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PubMedDate not supplied

Pediatric neuroblastic brain tumors containing abundant neuropil and true rosettes.

We have encountered a series of seven unusual neuroblastic pediatric central nervous system (CNS) neoplasms with a unique constellation of histologic, immunohistochemical, and ultrastructural features. The tumors presented in five girls and two boys, ages 1 to 3 years. In six cases the lesions involved the frontoparietal region, in one case the tectal plate. The tumors consisted of small to medium-sized, round to oval, hyperchromatic cells with poorly defined cytoplasmic borders. Cells were found in clusters and cords set in a paucicellular fibrillar neuropil matrix. Distinctive, virtually anuclear regions of neuropil were scattered throughout the lesions. True rosettes with well-formed central lumens often filled with granular debris were present, along with perivascular pseudorosettes and occasional Homer-Wright rosettes. Mitoses and apoptosis were frequent, but large regions of confluent necrosis were absent. Immunohistochemically, the neuropil-like areas as well as the perinuclear cytoplasm of many embryonal tumor cells were positive for synaptophysin and neurofilament protein. Ultrastructurally, the tumor cells showed microtubule-containing neuronal processes, some with neurosecretory granules. While the lesions were largely glial fibrillary acidic protein (GFAP) negative, there was focal GFAP positivity consistent with divergent differentiation in one case. The clinical outcome was poor, with five patients dead from their disease 5 to 14 months after initial presentation and one patient with recurrent disease 7 months after resection and chemotherapy. The final patient is alive without recurrent disease 30 months after initial presentation. These lesions present distinctive histological features within the group of primitive neuroectodermal tumors.

Apoptosis↗
PubMed1983

The Na+-K+ pump in neuropile glial cells of the medicinal leech.

The membrane potential of neuropile glial (NG) cells in the central nervous system of the medicinal leech and the K+ concentration in extracellular spaces (ECS) of the neuropile were measured under various experimental conditions to determine properties of a glial Na+-K+ pump. The ganglia were exposed to K+-free saline thereby loading the NG cells with intracellular Na+. Their membranes hyperpolarized transiently when the K+-free solution was replaced by a bathing medium with normal (= 4 mM) K+ concentration. The hyperpolarization increased in amplitude with time of exposure to K+ -free solution and could be abolished by ouabain or by replacing Na+ with Li+. The transient membrane hyperpolarization could not be attributed to K+ depletion in the ECS of the neuropile or to changes in membrane input conductance. In a (bathing) medium containing 5 X 10(-4) M ouabain, the K+ concentration in the ECS increased transiently, and the NG cell membrane depolarized rapidly. This short-term depolarization (duration 2-3 min) was followed by a second long-term depolarization (duration 15 min) of the NG cell membrane, which reached a steady-state 20 min after ouabain application. In a bathing medium with elevated external K+ concentrations, the amplitude of the membrane depolarization was enhanced by ouabain. This depolarizing ouabain effect was a result of K+ accumulation in the ECS. We conclude that the Na+-K+ pump does not contribute directly to the resting membrane potential of NG cells and is not directly involved in K+ homeostasis at the cellular level.

Animals↗
PubMed1990

Increases in mRNA for cytoskeletal proteins in the denervated neuropil of the dentate gyrus: an in situ hybridization study using riboprobes for beta-actin and beta-tubulin.

Following destruction of entorhinal cortical (EC) input to the dentate gyrus there is an increase in protein synthesis within the denervated dendritic laminae. The present study utilized in situ hybridization to determine whether there were increases in the messenger RNAs (mRNAs) for beta-actin and beta-tubulin within the denervated neuropil of the dentate gyrus during the time of increased protein synthesis. Animals were prepared for in situ hybridization 2-21 days after a unilateral lesion of the EC. Brain sections were hybridized with either 3H or 35S-labeled riboprobes prepared from chick beta-actin and chick beta-tubulin mRNA. Analysis of light microscopic autoradiograms revealed increases in the mRNAs for beta-actin and beta-tubulin within the denervated neuropil between 6 and 8 days postlesion when compared to the intact dentate gyrus of the contralateral side. Labeling over the granule cell body layer was comparable on the two sides for both probes. Increases in both mRNAs were also observed in the scar tissue at the lesion site. These results suggest that local protein synthesis within the denervated neuropil of the dentate gyrus involves, in part, an increase in the production of actin and tubulin.

Actins↗
PubMed1983

Increases in protein-precursor incorporation in the denervated neuropil of the dentate gyrus during reinnervation.

Cellular metabolic events accompanying postlesion synaptogenesis in the hippocampus were studied by analyzing incorporation of protein precursor ([3H]leucine) in the dentate gyrus. Adult rats were injected intravenously with [3H]leucine at periods from 2 to 60 days following unilateral destruction of the entorhinal cortex, and were killed 30 min later. Precursor incorporation was quantified autoradiographically by counting silver grains over the cell bodies and dendrites of dentate granule cells ipsi- and contralateral to the lesion. The relative grain density was increased over the denervated portion of the neuropil at 6-12 days postlesion, corresponding to the early phase of terminal proliferation and reactive synaptogenesis. Whereas incorporation was increased over the denervated neuropil, the availability of [3H]leucine was decreased relative to the contralateral side in autoradiographic preparations designed to reveal the concentration of the unincorporated 3H-labeled precursor and its diffusible degradation products. Silver grains were not selectively associated with glial cells bodies or vascular elements, but rather were distributed diffusely throughout the neuropil. Increases in grain density over the denervated zone were observed when animals were killed 8 min after the leucine injection, suggesting that the increases were not due solely to rapid transport from granule cell bodies to dendrites. We propose that an increased incorporation of protein precursor occurs primarily within the denervated dendrites of granule cells during the early phase of reinnervation, and that protein synthetic activity in these cells might be involved in the process of reinnervation.

Animals↗
PubMed1989

Effect of retinal impulse blockage on cytochrome oxidase-rich zones in the macaque striate cortex: II. Quantitative electron-microscopic (EM) analysis of neuropil.

Unilateral retinal impulse blockage with tetrodotoxin (TTX) induces reversible shrinkage and decreased cytochrome oxidase (CO) activity in alternate rows of supragranular, CO-rich puffs in the adult macaque striate cortex (Wong-Riley & Carroll, 1984b: Carroll & Wong-Riley, 1987). The present study extended the findings to the electron-microscopic (EM) level to determine if various neuropil profiles in control puffs exhibit heterogeneous levels of CO activity, and whether specific processes were more susceptible to intravitreal TTX than others. Within the neuropil of control puffs, 60% of the total mitochondrial population resided in dendrites, and the majority of dendritic mitochondria were highly reactive for CO. Axon terminals forming symmetrical synapses also contained darkly reactive mitochondria, whereas those forming asymmetrical synapses possessed very few and mainly lightly reactive mitochondria. Unmyelinated axon trunks, myelinated axons, and glia all exhibited low levels of CO activity. Synaptic count revealed a 3:1 ratio of asymmetrical to symmetrical synapses. Intravitreal TTX for 2-4 weeks adversely affects dendrites and symmetrical terminals much more so than other neuropil processes. There was a general decrease in darkly and moderately reactive mitochondria and an increase in lightly reactive mitochondria throughout the puffs, especially in dendrites. This indicates that afferent blockade is more detrimental to processes of higher metabolic activity. Changes also differed between central and peripheral regions of puffs, and indications of axonal and synaptic reorganization were more evident in the latter. Thus, stabilization of neuronal structure and synapses appears to be activity-dependent even in the adult. A working model of these metabolic and morphological responses to chronic TTX is proposed.

Animals↗
PubMedDate not supplied

Neuropil threads occur in dendrites of tangle-bearing nerve cells.

Transparent Golgi preparations counterstained for Alzheimer's neurofibrillary changes rendered possible the demonstration of neuropil threads in defined cellular processes. Only dendrites of tangle-bearing cortical nerve cells were found to contain neuropil threads. Processes of glial cells as well as axons present in the material were devoid of neuropil threads.

Alzheimer Disease↗
PubMed1993

Glucose utilization rates in single neurons and neuropil determined by injecting nontracer amounts of 2-deoxyglucose.

A nontracer amount of 2-deoxyglucose (DG) was intravenously injected into rats, which were frozen 2 and 4 min later in liquid nitrogen. The freeze-dried samples of cell bodies of anterior horn cells, dorsal root ganglion cells, and cerebellar Purkinje cells, as well as the neuropil adjacent to anterior horn cell bodies, were prepared. Their contents of glucose, glucose 6-phosphate, DG, and 2-deoxyglucose 6-phosphate were microassayed using an enzymatic amplification reaction. NADP cycling. Based on the resulting data and theoretical equations previously described, glucose utilization rate (GUR) and apparent distribution volumes (DVs) of glucose and DG were determined. Anterior horn cell bodies had the highest GUR and their neuropil the lowest, although apparent DVs of glucose and DG were similar in both. This indicates that the glucose supply was equally balanced in all, but that the cell bodies had higher functional activity supported by hexokinase (and other enzymes) related to their energy demands. Dorsal root ganglion cells showed the lowest 2-deoxyglucose 6-phosphate formation rate, but their GUR was slightly higher than that of neuropil because of their markedly large DV of glucose, thus demonstrating that the abundant glucose supply supports the neuronal function. Purkinje cells indicated GUR and apparent DVs similar to molecular and granular layers.

Animals↗
PubMedDate not supplied

Quantitative assessment of the synaptophysin immuno-reactivity of the cortical neuropil in various neurodegenerative disorders with dementia.

It has remained a matter of debate until now whether amyloid and tangle pathology may be regarded as the main causes of the dementia in Alzheimer's disease (AD) or only as markers of the disease. In the present study we examined the synaptophysin immunoreactivity of the cortical neuropil as a measure of its synapse density, in 17 cases of AD, 1 case with a 10-month episode of dementia and cortical amyloid deposition, 5 cases of Huntington's disease (HD) with dementia, 11 cases of parkinsonism (PD), 5 with dementia (PD-D) and 16 controls. The immunoreactivity was assessed in two layers (molecular, pyramidal) of three regions (frontal, occipital, hippocampus) by means of automated black-and-white image analysis. In AD we found a rather diffuse reduction of the cortical synaptophysin expression of up to 26.5% (mean 11%) of the controls. No correlation was found between synaptophysin expressivity and age either in AD or in the controls. Univariate analyses revealed only a very weak negative correlation between the density of beta A4-immunoreactive cortical plaques and the intensity of the synaptophysin staining, while in a multivariate analysis the plaque density did not show any impact on the latter. In HD a reduction of the synaptophysin immunoreactivity of the cortical neuropil was also found (mean 10.4%), with a predominance in the pyramidal layer of the neocortex. The same was true for PD (5.3%) and PD-D (8.2%). Our results support the view that loss of synapses in the cortical neuropil may be a significant factor for the development of organic dementia, while the amyloid pathology in AD is more likely a marker of the disease.

Adult↗
PubMed1980

Extracellular potassium in neuropile and nerve cell body region of the leech central nervous system.

Potassium-sensitive double-barrelled microelectrodes were used to measure the potassium content of extracellular spaces in leech ganglia, both intact and with the ganglion capsule opened. When the ganglion capsule was opened, the extracellular concentrations of potassium in the ganglion were similar to that of the bathing medium (4 mM). With intact ganglia the extracellular potassium concentration in the neuropile averaged 6.3 +/- 0.7 mM and in the nerve cell body region 5.8 +/- 0.6 mM. The potential measured in these parts of the ganglion was between +2 and -8 mV, averaging -1.9 mV. The change of potassium concentration in the extracellular spaces following increase or decrease in the concentration of potassium ions in the bath declined exponentially. This rate of change, which would be expected of a first-order diffusion process, was found in both the neuropile and the nerve cell body region. In a medium containing 5 x 10(-4) M ouabain, the potassium concentration in both parts of the ganglion increased transiently by an average of 3.8 +/- 1.0 mM in the neuropile and 1.2 +/- 0.4 mM in the nerve cell body region. Negatively charged polyelectrolytes in extracellular spaces of leech ganglia could affect the distribution of potassium ions to give a Donnan distribution. It is also possible, that the endothelial layer influences the extracellular potassium concentration in a ganglion under resting conditions.

Animals↗
PubMed1999

Neuropil pattern formation and regulation of cell adhesion molecules in Drosophila optic lobe development depend on synaptobrevin.

To investigate a possible involvement of synaptic machinery in Drosophila visual system development, we studied the effects of a loss of function of neuronal synaptobrevin, a protein required for synaptic vesicle release. Expression of tetanus toxin light chain (which cleaves neuronal synaptobrevin) and genetic mosaics were used to analyze neuropil pattern formation and levels of selected neural adhesion molecules in the optic lobe. We show that targeted toxin expression in the developing optic lobe results in disturbances of the columnar organization of visual neuropils and of photoreceptor terminal morphology. IrreC-rst immunoreactivity in neuropils is increased after widespread expression of toxin. In photoreceptors, targeted toxin expression results in increased Fasciclin II and chaoptin but not IrreC-rst immunoreactivity. Axonal pathfinding and programmed cell death are not affected. In genetic mosaics, patches of photoreceptors that lack neuronal synaptobrevin exhibit the same phenotypes observed after photoreceptor-specific toxin expression. Our results demonstrate the requirement of neuronal synaptobrevin for regulation of cell adhesion molecules and development of the fine structure of the optic lobe. A possible causal link to fine-tuning processes that may include synaptic plasticity in the development of the Drosophila CNS is discussed.

Animals↗
PubMed2000

Synaptic neuropil in nerves of the crustacean stomatogastric nervous system: an immunocytochemical and electron microscopical study.

Patches of peptide-immunoreactive varicosities have been found in nerves of the stomatogastric nervous system (STNS) of decapod crustaceans. In the present study, these patches were examined in detail in the stomatogastric nerve (stn) and in the superior oesophageal nerve (son) of the crayfish Cherax destructor by using whole-mount immunocytochemical techniques combined with confocal microscopy and, in addition, electron microscopy. Double-labeling experiments with antibodies generated against the peptides allatostatin, FMRFamide and proctolin, combined with an antibody generated against the small vesicle protein synapsin, suggest that each patch contains small synaptic vesicles in addition to all three peptides. The neuropil regions of the ganglia of the STNS were also strongly stained by the synapsin antibody. Synapsin-like immunoreactivity was also studied in the crab Cancer pagurus and the lobster Homarus americanus. A similar pattern of staining was found for all three species, but the distribution within the stn varied. In H. americanus, a lightly stained weblike structure was found on the surface of nerves including the inferior oesophageal nerve, the son, and the anterior stn. By using electron microscopy, synapses were found in the core of the stn-son junction of C. destructor, in the same region where the synapsin-like and the peptide staining was localized. In addition, putative neurohemal release sites were found in the peripheral sheath of the stn. The presynaptic profiles found in the core of the stn seem to correspond to the types of presynaptic profiles found in the neuropil of the stomatogastric ganglion. These findings demonstrate that synaptic neuropil is present in the nerves of the STNS of a decapod crustacean.

Animals↗
PubMed1990

[The ultrastructure of the inferior olivary complex in ground squirrels (Citellus citellus L.). The neuropil. Age-related changes in the axons].

The morphological characteristics of axon terminals among a neuropil in the lower olivary complex of ground squirrels at various ages were studied by an electron microscope. The presynaptic part of the chemical synapses in the glomerular or outside glomerular position among the neuropil pf this nuclear complex were axon terminals and terminals "en passant". These axon elements participate in the formation of crash-like synapses with somatic, dendrite prickles, but also with dendrite adjuncts in the formation of complex synaptic connections. A considerable part of myelin axons and axon terminal were changed in old ground squirrels during all seasons. There were two varieties: 1. axon elements with preserved sizes and dense bodies, myelin-like figures, a large number of mitochondria and glycogen granules were found among normal organoids. 2. myelin and amyelin "spheroids" with various sizes and inner structure. The changes axon elements of the neuropil in the inferior olivary complex of ground squirrels at various ages during all seasons are physiological probably connected with the process of aging.

Aging↗
PubMed1985

Ultrastructural morphology of the neuropile of the cerebral ganglion of Moniliformis moniliformis (Acanthocephala).

The cerebral ganglion of Moniliformis moniliformis consists of an outer single layer of cell bodies and an inner core of neuropile occupied by cellular processes. Morphological characteristics of 5 types of cellular processes have been described. Most of the processes in the neuropile were of large size, although sites containing numerous small processes (neurites) were also observed. Small processes in the neuropile were the sites of synaptic interaction. The majority of presynaptic membranes were well defined by the presence of electron-dense material at the inner leaflet, while postsynaptic membranes appeared to lack marked postsynaptic density. Round or flattened lucent vesicles were concentrated around the presynaptic membranes. Electron-dense and dense-cored vesicles were usually separated from the clear vesicles and situated at some distance from synaptic sites.

Acanthocephala↗
PubMed1998

Frontotemporal dementia: neuropil spheroids and presynaptic terminal degeneration.

We compared the neuropathological changes of 6 patients with clinically diagnosed lobar dementia. In the 4 patients with histopathology consistent with frontotemporal dementia (FTD), moderate neuronal loss contrasted with marked cortical and subcortical gliosis. We found silver-positive, carbohydrate-rich, spheroidal enlargements of presynaptic terminals within the neuropil of specific central nervous system regions. The spheroids were immunopositive for the cytoskeletal proteins tau, the high molecular weight neurofilament subunit (NF-H), and beta-tubulin. No abnormal tau phosphorylation and only rare ubiquitin immunoreactivity were detected in these structures. Carbohydrate modifications, including advanced glycation end products within the spheroid matrix, were confirmed by lectin binding, and by anti-pentosidine immunoreactivity, an indicator of oxidative stress. Ultrastructurally, the spheroids consisted of unmyelinated, membrane-enclosed structures filled with randomly arrayed pairs of filaments, approximately 8 to 10 nm in diameter, that were sparsely labeled with antibodies to unmodified tau (T14) and NF-H. Despite clinical overlap, the central nervous systems of our FTD patients are distinguishable from those of other patients with other lobar dementias, including Pick's disease and corticobasal degeneration, by the absence of abnormally phosphorylated neuronal or glial tau inclusions. The neuropil spheroids are dystrophic changes of certain selectively vulnerable presynaptic terminals, suggesting a retrograde degenerative process in FTD.

Adult↗
PubMed2006

Restricted distribution of D-unit-rich chondroitin sulfate carbohydrate chains in the neuropil encircling the optic tract and on a subset of retinal axons in chick embryos.

To obtain basic information about the structural diversity and functional specificity of chondroitin sulfates (CSs) in the formation of the retinotectal pathway in chick embryos, the distribution of CSs around the optic tract was investigated by using anti-CS monoclonal antibodies with different specificities. The CSs are unbranched polymers composed of repeating disaccharide units of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc). The disaccharide units are classified into O-, A-, C-, D-, and E-units based on the position(s) of the added sulfate group(s). The MO-225 monoclonal antibody recognizes CSs that are rich in the D-unit [GlcA(2S)beta1-3GalNAc(6S)]; the MO-225 epitopes were distributed in the diencephalotelencephalic boundary and the neuropil encircling the optic tract. In addition, they were distributed on membrane surfaces of the retinal axons running in an interface layer in contact with the neuropil encircling the optic tract. The results suggest that D-unit-rich CSs are involved in delimiting the border of the optic tract and in the chronological sorting of the retinal axons.

Animals↗
PubMed2006

Histological and cytological study of the bed nuclei of the stria terminalis in adult rat. II. Oval nucleus: extrinsic inputs, cell types, neuropil, and neuronal modules.

The oval nucleus (Ov) of the bed nuclei of the stria terminalis was studied in adult rats. The Ov is composed of 11 neuron types distributed into a shell and a core domain. The stria terminalis, internal capsule, ventral amygdaloid pathway, and medial forebrain bundle are the main sources of afferents to the neuropil of the Ov. The nucleus shell contains abundant intrinsic neurons possibly connected among themselves and with the core by centripetal axon collaterals. Series of intrinsic neurons in the shell, linked with both short-axon and projecting neurons in the core, suggest a centripetal control of projecting neurons. In situ hybidization for vesicular glutamate transporter (VGlu) and glutamic acid decarboxylase (GAD) show numerous GAD-synthesizing neurons and an absence of VGlu-synthesizing neurons. In the electron microscope, the neuropil of the Ov contains axospinous, axoshaft, axosomatic, mixed (i.e., chemical-electrical), and axoaxonic synapses, in order of frequency. Synaptic boutons in apposition with the initial segment, represent an additional axoaxonic interaction. Further neural synchronization of the Ov occurs via gap junctions between somata, soma-dendrite, and possibly by apposition between axon terminals. The putative inputs from the major tracts of the forebrain coupled with the cytological organization of the Ov make it one of the most complex structures of the mammalian brain.

Animals↗
PubMed2004

Decreasing glutamate buffering capacity triggers oxidative stress and neuropil degeneration in the Drosophila brain.

L-glutamate is both the major brain excitatory neurotransmitter and a potent neurotoxin in mammals. Glutamate excitotoxicity is partly responsible for cerebral traumas evoked by ischemia and has been implicated in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). In contrast, very little is known about the function or potential toxicity of glutamate in the insect brain. Here, we show that decreasing glutamate buffering capacity is neurotoxic in Drosophila. We found that the only Drosophila high-affinity glutamate transporter, dEAAT1, is selectively addressed to glial extensions that project ubiquitously through the neuropil close to synaptic areas. Inactivation of dEAAT1 by RNA interference led to characteristic behavior deficits that were significantly rescued by expression of the human glutamate transporter hEAAT2 or the administration in food of riluzole, an anti-excitotoxic agent used in the clinic for human ALS patients. Signs of oxidative stress included hypersensitivity to the free radical generator paraquat and rescue by the antioxidant melatonin. Inactivation of dEAAT1 also resulted in shortened lifespan and marked brain neuropil degeneration characterized by widespread microvacuolization and swollen mitochondria. This suggests that the dEAAT1-deficient fly provides a powerful genetic model system for molecular analysis of glutamate-mediated neurodegeneration.

Animals↗
PubMed2005

Genetic dissection of trophic interactions in the larval optic neuropil of Drosophila melanogaster.

The larval visual system of Drosophila melanogaster consists of two bilateral clusters of 12 photoreceptors, which express Rhodopsin 5 and 6 (Rh5 and Rh6) in a non-overlapping manner. These neurons send their axons in a fascicle, the larval optic nerve (LON), which terminates in the larval optic neuropil. The LON is required for the development of a serotonergic arborization originating in the central brain and for the development of the dendritic tree of the circadian pacemakers, the small ventral lateral neurons (LNv) [Malpel, S., Klarsfeld, A., Rouyer, F., 2002. Larval optic nerve and adult extra-retinal photoreceptors sequentially associate with clock neurons during Drosophila brain development. Development 129, 1443-1453; Mukhopadhyay, M., Campos, A.R., 1995. The larval optic nerve is required for the development of an identified serotonergic arborization in Drosophila melanogaster. Dev. Biol., 169, 629-643]. Here, we show that both Rh5- and Rh6-expressing fibers overlap equally with the 5-HT arborization and that it, in turn, also contacts the dendritic tree of the LNv. The experiments described here aimed at determining whether Rh5- or Rh6-expressing fibers, as well as the LNv, influence the development of this serotonergic arborization. We conclude that Rh6-expressing fibers play a unique role in providing a signal required for the outgrowth and branching of the serotonergic arborization. Moreover, the innervation of the larval optic neuropil by the 5-HT arborization depends on intact Rac function. A possible role for these serotonergic processes in modulating the larval circadian rhythmicity and photoreceptor function is discussed.

Animals↗