摘要:

AbstractChanges in neurotransmitter systems of the spinal cord were studied in response to peripheral nerve injury. The uptake and compartmentalization of radiolabeled spinal cord neurotransmitters and transmitter precursors were examined as a function of time following unilateral sciatic nerve crush in adult mice. Accumulation of transmitter was measured within synaptosomally enriched fractions prepared using combinations of differential and density gradient centrifugations. The amount of transmitter substance recovered from these fractions was strongly depedent upon the amount of time following nerve injury and on the specific transmitter or precursor being examined (GABA, glutamate, glycine, and choline chloride). However, for each of these substances, uptake values returned to control levels within nine to twelve days after nerve crush. Localization of GABA changes postcrush revealed reciprocal differences between ipsilateral and contralateral sides of the spinal cord, as well as differences between segmental levels. Altered GABA uptake may reflect changes in the postcrush microchemical environment present during tissue processing, but may also be related to direct changes in the synaptic binding, transport, and compartmentalization of transmitter substance. The time course, magnitude, and direction of these neurochemical changes follow those observed neurophysiologically, and may thus underlie injury‐induced short‐term (days) alterations reported in primary afferent depolarizations, cross cord responses, and other spinal mechani

ISSN:0887-4476    

DOI:10.1002/syn.890020202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe rat cerebellum was previously shown to contain two polypeptides, a hexadecapeptide termed cerebellin and an apparent metabolite des‐Ser1‐cerebellin. The cerebellins have a high degree of sequence homology with residues 625–641 of the polyimmunoglobulin (polyIg)‐receptor adjacent to its membrane‐spanning domain. Since the cerebellins are localized in Purkinje cells and enriched in synaptosomes, this might indicate that cerebellin is a specific proteolytic cleavage fragment of a synaptic protein involved in the transcytosis of an unknown ligand. Using a specific cerebellin radioimmunoassay described here combined with high‐performance liquid chromatography, cerebellin immunoreactivity could be demonstrated in the cerebella of all vertebrates examined from man to chicken. Cerebellin immunoreactivity is localized to Purkinje cells in the rat, mouse, and chicken. Furthermore, cerebellin expression is under developmental regulation in both the chicken and mouse. In addition, neurodevelopmental mutations of mice that eliminate granule cells cause a large deficit in cerebellin levels, suggesting some form of transneuronal

ISSN:0887-4476    

DOI:10.1002/syn.890020203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractCerebellin is a hexadecapeptide that has been biochemically characterized and localized to cerebellar Purkinje cells and certain neurons of the dorsal cochlear nucleus (DCoN) of rat. Among rabbit antisera produced to synthetic cerebellins, one (C1) gave specific immunostaining of the Purkinje neuronal cell body, initial axon segment, and main stem dendrites, while another (R2) reacted with peripheral dendritic structures. This complementarity of staining was also present during cerebellar development. By electron microscopy, the immunoreaction product was localized to polyribosomal domains with antiserum C1and to dendritic spines with antiserum R2, in both cerebellar cortex and DCoN. In the spine, the structure most strongly stained was the postsynaptic density, but some reaction product was adsorbed to the plasma membrane, the spine apparatus, and the granulofibrillar cytoplasmic component. Antiserum R2also stained lysosome‐like bodies. We suggest that antiserum C1recognizes cerebellin precursor(s) and antiserum R2mature peptide(s) and perhaps degradation product. There is structural homology between cerebellin and residues 625–641 of the polyimmunoglobulin transporter. The functional implications of this homology and other possible roles of cerebellin are discus

