Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “neuron”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1992

Cholinergic deafferentation prevents delayed neuronal death of the hippocampal CA1 pyramidal neurons after transient forebrain ischaemia.

The relation between CA1 neurons, fimbria-fornix and cholinergic neurons of the basal forebrain was examined with the aid of Acetylcholine esterase (AChE) staining, Woelcke's staining and immunohistochemistry of Choline-acetyl transferase (ChAT). The transected side of the hippocampus was poorly stained by AChE two weeks after the transection, when the ipsilateral medial septum ChAT-positive neurons were reduced, but showed good recovery with AChE six weeks later. Nerve growth factor (NGF) was added at a dose of 10 micrograms/100 microliters immediately after the aspiration, and after that once per week with cisternal puncture. As a result, ipsilateral medial septum ChAT-positive neurons were preserved, but cross innervation with relation to hypertrophy of the cholinergic neurons was not detectable even six weeks after the transection. Furthermore, delayed CA1 neuronal death on the transected side of the hippocampus following occlusion of four vessels for 30 minutes was not detectable two weeks after the operation, although neuronal density was reduced after six weeks. The density of neurons on the transected side of the hippocampus in the CA1 subfield with treated NGF had not decreased significantly six weeks later. Therefore, we suspect that the input from cholinergic fibres must be transported to the hippocampal pyramidal neurons responding to NGF, and it was confirmed that cholinergic deafferentation prevents the delayed neuronal death of CA1 pyramidal neurons during transient ischaemia.

Afferent Pathways↗
PubMed1991

The Relationship of Microglial Cells to Dying Neurons During Natural Neuronal Cell Death and Axotomy-induced Degeneration of the Rat Retina.

The interactions between dying neurons and phagocytotic cells within the developing and injured retina remain controversial. The present work explored the role of microglia and investigated whether so-called resident microglial cells are permanently responsible for removing cell debris whenever it is produced. As a first goal, I characterized some quantitative and morphometric features of the small ipsilateral retinocollicular projections and analysed the permanent function of phagocytosing microglia with these projections as a paradigm. To achieve this, I combined the fluorescent dyes Dil and 4Di-10ASP, both of which persist in the labelled ganglion cells after injection into the superior colliculus (SC), and retrograde labelling. After neuronal degradation, the dyes accompany the degradation products, become interiorized and then persist within the phagocytosing microglia. Consequently, early labelling of microglial cells can be assessed by injecting one dye into the SC during the first postnatal day of life, that is, prior to advanced natural neuronal cell death. Labelling of the remaining ipsilaterally projecting neurons with the second dye following intraorbital axotomy in adulthood and during subsequent neuronal death would therefore result in double labelling of some microglial cells, if these were involved in phagocytosis during both the natural and the induced phases of neuronal degradation. The ganglion cells which survived natural neuronal cell death remained fluorescent for 3 months after labelling with either dye on the day of the animal's birth, indicating that both fluorescent probes persisted within neurons. Quantitatively, 1770+/-220 ganglion cells/mm2 were labelled within the contralateral retina and a total population of 1442+/-120 cells/retina were observed within the periphery of the inferior/temporal quadrant of the ipsilateral retina. A smaller, ipsilateral projection of 150+/-24 cells/retina was uniformly scattered throughout the rest of the retinal surface. Transient projections of ganglion cells to either the contralateral or the ipsilateral colliculi and death of labelled ganglion cells during the first postnatal days resulted in labelling of 210+/-36 microglial cells/mm2 within the contralateral retina and a total number of 800+/-120 cells/retina within the inferior/temporal and 200+/-22 cells/retina within the rest of the retina. These labelled microglial cells were observed in adulthood and indicated that after taking away the neuronal cell debris they persisted within the retinal tissue. The small number of prelabelled ganglion cells which formed persistent ipsilateral projections until adulthood were axotomized by transecting the optic nerve, and resulted in additional labelling of microglial cells with the second fluorescent dye as well. Double-labelled microglia were observed within the inferior/temporal quadrant (3500+/-240 cells/retina) and to a lesser extent (340+/-40 cells/retina) scattered over the entire retinal surface. The chronotopological sequence of microglial labelling paralleled that of ganglion cell degeneration. Injection of protease inhibitors into the vitreous body during optic nerve transection retarded retrograde glial cell degeneration, probably by blocking microglial proteases. The results directly proved that the same microglial cells which remove neuronal cell debris in the postnatal retina were reactivated later in life to proteolytically degrade and then phagocytose neurons which had altered because of the axotomy.

