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At least 847 records · Page 47Linked to original sources
PubMed2002

Orexin/hypocretin neurons: chemical phenotype and possible interactions with melanin-concentrating hormone neurons.

We showed earlier that a specific neuron population of the rat lateral hypothalamus, differing from the codistributed melanin-concentrating hormone (MCH) neurons, express both dynorphin (DYN) and secretogranin II (SgII) genes. We demonstrated later that this population corresponds in fact to the newly identified orexin/hypocretin (OX/Hcrt) neurons. In the present study, by revisiting the chemical phenotype of these neurons, we confirm that all of them contain DYN B- and SgII-immunoreactive materials. The roles played by these peptide/protein in OX/Hcrt neurons are still unclear. Double immunocytochemical stainings highlight putative somasomatic, axosomatic and axodendritic contacts between OX/Hcrt and MCH neurons. Adding OX/Hcrt to the culture medium of hypothalamic slices from 8-day-old rats results either in a significant increase of MCH mRNA after 24 h survival or a strong fall after 10 days culture. These results taken together suggest that OX/Hcrt can directly and/or indirectly affect MCH expression, and that both OX/Hcrt and MCH neuron populations interact to respond in a coordinated manner to central and peripheral signals.

Animals↗
PubMed1999

Calcium phosphate-mediated transfection of primary cultured brain neurons using GFP expression as a marker: application for single neuron electrophysiology.

We investigated the efficiency of transfecting primary cultured rat postnatal brain neurons (substantia nigra pars compacta neurons and locus coeruleus neurons) with cDNA encoding GFP (jellyfish green fluorescent protein) using a calcium phosphate method. The proportion of transfected neurons (transfection efficiency) was approximately 5%, when cultures from the substantia nigra pars compacta were transfected 3 days after plating. The transfection efficiency decreased when cultures were transfected 10 days after plating (1.7%). Neurons were cotransfected at a very high probability ( > 78%) with the muscarinic m2-receptor cDNAs together with GFP plasmids. Transfected neurons were very healthy as indicated by the zero-current potential and the microscopical appearance. Because the transfection efficiency is low, this method cannot be used for experiments involving the whole cell population. The transfection efficiency of 1.7% corresponded to approximately 20 transfected cells per dish in our culture conditions and these cells are sufficient in number for electrophysiological studies. Therefore, this is an excellent method for studying the influence of exogenous genes on single neurons using electrophysiological techniques.

Animals↗
PubMed1999

Absence of binding activity of neuron-restrictive silencer factor is necessary, but not sufficient for transcription of NMDA receptor subunit type 1 in neuronal cells.

Neuron-restrictive silencer factor (NRSF, also termed REST) has been proposed to restrict expression of a set of genes to neurons by blocking their transcription in nonneuronal cells. The N-methyl-D-aspartate (NMDA) receptor subunit type I (NR1) gene contains a consensus sequence for the NRSF/REST binding site (NRSE/RE1). In this study, we evaluated the contribution of NRSF/REST to neuronal specificity of the NR1 gene. NR1 mRNA expression correlates with the absence of NRSF/REST binding activity, rather than expression of NRSF/REST protein, in several cell lines, suggesting that the absence of NRSF/REST-binding activity is necessary for the expression of the NR1 gene. HeLa cells, which do not express the NR1 gene, have NRSF/REST binding activity to the NR1 NRSE/RE1, resulting in inhibition of NR1 promoter activity. However, we also found that two nonneuronal cell lines (C6 glioma and P19 embryonal carcinoma) that lack NRSF/REST-binding activity, manifest only small amounts of NR1 mRNA compared to neuronal cell lines (PC12 pheochromocytoma and neuronally differentiated P19 cells). The enhancement of NR1 mRNA levels during neuronal differentiation of P19 cells is accompanied by an increase in NR1 promoter activity in an NRSF/REST-binding independent manner. Our results suggest therefore that the absence of NRSF/REST-binding activity is necessary but not sufficient for robust NR1 transcription in neuronal cells.

Animals↗
PubMed2002

Cyclic guanosine 5' monophosphate (GMP) prevents expression of neuronal nitric oxide synthase and apoptosis in motor neurons deprived of trophic factors in rats.

Deprivation of trophic factors induces expression of neuronal nitric oxide synthase (NOS) and nitric oxide production in cultured motor neurons, leading to apoptosis. Motor neuron apoptosis requires the simultaneous production of nitric oxide and superoxide and is associated with increased nitrotyrosine immunoreactivity. Nitric oxide also stimulates cyclic guanosine 5' monophosphate (cGMP) synthesis, which enhances the survival of motor neurons treated with brain derived trophic factor (BDNF). Here we report that cGMP analogs blocked neuronal NOS induction, nitrotyrosine accumulation, and prevented apoptosis for up to 3 day of motor neurons deprived of trophic factors. Low concentrations of exogenous nitric oxide (<100 nM), which are not toxic for BDNF-treated cultures, reversed the protective effect of cGMP. These results suggest that elevation of cGMP could decrease nitric oxide production, and thereby preventing motor neuron apoptosis.

Animals↗
PubMed2001

Colocalization of GluR1 and neuronal nitric oxide synthase in rat nucleus tractus solitarii neurons.

Previously we demonstrated that glutamate and neuronal nitric oxide synthase (nNOS) containing neuronal elements are frequently apposed in subnuclei of the rat nucleus tractus solitarii. It is known that glutamate receptors (GluRs) of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subtype participate in cardiovascular regulation by the nucleus tractus solitarii and that responses to AMPA receptor activation may be linked to NO. Therefore, in the present study, we further tested the hypothesis that the calcium-permeable subunit GluR1 of AMPA type GluRs and nNOS are colocalized in neurons of the nucleus tractus solitarii. Distribution of GluR1 and nNOS in rat nucleus tractus solitarii was investigated by double fluorescent immunohistochemistry combined with confocal laser scanning microscopy. Numerous GluR1 immunoreactive cells and fibers were present in subnuclei of the nucleus tractus solitarii. The staining intensity of GluR1 immunoreactive cells varied among subnuclei. Cells in the interstitial subnucleus contained the highest GluR1 staining intensity. A moderate intensity of staining was present in the intermediate, dorsolateral, ventral, and commissural subnuclei. A slightly lower level of GluR1 immunoreactivity was present in cells of the medial subnucleus. Cells in the central subnucleus contained a low level of GluR1 immunoreactivity. The staining intensity of GluR1 immunoreactive fibers also varied among subnuclei. Distribution of nNOS immunoreactivity in the nucleus tractus solitarii and other brain stem areas was the same as in our earlier reports. Superimposition of confocal images of nNOS immunoreactivity and GluR1 immunoreactivity allowed us to identify double-labeled structures. Nearly all neurons that were immunoreactive for nNOS contained GluR1 immunoreactivity, but only a proportion of GluR1 immunoreactive cells contained nNOS immunoreactivity. Double-labeled neurons were present in all subnuclei of the nucleus tractus solitarii. The percentages of GluR1 immunoreactive cells that also contained nNOS immunoreactivity differed among subnuclei of the nucleus tractus solitarii. Fibers that labeled for nNOS alone, GluR1 alone or both were present among labeled cells in these subnuclei. These data support the hypothesis that GluR1 and nNOS are colocalized in neurons of nucleus tractus solitarii. The demonstration of this anatomical relationship provides further anatomical support for the hypothesis that activation of AMPA receptors on neurons that synthesize NO in the nucleus tractus solitarii contributes to autonomic regulation.

Animals↗
PubMed2002

Reversal of neuronal polarity characterized by conversion of dendrites into axons in neonatal rat cortical neurons in vitro.

The mechanisms for the establishment and maintenance of cell polarity in neurons are not well understood. Axon regeneration from dendrites has been reported after axotomy near the cell body in vivo. We report here in vitro a reversal of neuronal polarity characterized by the conversion of dendrites into axons. We isolated neurons from the neonatal rat cerebral cortex. Neurons that exhibited an apical dendrite with a length of >100 microm were monitored for 3 days in culture. In 66% of neurons examined, a new axon, as identified by reactivity with an antibody to dephosphorylated tau or by lack of reactivity with an antibody to the a and b isoforms of microtubule-associated protein 2, appeared to form from the tip of the original dendrite. Further analysis of such neurons revealed that the distal half of the original dendrite became positive for dephosphorylated tau or negative for microtubule-associated protein 2. Time-lapse video microscopy demonstrated the conversion of the original dendrite into an axon without dendritic retraction. Axon regeneration from dendritic tips required a significantly longer time than axon regeneration from minor processes. Our observations thus demonstrate in vitro a time-consuming reversal of neuronal polarity and the conversion of a dendritic cytoskeleton into an axonal one.

Actins↗
PubMed1997

Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death.

Recently, erythropoietin has been shown to be produced by astrocytes and its production is hypoxia-inducible. In the present study, we demonstrated, using a reverse transcription-polymerase chain reaction assay and immunostaining of the cells, that the erythropoietin receptor was expressed in cultured hippocampal and cerebral cortical neurons of day 19 rat embryo. Erythropoietin protected the cultured neurons from glutamate neurotoxicity. Neurons cultured for seven to 10 days were exposed to glutamate for 15 min and after culture for a further 24 h in the absence of glutamate the neuron survival was assayed. Significant protection was observed with erythropoietin from 3 pM (c. 100 pg/ml) in a dose-dependent manner. The protection was completely reversed by co-application of a soluble erythropoietin receptor, an extracellular domain capable of binding with erythropoietin. For exhibition of the neuroprotective effect, exposure of neurons to erythropoietin approximately 8 h prior to exposure to glutamate was required. Experiments with the inhibitors indicated that RNA and protein syntheses were necessary for the protection. However, exposure to erythropoietin for a short period (5 min or less) was sufficient to elicit the protective effect. The protective effect of erythropoietin was blocked by the simultaneous addition of EGTA. These findings and the previous finding that erythropoietin induces a rapid and transient increase in intracellular Ca2+ concentration in neuronal cells suggest that erythropoietin plays a neuroprotective role in brain injury caused by hypoxia or ischemia and that erythropoietin-induced Ca2+ influx from outside of the cells is a critical initial event yielding an enhanced resistance of the neurons to glutamate toxicity.

Animals↗
PubMed1998

Dissociation of dorsal root ganglion neurons into afferent and efferent-like neurons.

Although the textbook function of dorsal root ganglion neurons is to signal information to the brain, a group of C-fibre and some A delta-fibre afferents have the capacity to release peptide transmitters from their peripheral terminations and thereby to regulate vascular and other tissue activities. Depending on the species under study, vasoactive dorsal root ganglion neurons in the skin belong to heat nociceptors or a subclass of polymodal nociceptors, and it has been a matter of long-standing discussion how the local effector role of dorsal root ganglion neurons is related to their afferent function. The observation that local vascular regulation may take place independently of nociception has commonly been explained by a number of transductional differences between peripheral peptide release and afferent nerve activity. However, the view that it is only one population of dorsal root ganglion neurons that can work in either mode is increasingly challenged, and after consideration of the available information we hypothesize that some dorsal root ganglion neurons are specialized in controlling peripheral effector mechanisms but have no role in sensation. These local effector neurons represent a novel class of autonomic neurons that lack a preganglionic input, but operate in an efferent-like mode after stimulation by internal or external stimuli.

Afferent Pathways↗
PubMed2004

The focality of the global Alzheimer brain process: is the selective vulnerability of neurons a specific phenomenon of primary neuronal pathobiology?

A focality in the development of a global series of predisposing factors that conditions a progressiveness in the neurodegenerative process of Alzheimer type would appear to arise as a specific lesion of the neuron. Such a neuronal lesion would perhaps disrupt functional connectivity of neuronal networks in a process involving loss of neuronal viability. Indeed, a strict concept of selective vulnerability of neurons in the Alzheimer brain might be simply a preconditioning by microenvironmental factors that interacts with the individual neuron in terms of cellular component depletion or in terms of plasmalemmal disruption. In a final analysis, perhaps, the individual neuron would appear as the essential focus of a process that would account for a conditioning globality of the Alzheimer process that promotes both progressiveness and irreversibility of the brain pathology.

Alzheimer Disease↗
PubMed2001

Isolation of neuronal precursors from differentiating P19 embryonal carcinoma cells by neuronal T alpha 1-promoter-driven GFP.

The induction of pluripotent P19 embryonal carcinoma (EC) cells with retinoic acid results in their differentiation into cells that resemble neurons, glia, and fibroblasts. To isolate and enrich the developing neurons from heterogeneously differentiating P19 EC cells, we used a recently introduced protocol combining the expression of green fluorescent protein (GFP) driven by a tissue-specific promoter and fluorescence-activated cell sorting. Cells were transfected with the gene for GFP, which is under the control of the neuronal T alpha 1 tubulin promoter. After four days of retinoic acid treatment, GFP was specifically detected in cells undergoing neuronal differentiation. Sorting of fluorescent differentiating P19 EC transfectants yielded populations highly enriched in neuronal precursors and neurons. Immunoreactivity for nestin and neurofilament was observed in 80 and 25% of the sorted cell population, respectively. These results demonstrate that differentiated neuronal precursor cells can be efficiently isolated from differentiating pluripotent embryonic cells in vitro, suggesting that this method can reproducibly provide homogeneous materials for further studies on neurogenesis.