ISSN:0887-4476    

DOI:10.1002/syn.890020204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe natural alkaloid (‐)PHY is a reversible anticholinesterase carbamate, but in contrast, its optical isomer (+)PHY, is a very weak anticholinesterase. We have shown that treatment of rats with atropine and (‐)PHY prior to injections of a lethal dose of the irreversible organophosphate sarin (0.13 mg/kg) not only protected 100% of the animals from lethality but also reduced the size of the subneural lesions of the nicotinic synapses of skeletal muscle. Similar protection against lethality is provided by pretreatment with (+)PHY. At the concentration used (0.3 mg/kg), there was no detectable inhibition of AChE activity. We have examined the protection afforded by (+)PHY or (‐)PHY against lethality and myopathy due to organophosphate agents such as sarin. The major alterations in the soleus motor endplates 1 hr after drug treatment were as follows: (1) A single sublethal dose of sarin (0.08 mg/kg) produced enlarged, blistered, and severely disrupted subjunctional regions, with muscle damage extendig beyond the endplate to include myofiber necrosis and subsequent phagocytosis; (2) (+)PHY (0.3 mg/kg) produced no obvious damage in the postjunctional region; (3) (‐)PHY (0.1 mg/kg) had a selective effect in inducing irregularities of the subjunctional sarcomere band patterns without any gross vacuolization; (4) light microscopic data indicated that the combination of atropine and (+)PHY, or of atropine and (‐)PHY (0.1 mg/kg), 30 min prior to a lethal dose of sarin, offered dramatic reduction in the average dimension of lesions. Lesions were detectable in most endplates but recognizable changes were markedly less severe than those seen in sarin myopathy. Few instances of extensive muscle damage and myofiber necrosis were visible.In each of the 3 experimental groups examined, the extrajunctional myopathy was reversible with substantial recovery being observed on days 5 and 10 after drug treatment.In addition to its anticholinesterase activity, (‐)PHY is also a powerful ion channel blocker of the nicotinic acetylcholine receptor. As for (+)PHY, its protective effect almost certainly does not depend at inhibition of acetylcholinesterase, but as with (‐)PHY, it my depend on a direct blockade at the nicotinic‐acetylcholine receptor and

ISSN:0887-4476    

DOI:10.1002/syn.890020205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractA total of 769 neuromuscular junction profiles (on 221 muscle fibers) from 21 normal (C57BL/6J +/+), 6 heterozygous (C57BL/6J dy2J/+) and 22 homozygous dystrophic (C57BL/6J dy2J/dy2J) gastrocnemius were photographed in electron microscopy. The fast and slow twitch muscle fibers were differentiated by the width of the Z lines. The number of secondary postjunctional folds per unit length of synaptic cleft was lower in dystrophic than in normal animals. Intermediate values were obtained in heterozygous animals. The length of the postsynaptic membrane was measured and normalized by dividing it by the length of the cross‐section through the synaptic cleft. This normalized length of postjunctional membrane was significantly reduced by 45% in dystrophic animals relative to normals animals and by 41% relative to heterozygous animals. The depth of the secondary folds was also significantly reduced in dystrophic animals relative to normal animals in both fast and slow twitch fibers. These morphometric changes of the postjunctional membrane were observed on NMJs whose nerve terminals were not significantly modified by the dystrophic process and were sometimes observed on apparently normal muscle fiber

ISSN:0887-4476    

DOI:10.1002/syn.890020206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe subcellular localization and the secretion of neuropeptide Y were studied in sympathetic nerve endings of bovine vas deferens.Immunostaining revealed a parallel distribution for neuropeptide Y and dopamine‐β‐hydroxylase immunoreactivity in the network of varicose nerve fibers in the smooth muscle layers of the vas deferens.Following differential centrifugation and sucrose density gradient centrifugation, neuropeptide Y was found to coincide with noradrenaline in the more dense region of the gradient, where the large dense cored vesicles are found.Superfusion experiments demonstrated the release of neuropeptide Y and noradrenaline upon electrical stimulation. Furthermore, the neuropeptide Y secretion was shown to be Ca2+‐dependent.We conclude that in the bovine vas deferens neuropeptide Y is only present in large dense cored vesicles of adrenergic neurons and that the peptide and noradrenaline are coreleased from these vesicles in a calcium dependent