Journal Article↗
PubMed1995

Effect of pre- or postnatal exposure to ethanol on the total number of neurons in the principal sensory nucleus of the trigeminal nerve: cell proliferation and neuronal death.

Early exposure to ethanol reduces the number of neurons in many CNS structures in vivo. The present study determined whether such reductions are caused by the death of neurons. Three groups of ethanol-treated rats were prepared: those exposed to ethanol from gestational day (G) 11 to G19 (during the period of neuronal generation and migration), from postnatal day (P) 4 to P12 (during the period of synaptogenesis), or from P31 to P39 [after the mature structure and function of neurons in the principal sensory nucleus (PSN) of the trigeminal nerve was established]. During these times, pregnant dams or pups were fed a liquid ethanol-containing diet that produced peak blood ethanol concentrations of 137-157 mg/dl. The number of PSN neurons in mature rats exposed to ethanol pre- or postnatally was determined using stereological procedures. The number of PSN neurons was also calculated for rats pair-fed an isocaloric liquid control diet or fed chow and water and libitum. The volume of the PSN was not affected by pre- or postnatal ethanol exposure. The number of PSN neurons, however, was significantly affected by ethanol exposure in a time-dependent manner. Prenatal exposure lead to a 27.1% decrease in neuronal number. Early postnatal exposure led to a smaller decrease (-15.1%), and late postnatal exposure had no affect on the number of PSN neurons. These data show not only that ethanol directly depresses the proliferation of neuronal precursors, but also that ethanol causes the death of neurons during the period of synaptogenesis.

Animals↗
PubMed2006

Clinically undetected motor neuron disease in pathologically proven frontotemporal lobar degeneration with motor neuron disease.

BACKGROUND: Frontotemporal lobar degeneration with motor neuron disease (FTLD-MND) is a pathological entity characterized by motor neuron degeneration and frontotemporal lobar degeneration. The ability to detect the clinical signs of dementia and motor neuron disease in pathologically confirmed FTLD-MND has not been assessed. OBJECTIVES: To determine if all cases of pathologically confirmed FTLD-MND have clinical evidence of frontotemporal dementia and motor neuron disease, and to determine the possible reasons for misdiagnosis. METHOD: Review of historical records and semiquantitative analysis of the motor and extramotor pathological findings of all cases of pathologically confirmed FTLD-MND. RESULTS: From a total of 17 cases of pathologically confirmed FTLD-MND, all had clinical evidence of frontotemporal dementia, while only 10 (59%) had clinical evidence of motor neuron disease. Semiquantitative analysis of motor and extramotor pathological findings revealed a spectrum of pathological changes underlying FTLD-MND. Hippocampal sclerosis, predominantly of the subiculum, was a significantly more frequent occurrence in the cases without clinical evidence of motor neuron disease (P<.01). In addition, neuronal loss, gliosis, and corticospinal tract degeneration were less severe in the other 3 cases without clinical evidence of motor neuron disease. CONCLUSIONS: Clinical diagnostic sensitivity for the elements of FTLD-MND is modest and may be affected by the fact that FTLD-MND represents a spectrum of pathological findings, rather than a single homogeneous entity. Detection of signs of clinical motor neuron disease is also difficult when motor neuron degeneration is mild and in patients with hippocampal sclerosis.

Adult↗
PubMed1992

Phenotypic plasticity of avian embryonic sympathetic neurons grown in a chemically defined medium: direct evidence for noradrenergic and cholinergic properties in the same neurons.