Antineoplastic Agents↗
PubMed2000

Targeted neuronal death affects neuronal replacement and vocal behavior in adult songbirds.

In the high vocal center (HVC) of adult songbirds, increases in spontaneous neuronal replacement correlate with song changes and with cell death. We experimentally induced death of specific HVC neuron types in adult male zebra finches using targeted photolysis. Induced death of a projection neuron type that normally turns over resulted in compensatory replacement of the same type. Induced death of the normally nonreplaced type did not stimulate their replacement. In juveniles, death of the latter type increased recruitment of the replaceable kind. We infer that neuronal death regulates the recruitment of replaceable neurons. Song deteriorated in some birds only after elimination of replaceable neurons. Behavioral deficits were transient and followed by variable degrees of recovery. This raises the possibility that induced neuronal replacement can restore a learned behavior.

Age Factors↗
PubMed2002

Xiro homeoproteins coordinate cell cycle exit and primary neuron formation by upregulating neuronal-fate repressors and downregulating the cell-cycle inhibitor XGadd45-gamma.

The iroquois (iro) homeobox genes participate in many developmental processes both in vertebrates and invertebrates, among them are neural plate formation and neural patterning. In this work, we study in detail Xenopus Iro (Xiro) function in primary neurogenesis. We show that misexpression of Xiro genes promotes the activation of the proneural gene Xngnr1 but suppresses neuronal differentiation. This is probably due to upregulation of at least two neuronal-fate repressors: XHairy2A and XZic2. Accordingly, primary neurons arise at the border of the Xiro expression domains. In addition, we identify XGadd45-gamma as a new gene repressed by Xiro. XGadd45-gamma encodes a cell-cycle inhibitor and is expressed in territories where cells will exit mitosis, such as those where primary neurons arise. Indeed, XGadd45-gamma misexpression causes cell cycle arrest. We conclude that, during Xenopus primary neuron formation, in Xiro expressing territories neuronal differentiation is impaired, while in adjacent cells, XGadd45-gamma may help cells stop dividing and differentiate as neurons.

Amino Acid Sequence↗
PubMed1994

Characterization of identifiable neurones in the head ganglia of the parasitic nematode Ascaris suum: a comparison with central neurones of Caenorhabditis elegans.

Intracellular recordings have been made from neurones in the head ganglia of Ascaris. The neurones had low resting membrane potentials of -21 +/- 9 mV (n = 78) and a relatively high input resistance (e.g. 25 M omega for a 100 microns cell). In all cases the intracellular location of the recording electrode was verified by injection of the fluorescent marker, 5,6-carboxyfluorescein (CBXF). To ascertain whether or not the low membrane potential was due to impalement damage, the same neurone was recorded from using two microelectrodes. The membrane potential following the first impalement by a 20 M omega 3 M KCl electrode was -38 mV and following the second impalement by a 80 M omega CBXF (for subsequent intracellular labelling) electrode was decreased to -34 mV. Input resistance of these cells was estimated using both single and two electrode intracellular recording techniques and in both cases yielded a relatively high value for the size of cell (e.g. 25 M omega for a 100 microns cell). Neurones labelled by intracellular injection of the fluorescent marker 5,6-carboxyfluorescein were morphologically simple and lacked extensive arborizations. The dorsal ganglion is a discrete structure consisting of only 3 neurones. Here we compare the morphological properties of these neurones to those described in the dorsal ganglion of Caenorhabditis elegans. The whole mount preparation of Ascaris ganglia thus provides a useful model to study the functional properties of neurones in nematode central nervous system and presents the possibility to assess central sites of action for anthelmintics.

Animals↗
PubMed1999

Expression and regulation of NMDA receptor subunit R1 and neuronal nitric oxide synthase in cortical neuronal cultures: correlation with cytochrome oxidase.

Our previous studies showed a differential distribution of the glutamatergic terminals in cytochrome oxidase-rich and -poor regions of the visual cortex. The NMDA type of glutamate receptors have been proposed to be involved in the activation of nitric oxide synthase to produce nitric oxide, the neurotransmitter. In the present study, we hypothesized that the expressions of glutamate receptor, NMDA receptors (NMDAR1) and neuronal nitric oxide synthase (nNOS) were colocalized and were also correlated with that of cytochrome oxidase (CO) in a subset of neurons. We used primary cultures of postnatal rat visual cortical neurons as a model system, so that we could examine both the somatic and dendritic expressions of these neurochemicals in individual neurons. We found a difference in the sequence of developmental expressions of NMDAR1, nNOS, CO, and Na(+)/K(+) ATPase. Triple labeling showed that all nNOS-positive neurons were immunoreactive for NMDAR1, and a subpopulation of them had high CO activity. The expression of NMDAR1 was positively correlated with CO activity. This is consistent with our previous finding that CO activity is strongly governed by excitatory glutamatergic synapses. After 40 hours of depolarizing potassium chloride treatment, CO activity was increased, and NMDAR1and nNOS levels were up-regulated in parallel. One week of tetrodotoxin significantly decreased the expression of NMDAR1, nNOS, and CO activity. Our results demonstrate that NMDA receptors and nNOS do co-exist in a subset of neurons that have high CO activity and their expressions are under the control of neuronal activity.

Animals↗
PubMed2001

Effects of GABA(A) receptor partial agonists in primary cultures of cerebellar granule neurons and cerebral cortical neurons reflect different receptor subunit compositions.

Based on an unexpected high maximum response to piperidine-4-sulphonic acid (P4S) at human alpha1alpha6beta2gamma2 GABA(A) receptors expressed in Xenopus oocytes attempts to correlate this finding with the pharmacological profile of P4S and other GABA(A) receptor ligands in neuronal cultures from rat cerebellar granule cells and rat cerebral cortex were carried out. GABA and isoguvacine acted as full and piperidine-4-sulphonic acid (P4S) as partial agonists, respectively, at alpha1beta2gamma2, alpha6beta2gamma2 and alpha1alpha6beta2gamma2 GABA receptors expressed in Xenopus oocytes with differences in potency. Whole-cell patch-clamp recordings were used to investigate the pharmacological profile of the partial GABA(A) receptor agonists 4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridin-3-ol (THIP), P4S, 5-(4-piperidyl)isoxazol-3-ol (4-PIOL), and 3-(4-piperidyl)isoxazol-5-ol (iso-4-PIOL), and the competitive GABA(A) receptor antagonists Bicuculline Methbromide (BMB) and 2-(3-carboxypropyl)-3-amino-6-methoxyphenyl-pyridazinium bromide (SR95531) on cerebral cortical and cerebellar granule neurons. In agreement with findings in oocytes, GABA, isoguvacine and P4S showed similar pharmacological profiles in cultured cortical and cerebellar neurones, which are known to express mainly alpha1, alpha2, alpha3, and alpha5 containing receptors and alpha1, alpha6 and alpha1alpha6 containing receptors, respectively. 4-PIOL and iso-4-PIOL, which at GABA(A) receptors expressed in oocytes were weak antagonists, showed cell type dependent potency as inhibitors of GABA mediated responses. Thus, 4-PIOL was slightly more potent at cortical neurones than at granule neurones and iso-4-PIOL was more potent in inhibiting isoguvacine-evoked currents at cortical than at granule neurons. Furthermore the maximum response to 4-PIOL corresponded to that of a partial agonist, whereas that of iso-4-PIOL gave a maximum response close to zero. It is concluded that the pharmacological profile of partial agonists is highly dependent on the receptor composition, and that small structural changes of a ligand can alter the selectivity towards different subunit compositions. Moreover, this study shows that pharmacological actions determined in oocytes are generally in agreement with data obtained from cultured neurons.

Animals↗
PubMed1997

Neuronal synchronization and ionic mechanisms for propagation of excitation in the functional network of immortalized GT1-7 neurons: optical imaging with a voltage-sensitive dye.

Immortalized gonadotropin releasing hormone (GnRH) neurons (GT1 cell line) in culture release GnRH in a pulsatile manner, suggesting that GT1 cells form a functional neuronal network. Optical imaging techniques and a voltage-sensitive fluorescent dye (RH795) were used to study the mechanism of neuronal synchronization and intercellular communication in cultured GT1-7 cells (one of the subclones of the GT1 cell line). The majority (79%) of GT1-7 cells in contact with one another revealed synchronized fluctuations in spontaneous neuronal activity. When a cell in contact with other cells was electrically stimulated, the evoked excitation was propagated to neighbouring cells. The ionic mechanisms involved in the propagation of electrical signals between interconnected GT1-7 cells were investigated using various blockers of Na+, Ca2+ and K+ channels. The propagation of stimulus-evoked excitation was prevented by the voltage-dependent Na+ channel blocker tetrodotoxin. It was also prevented by the voltage-dependent Ca2+ channel blockers, Ni+ (nonselective), nimodipine (L-type) and flunarizine (T-type > L-type), but not apparently affected by omega-agatoxin IVA (P- and Q-type) and omega-conotoxin MVIIA (N-type). The propagation was not influenced by the K+ channel blockers, quinine, tetraethylammonium and Ba2+, but in some cases, it was enhanced by 4-aminopyridine (4-AP) and prevented by apamin. These results suggest that voltage-dependent Na+ channels and L- and T-type Ca2+ channels are involved in the propagation of electrical signals in the GT1-7 neuronal network. Ionic mechanisms, through 4-AP- or apamin-sensitive K+ channels, also seem to be involved in the regulation of signal propagation. These mechanisms may underlie the functioning of the neuronal network formed by immortalized GnRH neurons.

Animals↗
PubMed2000

Pindolol excites dopaminergic and adrenergic neurons, and inhibits serotonergic neurons, by activation of 5-HT1A receptors.

Pindolol accelerates the clinical actions of selective serotonin reuptake inhibitors (SSRIs) in man, and modulates extracellular levels of monoamines in corticolimbic structures in rats. Herein, we examined its influence upon electrical activity of serotonergic, dopaminergic and adrenergic perikarya in the dorsal raphe nucleus (DRN), ventral tegmental area (VTA) and locus coeruleus (LC) of anaesthetized rats. In analogy to the serotonin1A (5-HT1A) agonist, 8-OH-DPAT (-100%), pindolol dose-dependently (0.063- 1.0 mg/kg) decreased (-70%) the firing rate of serotonergic neurons. The inhibitory action of pindolol was abolished by the selective 5-HT1A antagonist, WAY-100,635 (0.031 mg/kg). In contrast, 8-OH-DPAT (+26%) and pindolol (0.25-4.0 mg/kg, +60%) dose-dependently increased the firing rate of dopaminergic cells. Of 57 neurons recorded (pindolol, 2.0 mg/kg), 36 (63%) were excited, 11 (19%) were unaffected and 10 (18%) were inhibited. This variable influence could be attributed to regularly firing neurons in the parabrachial subdivision, inasmuch as all neurons in the paranigral subnucleus were excited. The facilitation of firing by pindolol was accompanied by an increase in burst firing throughout the VTA. Both the increases in burst firing and in firing rate were reversed by WAY-100,635 (0.031 mg/kg). Finally, the electrical activity of adrenergic neurons was dose-dependently enhanced by 8-OH-DPAT and pindolol (+99% and +83%, respectively). WAY-100,635 reversed this excitation and, itself, inhibited the activity of adrenergic neurons. In conclusion, via engagement of 5-HT1A receptors, pindolol inhibits serotonergic, and activates dopaminergic and adrenergic, neurons in anaesthetized rats. Such actions may contribute to its influence upon mood, both alone and in association with antidepressant agents.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2002

CNS neurons express two distinct plasma membrane electron transport systems implicated in neuronal viability.

Trans-plasma membrane electron transport is critical for maintaining cellular redox balance and viability, yet few, if any, investigations have studied it in intact primary neurons. In this investigation, extracellular reduction of 2,6-dichloroindophenol (DCIP) and ferricyanide (FeCN) were measured as indicators of trans-plasma membrane electron transport by chick forebrain neurons. Neurons readily reduced DCIP, but not FeCN unless CoQ(1), an exogenous ubiquinone analog, was added to the assays. CoQ(1) stimulated FeCN reduction in a dose-dependent manner but had no effect on DCIP reduction. Reduction of both substrates was totally inhibited by epsilon-maleimidocaproic acid (MCA), a membrane-impermeant thiol reagent, and slightly inhibited by superoxide dismutase. Diphenylene iodonium, a flavoenzyme inhibitor, completely inhibited FeCN reduction but had no affect on DCIP reduction, suggesting that these substrates are reduced by distinct redox pathways. The relationship between plasma membrane electron transport and neuronal viability was tested using the inhibitors MCA and capsaicin. MCA caused a dose-dependent decline in neuronal viability that closely paralleled its inhibition of both reductase activities. Similarly capsaicin, a NADH oxidase inhibitor, induced a rapid decline in neuronal viability. These results suggest that trans-plasma membrane electron transport helps maintain a stable redox environment required for neuronal viability.

2,6-Dichloroindophenol↗