ISSN:0887-4476    

DOI:10.1002/syn.890020207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractRecent reports have demonstrated that the synthetic gamma‐aminobutyric acid (GABA)‐derivative, SR 95531 [2‐(3′‐carbethoxy‐2′‐propyl)‐3‐amino‐6‐paramethoxy‐phenyl‐pyridazini‐um bromide], possesses selective GABAAsites, this agent has been used to identify GABAAreceptors. In the present investigation, we studied the binding of [3H]SR 95531 to tissue sections of rat brain using microscopic analysis of receptor localization. The appropriate binding conditions for defining GABAAreceptors with this radioligand were obtained by determining the dissociation and association kinetics, and performing saturation and displacement studies. Using membrane preparations from whole rat brain (or brain regions representing cortex, striatum, hippocampus, midbrainthalamus, medulla‐pons and cerebellum), saturation and displacement studies were analyzed, and allosteric modulation of [3H]SR 95531 binding was examined by including several benzodiazepine and barbiturate receptor ligands in the incubation media. To assess the stereoselective properties of [3H]SR 95531 binding in rat membranes, numerous barbiturates were added during the incubation. The binding of [3H]SR 95531 was demonstrated to be saturable, specific and to bind with relatively high affinity to low‐affinity GABAAsites. Scatchard analysis performed on saturation data of binding to tissue sections showed a dissociation constant (KD) of 42.4 nM and a maximum number of binding sites (Bmax) of 105.8 fmol/mg tissue. Microscopic analysis showed that intermediate to high densities of [3H]SR 95531 binding occurred in brain regions containing intermediate to high densities of low‐affinity GABAAsites. Results from competition studies demonstrated that [3H]SR 95531 is displaceable by GABAAagents and displaced preferentially by GABAAantagonists. Scatchard analysis of saturation experiments from membrane preparations indicated that the KDand Bmaxfrom the centrifugation assay was 53.0 nM and 4.26 pmol/mg protein, respectively. Using the filtration assay, binding to membranes yielded a KDvalue of 45.6 nM and a Bmaxof 0.77 pmol/mg protein. The allosteric modulation data demonstrated that numerous benzodiazepine and barbiturate agents inhibited [3H]SR 95531 binding and this varied according to brain region. Several barbiturates included in the incubation media exhibited a stereoselective inhibition of [3H]SR 95531 binding to whole rat brain membranes. In summary, [3H]SR 95531 identifies the antagonist conformation of GABAAreceptors in the rat brain and binds preferentially to the low‐affinity site. The data collected in the present study show that [3H]SR 95531 is an excellent probe to recognize the GABAAreceptor subtype and allows for the identification of the interactions of subcomponents of the

ISSN:0887-4476    

DOI:10.1002/syn.890020208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe influence of slow muscarinic postsynaptic potentials, i.e., the s‐IPSP and s‐EPSP, on synaptic transmission mediated through nicotinic receptors was studied in the superior cervical ganglion of the rabbit. Postganglionic spikes and synaptic potentials were elicited by delivery of conditioning and test stimulus pulses to afferent fibers. When paired stimulus volleys were separated by brief intervals (20–100 msec) or long intervals (1,000–8,000 msec), the population spike elicited by the test stimulus was larger in amplitude than that elicited by the conditioning volley. When paired stimulus volleys were separated by 250–500 msec, the amplitude of the population spike elicited by the test volley was smaller than that elicited by the conditioning stimulus. Gallamine, which selectively blocks the s‐IPSP, reduced the suppression of the test spike which occurred when stimulus IPIs ranged between 250–500 msec. Pirenzepine, which selectively blocks the s‐EPSP, reduced the late facilitation of test postganglionic spikes which occurred with stimulus IPIs greater than 1,000 msec. The non‐selective muscarinic antagonist QNB, produced changes in postganglionic spike amplitude that were similar to the combined effects of gallamine and pirenzepine. The evidence indicates that the s‐IPSP and s‐EPSP modified the excitability state of the ganglionic neurons and subsequent synaptic transmission that was mediated throug

ISSN:0887-4476    

DOI:10.1002/syn.890020209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890020210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890020201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY