神经元进一步发育分化,大脑皮质和纹状体的NOS阳性纤维相互编织成疏密不等的纤维网外,在胼胝体、海马也观察到NOS阳性神经元。到生后14d,NOS阳性神经元的分布模式总体上已与成年大鼠相似。结论NOS阳性神经元在端脑独特的表达模式提示NO在脑发育和成熟过程中扮演重要角色。     

Embryonic and postnatal development of the serotonergic raphe system and its target regions in 5-HT1A receptor deletion or overexpressing mouse mutants

The neurotransmitter 5-HT regulates early developmental processes in the CNS. In the present study we followed the embryonic and postnatal development of serotonergic raphe neurons and catecholaminergic target systems in the brain of 5-HT1A receptor knockout (KO) and overexpressing (OE) in comparison with wild-type (WT) mice from embryonic day (E) 12.5 to postnatal day (P) 15.5. Up to P15.5 no differences were apparent in the differentiation and distribution of serotonergic neurons in the raphe area as revealed by the equal number of serotonergic neurons in the dorsal raphe in all three genotypes. However, the establishment of serotonergic projections to the mesencephalic tegmentum and hypothalamus was delayed at E12.5 in KO and OE animals and projections to the cerebral cortex between E16.5 and E18.5 were delayed in OE mice. This delay was only transient and did not occur in other brain areas including septum, hippocampus and striatum. Moreover, OE mice caught up with WT and KO animals postnatally such that at P1.5 serotonergic innervation of the cortex was more extensive in the OE than in KO and WT mice. Tissue levels of 5-HT and of its main metabolite 5-hydroxyindoleacetic acid as well as 5-HT turnover were considerably higher in brains of OE mice and slightly elevated in KO mice in comparison with the WT, starting at E16.5 through P15.5. The initial differentiation of dopaminergic neurons and fibers in the substantia nigra at E12.5 was transiently delayed in KO and OE mice as compared with WT mice, but no abnormalities in noradrenergic development were apparent in later stages. The present data indicate that 5-HT1A receptor deficiency or overexpression is associated with increased 5-HT synthesis and turnover in the early postnatal period. However, they also show that effects of 5-HT1A KO or OE on the structural development of the serotonergic system are at best subtle and transient. They may nonetheless contribute to the establishment of increased or reduced anxiety-like behavior, respectively, in adult mice.     

Development of the ultrastructural features of somatostatin-immunoreactive neurons in the rat visual cortex

Summary The peroxidase-antiperoxidase immunocytochemical technique has been used to examine the development of the ultrastructural features of somatostatin (SRIF)-immunoreactive neurons in the visual cortex of the rat between embryonic day 17 and postnatal day 32. In the adult, stained neurons are distributed in layers II through VI and characterized by an abundance of cytoplasm containing a plethora of organelles, most conspicuous of which are cisternae of granular endoplasmic reticulum organized in parallel arrays.In embryonic tissue, SRIF-positive cells are present in the subplate and in the border between the cortical plate and marginal zone. These cells possess scanty cytoplasm containing a few organelles; synapses onto immunoreactive perikarya and dendrites are evident at this stage. At birth and in early postnatal life, labelled cells are confined to the subplate region. Already at this age a number of cells display signs of ultrastructural features which characterize them in adult life. At the end of the first postnatal week, SRIF-immunoreactive neurons span a considerable spectrum of maturity. At one extreme are a few cells with little cytoplasm surrounding a large nucleus and at the other are the majority of labelled neurons showing abundant cytoplasm including prominent arrays of granular endoplasmic reticulum.Labelled cells first appear in the more superficial layers at the beginning of the second postnatal week and attain a distribution similar to that observed in adult animals at the end of this week. At this time their ultrastructural features closely resemble those of their adult counterparts, and differences in cytoplasmic maturity between superficial and deep labelled cells are not evident. This suggests that the SRIF-producing neurons in the superficial layers begin to express this peptide after they complete their migration and have acquired their morphological features.Maturation proceeds during the third postnatal week; at this stage most cells acquire their mature nuclear and cytoplasmic features and an adult complement of synapses. However, a number of SRIF-immunoreactive cells contain a particularly prominent accumulation of cytoplasmic organelles and appear hypertrophic.     

Isolated catecholaminergic projections from substantia nigra and locus coeruleus to caudate,hippocampus and cerebral cortex formed by intraocular sequential double brain grafts

Summary Sequential intraocular grafting of defined areas from fetal rat brain to adult host rats was used to explore the possibility that such double grafts would become interconnected. Norepinephrine- containing neurons of the locus coeruleus were grafted together with either parietal cerebral cortex, hippocampus, or the caudate nucleus. Dopamine-containing neurons of the substantia nigra were transplanted together with either parietal cerebral cortex or the caudate nucleus. The brainstem grafts showed good survival and development in oculo, using both histochemical and electrophysiological criteria. Locus coeruleus neurons were found to innervate cerebral cortex, hippocampus, and the caudate nucleus. Substantia nigra neurons invaded cerebral cortex abundantly, with a terminal distribution typical of cortical DA terminals in situ. The innervation of the caudate nucleus from substantia nigra transplants was variable, but areas of dense confluent terminals were observed.We conclude that sequential brain grafting in oculo permits generation of isolated yet defined catecholaminergic projections, which are suitable for electrophysiological, pharmacological, and histochemical studies.     

Forebrain-specific promoter/enhancer D6 derived from the mouse Dach1 gene controls expression in neural stem cells

Drosophila dachshund is involved in development of eye and limbs and in the development of mushroom bodies, a brain structure required for learning and memory in flies. Its mouse homologue mDach1 is expressed in various embryonic tissues, including limbs, the eye, the dorsal spinal cord and the forebrain. We have isolated a forebrain-specific 2.5-kb enhancer element termed D6 from the mouse mDach1 gene and created D6-LacZ and D6-green fluorescent protein (GFP) reporter gene mouse lines. In embryonic stages, the D6 enhancer activity is first detected at embryonic day 10.5 in scattered cells of the outbuldging cortical vesicles. By embryonic day 12.5, D6 activity expands throughout the developing neocortex and the hippocampus. In the adult mouse brain, D6 enhancer is active in neurons of the cortical plate, in the CA1 layer of the hippocampus and in cells of the subventricular zone and the ventricular ependymal zone. Adult mice also show D6 activity in the olfactory bulb and in the mamillary nucleus. Cultured D6-positive cells, which were derived from embryonic and postnatal brains, show characteristics of neural stem cells. They form primary and secondary neurospheres that differentiate into neurons and astrocytes as examined by cell-specific markers.Our results show that D6 enhancer exerts highly tissue-specific activity in the neurons of the neocortex and hippocampus and in neural stem cells. Moreover, the fluorescence cell sorting of D6-GFP cells from embryonic and postnatal stages allows specific selection of primary neural progenitors and their analysis.     

Differential Expression of PTEN in Normal Adult Rat Brain and Upregulation of PTEN and p‐Akt in the Ischemic Cerebral Cortex

The tumor suppressor phosphatase and tensin homologue (PTEN) is a protein and lipid phosphatase. PTEN mutations have been associated with a large number of human cancers. To understand the physiological role of PTEN in the brain and its relationship to Akt in ischemic injury, we first investigated the localization of PTEN immunoreactivity in the brains of normal adult rats using immunohistochemistry. We then detected the modulation of PTEN and p‐Akt following transient global ischemia by Western blot and immunohistochemistry analyses. Our observation of normal brains showed that PTEN was heterogeneously distributed in the cytoplasm, nuclei, and processes in different regions. It was shown immunohistochemically that PTEN was distributed differentially in rat brain, with the highest levels in the anterior olfactory nucleus, cerebral cortex, amygdaloid nucleus, hippocampus, Purkinje's cells, and several nuclei in the basal ganglia, thalamus, midbrain, and pons. After global cerebral ischemia, PTEN and p‐Akt immunoreactivities were increased in the cerebral cortex. This was accompanied by the nuclear translocation of p‐Akt. Double‐labeling experiments revealed that PTEN and p‐Akt were most likely localized to neurons. These results suggest a role for PTEN in normal adult brain and that the PTEN/Akt pathway may be involved in neuronal survival or plasticity after ischemic injury. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

Nerve growth factor in the primate central nervous system: regional distribution and ontogeny

An enzyme immunoassay for nerve growth factor was developed to determine the regional distribution and ontogenic change in the macaque (Macaca fascicularis) CNS. The standard curve of mouse nerve growth factor paralleled the dilution curves of extracts from the primate CNS at the adult and pre-natal stages. Furthermore, the nerve growth factor immunoreactive material comigrated with mouse nerve growth factor by means of carboxy methyl cellulose chromatography. These findings suggest that the immunoreactive material extracted from the primate CNS is mouse nerve growth factor-like molecules. At the adult stage, the highest level of nerve growth factor was in the hippocampus, with relatively high levels also in the hypothalamus, the cerebral cortex, the amygdala, the basal nucleus of Meynert, the septal nucleus, the cerebellum and the caudate nucleus. No detectable amounts were observed in the spinal cord, the substantia nigra or the dentate nucleus. In addition to the CNS, the pituitary gland contained about four times the level found in the hippocampus. At embryonic day 120, a high level of nerve growth factor already existed in the occipital cortex (80% of the level at the adult stage) and in the hippocampus (70% of the level at the adult stage). Between embryonic day 120 and the newborn stage in the occipital cortex and between embryonic day 120 and postnatal day 60 in the hippocampus, nerve growth factor levels increased about 1.7-fold, and after that, they gradually decreased until the adult stage was reached. In contrast, in the cerebellum, the level was quite high during the pre-natal period and declined to one-third at postnatal day 60. The developmental changes in nerve growth factor and choline acetyltransferase activity in the hippocampus were well correlated (r = 0.963) between embryonic day 120 and postnatal day 60. Our studies reveal that nerve growth factor is present in the primate CNS. The high level of nerve growth factor during embryonic stages and the good correlation with choline acetyltransferase activity suggest a physiological role for nerve growth factor in the development of the primate CNS.     

Distribution of calbindin and parvalbumin in the developing somatosensory cortex and its primordium in the rat: an immunocytochemical study

Summary Immunocytochemical techniques were used to analyze the distribution of the calcium-binding proteins calbindin and parvalbumin during the pre- and postnatal development of the rat somatosensory cortex. Calbindin occurs in most early differentiated neurons that form the primordial plexiform layer at embryonic day 14. This expression in transient; during the perinatal period, calbindin becomes immunologically undetectable within the structures derived from the primordial plexiform layer, i.e., the prospective layers I and VIb. Immunoreactive neurons are also absent from adult layers I and VIb. Calbindin is also detected in a second population of neurons which, from embryonic day 18 onwards, distributes diffusely within the cortical plate. Some neurons of this population show morphological traits of immaturity, while others show complete dendritic arborization. The definitive pattern of distribution of calbindin-immunoreactive neurons is achieved by postnatal day 22. Infragranular layers contain intensely-immunoreactive cells whose numerical density decreases during postnatal development, whereas in supragranular layers similar neurons are interspersed among numerous faintly-stained neurons.Parvalbumin is detected for the first time at postnatal day 6, within a small group of neurons located in cortical layer V, and extends afterwards through the whole thickness of the cerebral cortex. At this same postnatal stage, groups of immunoreactivepuncta are also found in layer IV of the somatosensory cortex; these puncta increase in density progressively and, at embryonic day 13, immunoreactive cells appear also grouped at this level. At this postnatal age, parvalbumin immunostaining delineates the somatosensory map in cortical layer IV. From this stage to adulthood, the number of immunoreactive neurons increases in the whole thickness of the somatosensory cortex. Barrels in layer IV become less distinct as immunoreactive cells and processes invade the septa. Layer IV in the adult somatosensory cortex appears more densely populated by parvalbumin immunoreactive neurons and puncta than in the surrounding areas.     

神经黏附分子NB-3在转基因小鼠脑的发育表达

目的 检测NB-3在小鼠大脑组织中不同时期的表达情况. 方法采用带Lac Z基因的NB-3基因敲除的杂合子小鼠,分别取E12、E14、E16、E18、P0、P7、P14及成年小鼠的脑组织固定,采用X=gal染色方法检测Lac Z基因产物β-半乳糖苷酶的表达以显示NB-3的表达及定位.结果 1.NB-3在胚胎发育期间从E14开始有微弱的表达,后逐渐在侧脑室周围、皮层、丘脑、下丘脑及海马等部位表达.其中在皮层中的表达主要集中在Ⅱ,Ⅲ、Ⅴ层.2.NB-3在出生后小鼠大脑中的表达明显升高,在P7时表达最高,此后稍有下降直至成年.3.NB-3在成年小鼠大脑组织中的表达分布广泛.表达最强的部位分别是大脑皮层的Ⅱ/Ⅲ、Ⅴ层、梨状皮层、杏仁核周皮质、丘脑、下丘脑以及海马的CA1区等.结论 NB-3在发育和成体小鼠中枢神经系统中均有表达,且不同时期的表达量有所不同.提示NB-3在神经系统的发育过程中可能具有重要的作用.     

脑源性神经营养因子在成年猴脑的分布

采用免疫组织化学方法探讨了 BDNF在成年猴脑的分布。结果显示 ,脑源性神经营养因子阳性反应产物主要分布于下列结构 :大脑皮层 III～ V层的锥体细胞及突起 ;小脑皮质篮状细胞、Purkinje细胞、Golgi细胞及小脑顶核的神经元及其突起 ;海马各区的神经元、纤维和齿状核的颗粒细胞 ;尾状核、豆状核和室旁核部分神经元和纤维 ;脑干脑桥核、舌下神经核、迷走神经背核、前庭神经核、下橄榄核及网状结构的神经元及纤维或膨体。此外 ,在大、小脑的白质也可见到部分脑源性神经营养因子阳性胶质细胞。脑源性神经营养因子阳性反应产物广泛地分布于猴脑的多种区域和细胞 ,提示其功能可能涉及不同类型的神经元及可能的非神经细胞。本研究结果为探讨脑源性神经营养因子在成年猴脑的分布规律及其功能特点提供了有用的形态学依据。     

Ontogeny of the calcium binding protein parvalbumin in the rat nervous system

Summary In the adult rat brain, the calcium-binding protein parvalbumin is preferentially associated with spontaneously fast-firing, metabolically active neurons and coexists with gamma-amino-butyric acid (GABA) in cortical inhibitory interneurons. Whether this is so in developing neurons has not been explored. To this end, we have used parvalbumin immunohistochemistry to study expression of this protein in the rat nervous system during pre- and postnatal life. Our results indicate that parvalbumin first appears at embryonic day 13 in sensory system of the spinal cord, in the vestibular (VIII), the trigeminal (V) and the visuomotor (III, IV VI) systems, and develops rapidly during the following days. In these locations the expression of parvalbumin coincides with the beginning of physiological activity in nerve cells. In the gamma-aminobutyric acid (GABA)-containing interneurons of the cerebral cortex and the hippocampus, as well as in the Purkinje cells of the cerebellum, parvalbumin only appears postnatally. It lags behind the development of GABA-immunoreactivity by 1 to 2 weeks. The beginning of its expression, in the cerebellum at least, coincides with the arrival of excitatory synaptic input and the onset of spontaneous activity. Thus, during the development of the nervous system, the expression of parvalbumin is subordinate to the establishment of physiological activity.Abbreviations 3 oculomotor nucleus - 4 trochlear nucleus - 4n trochlear nerve - 6 abducens nucleus - 12 hypoglossal nucleus - 3n oculomotor nerve - 4V 4th ventricle - 5g trigeminal ganglion - 5n trigeminal nerve - 5mx trigeminal nerve, maxillary branch - 8c1 cochlear ganglion - 8g vestibular ganglion - 8n vestibular nerve - 10n vagal nerve - Amb ambiguus nucleus - CaBP calcium-binding protein - Ce cerebellum - ChP choroid plexus - cl cochlea - CPu caudate putamen - Cu cuneate nucleus - Cx cerebral cortex - df dorsal funiculus spinal cord - dr dorsal root spinal nerve - E15 embryonic day 15 of gestation - ECN external cuneate nucleus - Fr formatio reticularis - GABA gamma-amino-butyric acid - GAD glutamate decarboxylase - gl granular layer cerebellum - Gr gracile nucleus - Hip hippocampus - H heart - inc inferior colliculus - IOK inferior olive, kap cooy medial nucleus - Li liver - LMol lacunosum moleculare layer hippocampus - Lu lung - LV lateral ventricle - LVe(v) lateral vestibular nucleus (ventral) - LVe(d) lateral vestibular nucleus (dorsal) - me5 mesencephalic trigeminal tract - Me5 mesencephalic trigeminal nucleus - Mes mesencephalon - ml molecular layer cerebellum - MVe medial vestibular nucleus - Or oriens layer hippocampus - P 2 postnatal day 2 - Pu Purkinje-cell layer, cerebellum - Py pyramidal cell layer, hippocampus - R red nucleus - Rhom rhombencephalon - Rt reticular thalamic nucleus - sk skin - sn substantia nigra - spgl spinal ganglion - sp5 spinal trigeminal tract - SpVe spinal vestibular nucleus - Sp5I spinal trigeminal nucleus, interpolar - suc superior colliculus - SuVe superior vestibular nucleus - TBS tris-buffered saline - tch tactile hair sinus - ve vestibular epithelium - vb vertebral body - vh ventral horn spinal cord - VL ventrolateral thalamic nucleus - VP ventral pallidum - vr ventral root spinal nerve     

Development of the ultrastructural features of neuropeptide Y-immunoreactive neurons in the rat visual cortex

Summary Immunohistochemical studies have localized neuropeptide Y into a small population of non-pyramidal neurons in the mammalian cerebral cortex. In the rat, these cells are distributed in layers II–VI and are characterized at the ultrastructural level by an abundance of cytoplasm containing a plethora of organelles, most conspicuous of which are cisternae of granular endoplasmic reticulum stacked in parallel arrays. In the present study, we used electron microscopic immunocytochemistry to examine the ultrastructural development of neuropeptide Y-labelled neurons in the rat visual cortex from birth, when they first appear in this cortical area, until postnatal day 32. At birth and in the subsequent few days, neuropeptide Y neurons, found exclusively in layers V and VI, often show a deeply infolded nucleus and little cytoplasm containing few organelles. At the end of the first postnatal week, labelled cells are still restricted to layers V and VI and display immature features. However, at this stage, cells often show irregularly enlarged proximal dendrites filled with organelles. During the second postnatal week, neuropeptide Y-immunoreactive cell bodies appear for the first time in layers II and III, and at the end of this week they have a distribution similar to that observed in the adult. Labelled cells are overall more differentiated than at earlier ages showing some of the ultrastructural features which distinguish them in the adult. No differences in maturation are evident between immunoreactive neurons located in the superficial layers and those in the deep layers, suggesting that the neuropeptide Y neurons in the more superficial layers express the peptide after having completed their migration and have acquired their characteristic ultrastructural features. Maturation proceeds during the third postnatal week. At the end of this stage, neuropeptide Y-containing cells acquire their mature nuclear and cytoplasmic features and an adult complement of synapses.     

Shift of adenosine kinase expression from neurons to astrocytes during postnatal development suggests dual functionality of the enzyme

Adenosine is a potent modulator of excitatory neurotransmission, especially in seizure-prone regions such as the hippocampal formation. In adult brain ambient levels of adenosine are controlled by adenosine kinase (ADK), the major adenosine-metabolizing enzyme, expressed most strongly in astrocytes. Since ontogeny of the adenosine system is largely unknown, we investigated ADK expression and cellular localization during postnatal development of the mouse brain, using immunofluorescence staining with cell-type specific markers. At early postnatal stages ADK immunoreactivity was prominent in neurons, notably in cerebral cortex and hippocampus. Thereafter, as seen best in hippocampus, ADK gradually disappeared from neurons and appeared in newly developed nestin- and glial fibrillary acidic protein (GFAP)-positive astrocytes. Furthermore, the region-specific downregulation of neuronal ADK coincided with the onset of myelination, as visualized by myelin basic protein staining. After postnatal day 14 (P14), the transition from neuronal to astrocytic ADK expression was complete, except in a subset of neurons that retained ADK until adulthood in specific regions, such as striatum. Moreover, neuronal progenitors in the adult dentate gyrus lacked ADK. Finally, recordings of excitatory field potentials in acute slice preparations revealed a reduced adenosinergic inhibition in P14 hippocampus compared with adult. These findings suggest distinct roles for adenosine in the developing and adult brain. First, ADK expression in young neurons may provide a salvage pathway to utilize adenosine in nucleic acid synthesis, thus supporting differentiation and plasticity and influencing myelination; and second, adult ADK expression in astrocytes may offer a mechanism to regulate adenosine levels as a function of metabolic needs and synaptic activity, thus contributing to the differential resistance of young and adult animals to seizures.     

Tbr1影响大脑皮质发育及细胞分化与迁移

目的 探究Tbr1基因在大脑新皮质与海马发育过程中的功能。 方法 分别取胚胎165d、185d,出生后0d、3d、7d、14d昆明小鼠的脑组织,每个年龄点取材8～10 (共52) 只,常规固定脱水后石蜡切片,用免疫荧光检测小鼠大脑皮质、海马及齿状回神经细胞迁移与片层化发育过程中Tbr1的表达与分布情况。结果 1.在大脑皮质,Tbr1最早在皮质板广泛表达,随日龄的增加其表达逐渐向皮质板下层移动且最终定位于皮质的第Ⅵ层;2.相似地,齿状回处Tbr1在颗粒细胞层表达,P7之后其表达定位于颗粒细胞下层;3.根据其表达位置及组织发生规律,推测Tbr1阳性细胞即是皮质板内迁移中的新生神经元。 结论 Tbr1是影响小鼠大脑皮质发育及神经细胞迁移与分化的关键分子。作为新生神经元的标记物,Tbr1参与细胞分化与迁移以及大脑皮质片层化的形成过程。     

Noggin在大鼠中枢神经系统发育过程中的表达

目的 研究Noggin基因在大鼠中枢神经系统(CNS)发育过程中的表达。方法 地高辛标记的cRNA探针原位杂交组织化学技术。结果 ISHH结果显示，在胚胎期(E16)大鼠，noggin mRNA阳性细胞主要位于大脑皮质、海马、丘脑与下丘脑的部分核团。新生期(P1-P2)大鼠，noggin在大脑皮质与海马的表达均降低，而在丘脑与延脑的表达增强；生后1周(P1W)noggin在脑内的表达明显降低，生后2周noggin在脑内的表达开始升高，在大脑皮质与海马升高尤为明显。生后1个月，noggin表达继续升高，在额叶皮质、顶叶皮质、扣带皮质、梨状皮质及海马的齿状回可检测到强阳性信号；而在丘脑的侧核、网状核、腹内侧核与腹外侧核可见中等强度的阳性信号。此外，在下丘脑的室旁核和视上核亦可见密集深染的阳性神经元。生后3个月，noggin阳性细胞在脑内的表达开始降低；生后18个月，noggin表达降至最低，仅见散在的阳性神经元。此外，在不同发育期大鼠的脊髓亦未观察到noggin mRNA阳性细胞。结论 提示noggin基因参与大鼠生后CNS的发育。