Avian embryonic sympathetic ganglia possess both catecholaminergic and cholinergic features and can synthesize noradrenaline (NAd) and acetylcholine (ACh) simultaneously. In the present study we sought to determine (1) whether or not this coproduction of NAd and ACh corresponds to the existence of two non-overlapping populations, and (2) to what extent the levels of synthesis are influenced by non-neuronal ganglion cells. We have focused on the correlation between the immunocytochemically demonstrable presence of the noradrenergic and cholinergic enzymes tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT), respectively, and the synthesis of the corresponding neurotransmitters in embryonic quail sympathetic neuronal and non-neuronal cells purified by fluorescence-activated cell sorting. We show that (1) freshly sorted neurons synthesize both NAd and ACh, whereas non-neuronal cells produce neither; (2) the overwhelming majority of the sympathetic neurons display TH immunoreactivity; (3) about half of the TH-positive neurons are recognized by an anti-ChAT antibody in an artificial medium that selectively enhances synthesis and/or accumulation of ACh; (4) the non-neuronal cells are important for survival of the neurons and potentiate their synthesis of ACh in this medium, and (5) finally, we present evidence that expression of TH in noradrenergic neurons and in small intensely fluorescent cells of sympathetic ganglia is differentially regulated.

Animals↗
PubMed1985

Ring neuron control of columellar motor neurons during egg-laying behavior in the pond snail.

Egg-laying in Lymnaea is characterized by the stereotyped egg-laying behavior (ELB), composed of foot contractions and shell movements. Egg-laying can be induced by a clean water stimulus, that triggers a discharge of the neuroendocrine caudo-dorsal cells (CDCs), which release the ovulation hormone into the blood. A part of the behavior is lost when egg-laying is triggered by hormone injection, indicating that during natural stimulus-induced or spontaneous egg-laying this part (the first phase) may be controlled by neuronal events in the CNS triggered by (a) factor(s) not released to the blood. The authors have identified an unpaired neuron, the ring neuron, that is excited during an in vitro afterdischarge of the CDCs, and which, by its numerous axonal branches in the pedal ganglia, modulates motorneurons of the columellar muscle, which controls shell movements. These motor-neurons, identified as such in reduced preparations by 1 for 1 muscle potentials and elements in the connecting nerve, all receive either excitatory or inhibitory input from the ring neuron, as well as from an unknown neuron which has common input of the ring neuron and the motorneurons. The action of the CDCs on the ring neuron cannot be mimicked by the ovulation hormone, and we therefore conclude that the first part of the ELB is probably caused by a nonhormonal local action of the CDCs on the ring neuron and possibly the common input neuron.

Animals↗
PubMed1994

Axotomy induces intranuclear immunolocalization of neuron-specific enolase in facial and hypoglossal neurons of the rat.

Neuron-specific enolase as an enzyme of the glycolytic pathway is localized in the cytoplasm of nerve cells, but not in the cell nucleus. We have applied immunocytochemistry with 1:64,000 polyclonal anti-rat neuron-specific enolase to the brainstem of male and female adult Wistar rats following: (a) transection of the facial nerve with immediate microsurgical nerve suture (facial-facial anastomosis), (b) transection of the hypoglossal nerve with immediate suture (hypoglossal-hypoglossal anastomosis) and (c) transection of the facial and hypoglossal nerve with immediate suture of the proximal hypoglossal to the distal facial nerve stump (hypoglossal-facial anastomosis). Studying the intracellular immunolocalization of neuron-specific enolase in neurons of the facial and hypoglossal nucleus we detected that (1) in normal rats about 20% of all facial and hypoglossal neurons display not only cytoplasmic, but also intranuclear neuron-specific enolase-like immunoreactivity and (2) following any axotomy of the facial or hypoglossal peripheral nerve, the perikarya of all injured motoneurons react by an outstanding increase of neuron-specific enolase-like immunoreactivity in the karyoplasm. Similar findings were obtained in experiments on non-fixed cultured Neuro-2a cells that had been lesioned with hydrogen peroxide. Counting the absolute numbers of normal and reactive neurons at 1-365 days post axotomy revealed that the increase of neuron-specific enolase in neuronal cell nuclei is temporary and reversible. It is first detected at 2 days post axotomy, reaches its maximum at 10-18 days post axotomy and is no longer evident 56 days following surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1986

Histochemical localization of acetylcholinesterase in relation to motor neurons and internuclear neurons of the cat abducens nucleus.

Three distinct patterns of AChE localization have been observed in relation to cat abducens motor neurons and internuclear neurons labelled by retrograde transport of horseradish peroxidase. First, AChE was localized predominantly within cisternae of granular endoplasmic reticulum and agranular reticulum of motor neuron somata, dendrites and axons, but was absent from internuclear neurons. AChE was also associated with saccules of the Golgi apparatus in the motor neurons, but was was absent from all other cytoplasmic organelles. Second, AChE was observed on the soma-dendritic and axonal surface membrane of the motor neurons, particularly at sites of apposition of synaptic endings of all morphological types, but was usually absent from the surface membranes of internuclear neurons. Third, AChE was associated both extracellularly and intracellularly with certain synaptic endings that contained spheroidal synaptic vesicles and that contacted both motor neurons and internuclear neurons. A similar pattern of staining of synaptic endings was observed at the neuromuscular junctions in the lateral rectus muscle. Axotomy of the VIth nerve resulted in loss of intracellular AChE associated with the Golgi apparatus and extracellular AChE on the somatic surface membrane of the motor neurons. The patterned localization of AChE contrasted with the localization of butyrylcholinesterase, which was associated predominantly with astrocytes. The findings suggest different roles of AChE as a function of the different patterns of localization.

Abducens Nerve↗
PubMed1994

Neuronal differentiation in cultures of murine neural crest. II. Development of capsaicin-sensitive neurons.

A subset of neurons differentiating in cultures of mammalian neural crest cells express a sensitivity to the excitotoxin, capsaicin. The properties of the capsaicin-sensitive neurons in the neural crest cultures are similar to those reported for authentic sensory neurons. For example, the application of capsaicin results in a large, rapid depolarization of capsaicin-sensitive neurons. Capsaicin-sensitive neurons were also detected by the influx of cobalt ions. The development of capsaicin sensitivity in neural crest cultures was dependent on time in culture and on the presence of NGF. A major difference between the crest-derived capsaicin-sensitive neurons and authentic sensory neurons was the simultaneous expression of immunoreactivity for ChAT/TH/CGRP by the former neurons. These experiments indicate that a specific physiological property of authentic sensory neurons is expressed by neurons differentiating from the neural crest in vitro.

Action Potentials↗
PubMedDate not supplied

Preliminary evidence: decreased GAP-43 message in tangle-bearing neurons relative to adjacent tangle-free neurons in Alzheimer's disease parahippocampal gyrus.

Loss of synapses has been shown to correlate with the severity of dementia in Alzheimer's disease (AD). Intracellular neurofibrillary tangles (NFTs) have also been shown to correlate to the severity of AD dementia. We have been investigating the influence of NFTs on mRNAs related to neuronal plasticity and synaptic function. We recently reported a decrease in message for the plasticity marker, GAP-43, in AD cases with high tangle densities. The study did not permit us to determine if: a) the decrease in GAP-43 message was specific to the NFT-bearing neurons, b) a general decrease in GAP-43 message was occurring in all surviving neurons, or c) the decrease in GAP-43 message was due to a loss of neurons. It is unlikely a loss of neurons could explain the sixfold GAP-43 message loss we reported, because only a 19% excess decrease in density of hippocampal neurons occurs in AD cases with high tangle densities. Consequently, the study reported here was undertaken to determine if a general decrease in GAP-43 message was occurring in all surviving AD neurons or if the decrease in GAP-43 message was specific to NFT-bearing neurons. We combined immunocytochemistry for neurofibrillary tangles with in situ hybridization for GAP-43 message. We report here preliminary evidence indicating a decrease in GAP-43 message in NFT-bearing neurons compared to adjacent nontangle bearing neurons in parahippocampal cortex of AD patients.

Alzheimer Disease↗
PubMed1989

Identified target motor neuron regulates neurite outgrowth and synapse formation of aplysia sensory neurons in vitro.

To determine the influence that an appropriate target cell has on the axonal structure of a presynaptic neuron in vivo, we examined the morphologies of individual Aplysia sensory neurons in dissociated cell culture in the presence or absence of identified target motor neurons. We find that an appropriate target, the motor cell L7, regulates the morphological differentiation of the presynaptic sensory neurons in two ways: the target induces the axons of the sensory neurons to develop a more elaborate structure and to form active zones, and the target guides the outgrowth of the sensory neurons. The influence of the appropriate target, L7, on the morphological differentiation of sensory neurons appears to be related to the formation of chemical synaptic connections between the sensory neurons and L7, since sensory neurons co-cultured with an inappropriate target motor neuron do not exhibit a comparable elaboration of their axonal processes.

Animals↗
PubMed2004

AML1/Runx1 is important for the development of hindbrain cholinergic branchiovisceral motor neurons and selected cranial sensory neurons.

The mechanisms that regulate the acquisition of distinctive neuronal traits in the developing nervous system are poorly defined. It is shown here that the mammalian runt-related gene Runx1 is expressed in selected populations of postmitotic neurons of the embryonic central and peripheral nervous systems. These include cholinergic branchial and visceral motor neurons in the hindbrain, restricted populations of somatic motor neurons of the median and lateral motor columns in the spinal cord, as well as nociceptive and mechanoreceptor neurons in trigeminal and vestibulocochlear ganglia. In mouse embryos lacking Runx1 activity, hindbrain branchiovisceral motor neuron precursors of the cholinergic lineage are correctly specified but then fail to progress to a more differentiated state and undergo increased cell death, resulting in a neuronal loss in the mantle layer. In contrast, the development of cholinergic somatic motor neurons is unaffected. Runx1 inactivation also leads to a loss of selected sensory neurons in trigeminal and vestibulocochlear ganglia. These findings uncover previously unrecognized roles for Runx1 in the regulation of mammalian neuronal subtype development.

Animals↗
PubMed1993

Serotonin-containing neurons in lobsters: the actions of gamma-aminobutyric acid, octopamine, serotonin, and proctolin on activity of a pair of identified neurons in the first abdominal ganglion.

1. Serotonin has been shown to be an important neurohormone that modulates behavioral output in lobsters. This study explores the neurochemical identity of excitatory and inhibitory inputs to a pair of identified serotonin-containing neurons in the first abdominal ganglion (A1) of the lobster that also contain the pentapeptide proctolin. These neurons are spontaneously active, appear to be driven by an endogenous pacemaking mechanism, and have been shown to play a role in circuits that control behaviorally relevant postures. 2. To explore the exogenous control of neuronal activity, a number of putative neuroactive compounds were superfused over the A1 serotonin-containing neurons in isolated ventral nerve cords. Three amines, gamma-aminobutyric acid (GABA), octopamine, and serotonin, were found to be potent inhibitors in a dose-dependent manner. GABA inhibition had a rapid onset and termination and yielded a transient postinhibitory rebound activity immediately after amine washout; activity eventually returned to the preinhibition level. Octopamine inhibition had a less rapid onset and termination, and the steady-state activity after inhibition was higher than preinhibition firing in most cells (22% of which were statistically significantly increased). Serotonin inhibition had a relatively slow onset and termination, and the steady-state activity after inhibition remained low in most cells (19% significantly decreased). 3. Repeated or prolonged exposure to these three amines reduced the efficacy of inhibition. Three types of desensitization have been empirically defined: 1) rapid desensitization, which tended to dampen the initial inhibition; this was particularly strong for GABA inhibition; 2) low-dose desensitization, in which the A1 serotonin containing neurons became less sensitive to inhibition by a particular concentration of amine after prior exposure to a lower concentration, although the lower concentration may not by itself have had inhibitory effects; this was seen with octopamine inhibition; and 3) long-term desensitization, in which the efficacy of inhibition of a particular amine concentration dwindled with repeated applications (even with up to 160 min washout between applications); this was seen with octopamine and serotonin inhibition, although not for every A1 serotonin-containing neuron analyzed. 4. Bath application of these three amines was still capable of inhibiting the A1 serotonin-containing neurons when inhibitory synaptic transmission was blocked by use of low Ca2+/high Mg2+ solutions. 5. The pentapeptide proctolin excited the A1 serotonin-containing neurons: it activated silent neurons and increased the firing rate of spontaneously active neurons. The excitatory effect outlasted the presence of the peptide.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMed1990

Growth cones of chick sympathetic preganglionic neurons in vitro interact with other neurons in a cell-specific manner.

The ability of the growth cones of sympathetic preganglionic neurons to recognize the neurons they encounter during their outgrowth and to react to them in a cell-type-specific manner may play a role in guiding them to appropriate targets during development in vivo. In this study, we examined the in vitro growth of sympathetic preganglionic neurons as they interacted with motor neurons, dorsal root ganglion neurons, and sympathetic ganglion neurons. All of these cell types might potentially be encountered by a growing preganglionic axon. The interaction of sympathetic preganglionic growth cones with each cell type was distinct. Sympathetic preganglionic growth cones fasciculated on motor-neuron neurites, collapsed after contact with the cell bodies and neurites of dorsal root ganglion neurons, and grew across the cell bodies and neurites of sympathetic ganglion neurons. These cell-type-specific responses stand in contrast to the collapse and retraction reported to be the most common growth-cone behaviors that result from contact between central and peripheral neurons in vitro and suggest that contact-mediated recognition might be sufficient for growth to and interaction with appropriate targets.

Animals↗
PubMed1989

Identified serotonergic neurons LCB1 and RCB1 in the cerebral ganglia of Aplysia produce presynaptic facilitation of siphon sensory neurons.

Several lines of evidence suggest that 5-HT plays a significant role in presynaptic facilitation of the siphon sensory cells contributing to dishabituation and sensitization of the gill- and siphon-withdrawal reflex in Aplysia. Most recently, Glanzman et al. (1989) found that treatment with the 5-HT neurotoxin, 5,7-DHT markedly reduced both synaptic facilitation and behavioral dishabituation. To provide more direct evidence for a role of 5-HT, we have attempted to identify individual serotonergic facilitator neurons. Hawkins (1989) used histological techniques to locate several serotonergic neurons in the ring ganglia that send axons to the abdominal ganglion and are therefore possible serotonergic facilitators. These include one neuron in the B cluster of each cerebral ganglion, which we have identified electrophysiologically and named the CB1 cells. Both glyoxylic acid histofluorescence and 5-HT immunofluorescence indicate that the CB1 neurons are serotonergic. In a semiintact preparation, the CB1 neurons respond to cutaneous stimulation which produces dishabituation and sensitization (such as tail shock) with an increase in firing, which may outlast the stimulation by 15 min. Intracellular stimulation of a CB1 neuron in a manner similar to its response to tail shock produces facilitation of the EPSPs from siphon sensory neurons to motor neurons, as well as broadening of the action potential in the sensory neurons in tetraethylammonium solution. These results strongly suggest that the identified serotonergic CB1 neurons participate in mediating presynaptic facilitation contributing to dishabituation and sensitization of the gill- and siphon-withdrawal reflex in Aplysia.

Animals↗
PubMed1997

Neuron addition during growth of the postmetamorphic bullfrog: sensory neuron and axon number.

Neuron addition is one means whereby the nervous system can compensate for increased body size. Neurons can be added either by mitosis of stem cells or by late differentiation of committed precursors. Previously, the doubling of hind limb dorsal root ganglion (DRG) neurons in postmetamorphic bullfrogs (Rana catesbeiana) was found to occur in the absence of neuron proliferation (St. Wecker and Farel [1994] J. Comp. Neurol. 342:430-438). In the present study, we identify a population of cells in the DRGs of juvenile frogs that lack the appearance typical of sensory neurons yet are immunoreactive to a neuron-specific probe for neurofilament protein. These less differentiated (type-L neurons) could not be labeled retrogradely with horseradish peroxidase from the periphery or dorsal root. Despite their apparent immaturity, type-L neurons appear to have extended axons both centrally and toward the periphery, because axon number in dorsal roots and peripheral nerves was similar in juvenile and adult frogs. These findings are consistent with the existence in juvenile frogs of a population of incompletely differentiated DRG neurons that lack the physiological properties and appearance typical of mature neurons.

Aging↗
PubMed1999

Ability of retinal Müller glial cells to protect neurons against excitotoxicity in vitro depends upon maturation and neuron-glial interactions.

Glutamate is the most abundant excitatory amino acid in the central nervous system. It has also been described as a potent toxin when present in high concentrations because excessive stimulation of its receptors leads to neuronal death. Glial influence on neuronal survival has already been shown in the central nervous system, but the mechanisms underlying glial neuroprotection are only partly known. When cells isolated from newborn rat retina were maintained in culture as enriched neuronal populations, 80% of the cells were destroyed by application of excitotoxic concentrations of glutamate. Massive neuronal death was also observed in newborn retinal cultures containing large numbers of glia, or when neurons were seeded onto feeder layers of purified cells prepared from immature (postnatal 8 day) rat retina. When newborn retinal neurons were seeded onto feeder layers of purified glial cells prepared from adult retinas, application of excitotoxic amino acids no longer led to neuronal death. Furthermore, neuronal death was not observed in mixed neuron/glial cultures prepared from adult retina. However, in all cases (newborn and adult) application of kainate led to amacrine cell-specific death. Activity of glutamine synthetase, a key glial enzyme involved in glutamate detoxification, was assayed in these cultures in the presence or absence of exogenous glutamate. Whereas pure glial cultures alone (from young or adult retina) showed low activity that was not stimulated by glutamate addition, mixed or co-cultured neurons and adult glia exhibited up to threefold higher levels of activity following glutamate treatment. These data indicate that two conditions must be satisfied to observe glial neuroprotection: maturation of glutamine synthetase expression, and neuron-glial signalling through glutamate-elicited responses.

Animals↗
PubMed2002

Corticotropin-releasing hormone-synthesizing neurons of the human hypothalamus receive neuropeptide Y-immunoreactive innervation from neurons residing primarily outside the infundibular nucleus.

Immunohistochemical single- and double-labeling studies were performed on the hypothalami of postmortem human brains to elucidate the distribution of corticotropin-releasing hormone (CRH)-immunoreactive (IR) neuronal elements and their interaction with the neuropeptide Y (NPY)-ergic neuronal system. The great majority of CRH-IR perikarya were found in the paraventricular nucleus (PVN), whereas a considerable number of CRH-IR neurons were also observed in the periventricular and infundibular nuclei. The dorsomedial nucleus and the perifornical region contained only scattered CRH-IR neurons. Dense CRH-IR fiber networks were found throughout the hypothalamus. However, the medial preoptic, the dorsolateral part of the supraoptic, the suprachiasmatic, the ventromedial, and the different mammillary nuclei showed a relative paucity of fibers. The terminal fields of NPY-IR axons overlapped the distribution of CRH-IR neurons in the hypothalamus. NPY-IR axon varicosities were juxtaposed to both dendrites and perikarya of the majority of CRH-IR neurons residing in the paraventricular, periventricular, and infundibular nuclei. These neurons were frequently contacted by multiple NPY axons that either formed baskets around their perikarya or completely ensheathed the emanating CRH dendrites. Because NPY and agouti-related protein (AGRP) are co-contained in neurons of the human infundibular nucleus, we used AGRP as a marker of NPY fibers originating exclusively from the infundibular nucleus. Only a small proportion of CRH neurons in the PVN was contacted by AGRP-IR axon varicosities, suggesting that NPY-IR innervation of CRH neurons in the PVN derive mainly from regions outside the infundibular nucleus. The present morphological findings support the view that NPY regulates the CRH system of the human hypothalamus and therefore at least some of the effects of NPY on metabolic, autonomic, and endocrine functions may be mediated through CRH.

Adult↗