摘要:

AbstractThe distribution of enkephalin (ENK)‐like immunoreactivity (LI) in spinal cord and medulla oblongata of cat and gray monkey (Macaca fascicularis) was studied by use of immunofluorescence and peroxidase antiperoxidase (PAP)techniques. Possible coexistence between ENK‐ and 5‐hydroxytryptamine (5‐HT)‐LI was also analyzed with double labeling immunofluorescence. Furthermore, in situ hybridization was used to demonstrate cell bodies in the brain stem expressing mRNA encoding for ENK.ENK‐immunoreactive (IR) axonal varicosities and fibers were demonstrated throughout the spinal cord gray matter, with the highest density in the superficial dorsal horn, the area around the central canal, the intermediolateral cell column, the sacral parasympathetic nucleus, and in Onuf's nucleus. In the monkey ventral horn, ENK‐IR varicose fibers could in some cases be demonstrated in very close apposition to cell bodies. A low degree of co‐localization between ENK‐ and 5‐HT‐LI was seen in the spinal cord of both species. Still, fibers containing both compounds could as a rule be demonstrated in every section studied. The highest degree of coexistence was encountered in the motor nucleus of the ventral horn. Six weeks after a low thoracic spinal cord transection a decreased staining for ENK‐LI was demonstrated in the ventral horn motor nucleus, whereas other parts of the spinal cord appeared unaffected.In the brain stem of cats after colchicine treatment, ENK‐LI was found in a majority of the 5‐HT‐IR cell bodies in the raphe nuclei (nucleus raphe magnus, pallidus and obscurus) and in the lateral reticular nucleus (rostroventrolateral reticular nucleus). In cat not pretreated with colchicine, a few weakly stained ENK‐IR cell bodies could be found in the midline raphe nuclei and in the lateral reticular nucleus with the PAP technique. In the monkey brain stem without colchicine treatment, using the PAP technique, heavily stained ENK‐IR cell bodies could be seen in the lateral reticular nucleus while no convincing mRNA signal could be found over cell bodies in the raphe nuclei.It is concluded that part of the ENKergic innervation of the cord in both species derives from supraspinal or suprasegmental levels. In the cat there is a discrepancy between the low degree of coexistence with 5‐HT observed in terminals in the spinal cord and the extensive coexistence in presumed cell bodies of origin in the medulla of colchicine treated animals. One possible explanation for this is that the expression of ENK in raphe neurons under normal circumstances is very low but that colchicine induces an upregulation of the synthesis

ISSN:0887-4476    

DOI:10.1002/syn.890110202

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

年代:1992

数据来源: WILEY

摘要:

AbstractThis brief review discusses the recent characterization in the brain of a gene coding for a protein that may be involved in programmed cell death and/or brain plasticity. We will term it sulfated glycoprotein‐2 (SGP‐2), the name corresponding to the first cDNA characterized. Recent studies have demonstrated the overexpression of this sulfated glycoprotein in various CNS disorders, such as certain gliomas, Alzheimer's disease and epilepsy, as well as after experimental brain injury in animals where different cell types were undergoing tissue remodelling or cell death. In peripheral tissues, SGP‐2 gene expression has been found to be strikingly increased following experimental manipulations in which cells of injured tissues were undergoing programmed cell death or apoptosis. The results reported thus far are intriguing and suggest the possible involvement of SGP‐2 in apoptotic mechanisms as well as its interaction with components of the immune system possibly associated with cell death in neurodegenerative disorders. © 1992 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890110203

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

年代:1992

数据来源: WILEY

摘要:

AbstractRepeated cocaine intoxication can result in the development of behavioral sensitization in animals and psychosis in humans, phenomena that have been associated with alterations in dopamine (DA) function. Using electrophysiologic and autoradiographic techniques, modifications of central serotonin (5‐hydroxytryptamine; 5‐HT) systems were investigated in rats treated with a regimen of cocaine administration that produced behavioral sensitization. The inhibitory response of single 5‐HT neurons in the dorsal raphe (DR) to (−)‐cocaine, the 5‐HT uptake inhibitor fluoxetine or the 5‐HT1Aagonist 8‐hydroxy‐2‐[di‐N‐propylamino]tetralin (8‐OHDPAT) was significantly enhanced in cocaine‐treated rats. Furthermore, several brain areas that contain either cell bodies (DR) or terminals for 5‐HT (medial and sulcal prefrontal cortex, frontal cortex) showed cocaine‐induced elevations in [3H]imipramine‐labeled 5‐HT uptake sites, while [3H]‐8‐OHDPAT‐labeled 5‐HT1Areceptors were decreased only in the central medial amygdala. These results suggest that modifications of autoregulatory mechanisms secondary to alterations of 5‐HT uptake processes may contribute to the developmen

ISSN:0887-4476    

DOI:10.1002/syn.890110204

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe neurotransmitter γ‐aminobutyric acid (GABA) is present in efferent neurons of the striatum and of the pallidum, one of the main striatal target areas. Dopaminergic nigrostriatal neurons play a critical role in the regulation of GABAergic neurotransmission in the striatum. In the present study, we investigated their role in the regulation of glutamate‐decarboxylase (GAD) mRNA expression in two divisions of the pallidum in rats: the globus pallidus and entopeduncular nucleus, equivalent to the external and internal pallidum, respectively, of primates. Dopaminergic neurons were lesioned by unilateral injections of 6‐hydroxydopamine (6‐OHDA) in the substantia nigra of adult rats. Two or 3 weeks after the lesion, frontal cryostat‐cut sections of the brain were processed for in situ hybridization histochemistry with35S‐labeled RNA probes synthesized from cDNAs encoding two distinct isoforms of GAD of respective molecular weight 67,000 (GAD67) and 65,000 (GAD65). The number of labeled cells was determined, and intensity of labeling in individual cells was analyzed by computerized image analysis on emulsion radioautographs.In the globus pallidus, the number of labeled neurons and intensity of labeling per cell were increased on the side ipsilateral to the lesion as compared with control rats in sections hybridized with the GAD67 RNA probe. No changes were detected on the side contralateral to the lesion or in the levels of labeling for GAD65 mRNA. Confirming previous data, the level of labeling for GAD65 mRNA was much higher than for GAD67 mRNA in the entopeduncular nucleus of control rats. In rats with a 6‐OHDA lesion, labeling for both GAD67 and GAD65 mRNAs was decreased on the side contralateral, but not ipsilateral, to the lesion, as compared with control rats.The results show that lesions of the nigrostriatal pathway in rats affect the levels of mRNAs encoding two distinct isoforms of GAD in neurons of the globus pallidus and entopeduncular nucleus differently. In addition, results in the entopeduncular nucleus further support a bilateral effect of unilateral dopaminergic lesions. © 1992

ISSN:0887-4476    

DOI:10.1002/syn.890110205

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

年代:1992

数据来源: WILEY

摘要:

Abstract[123I]RTI‐55, an iodinated derivative of the cocaine analog 3β‐phenyltropane‐2β‐carboxylic acid methyl ester, was evaluated as an agent for in vivo labeling of the serotonin transporter. Labeling of the precursor of RTI‐55 with I‐123 was efficient and yielded a high specific activity product. After intravenous injection of [123I]RTI‐55 into rats, the tracer accumulated in regions with high densities of serotonin and dopamine uptake sites. The distribution of [123I]RTI‐55 binding in areas rich in serotonin uptake sites correlated with [3H]serotonin uptake measured in vitro in the same regions. Specific [123I]RTI‐55 binding to serotonin uptake sites was inhibited by paroxetine but not by GBR 12,909. Treatment of rats with neurotoxic doses of fenfluramine caused decreases of 66% (in the hypothalamus) to 83% (in the superior colliculi) of specific [125I]RTI‐55 binding in all areas except in the striatum and the olfactory tubercles (regions rich in dopamine transporters). These results indicate that [123/125I]RTI‐55 binds, although not selectively, to the serotonin transporter in vivo. Furthermore, they suggest that [123I]RTI‐55 holds promise as a SPECT imaging agent for the study of the serotonin transporter in humans in health and disease.

ISSN:0887-4476    

DOI:10.1002/syn.890110206

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

年代:1992

数据来源: WILEY

摘要:

AbstractCalcium‐dependent protein phosphorylation may be a critical step in the stimulated secretion of anterior pituitary hormones. We have noted the existence of a number of calcium‐calcium/calmodulin‐, and calcium/phospholipid‐dependent phosphoproteins in the normal rat anterior pituitary. Cell extracts were prepared from anterior pituitary glands of male rats and phosphorylated with [γ32P]ATP in the presence or absence of calcium, calmodulin, and phosphatidylserine. The samples were electrophoresed on SDS‐PAGE gels, autoradiographs prepared, and phosphate incorporation into specific proteins quantitated with microdensitometry. Calcium alone significantly stimulated the phosphorylation of proteins with molecular weights of 80.0‐, 62.0‐, 51.0,‐ 30.5‐, and 25.0‐kDa. The phosphorylation of 21.5‐, 51.0‐, and 80.0‐kDa MW phosphoproteins was found to be phospholipid dependent. The phosphorylation of 62.0‐, 51.0‐, 33.0‐, 30.5‐, and 25.0‐kDa MW phosphoproteins was found to be calcium/calmodulin kinase dependent. Calcium/calmodulin also inhibited phosphorylation of the 80.0

ISSN:0887-4476    

DOI:10.1002/syn.890110207

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe distribution of D1and D2dopamine (DA) receptors in the nuclei and subnuclear zones of the rat amygdaloid complex was mapped using quantitative light microscopic autoradiography. [125I]iodosulpiride and [125I]SCH 23982 (in the presence of 50 nM ketanserin) were used to label D2and D1DA receptors, respectively. The DA receptor subtypes exhibited a topographic, nonoverlapping distribution which generally conformed to the cytoarchitectonic boundaries of the component nuclei and subnuclear zones of the amygdaloid complex. The highest density of [125I]iodosulpiride binding sites was observed in the main intercalated cell group and the central amygdaloid nucleus where a medial to lateral gradient of binding sites was localized to its subnuclear zones. [125I]SCH 23982 binding sites were localized in the main intercalated cell group and the basolateral amygdaloid nucleus with a uniform low density in the central nucleus. The functional topography of mesoamygdaloid DA neurons may therefore be mediated, in part, at the level of DA receptor subtypes. The pattern of distribution of [125I]iodosulpiride binding sites in subdivisions of the central amygdaloid nucleus and bed nucleus of the stria terminalis suggests that the functions of the “extended amygdala,” a major system of the functional organization of the basal forebrain, may be regulated by DA afferents at multiple key sites of D2receptor action. © Wiley‐Lis

ISSN:0887-4476    

DOI:10.1002/syn.890110208

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

年代:1992

数据来源: WILEY

摘要:

AbstractRepeated administrations of methamphetamine (m‐AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N‐methyl‐D‐aspartate (NMDA) receptors has been shown previously to prevent m‐AMPH‐induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK‐801 on m‐AMPH‐induced striatal DA overflow. Four injections of MK‐801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m‐AMPH (4.0 mg/kg, sc at 2‐hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m‐AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK‐801 15 min before each of the four m‐AMPH injections or prior to only the last two m‐AMPH administrations attenuated the m‐AMPH‐induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK‐801 treatment regimens less effectively reduced the m‐AMPH‐induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = −.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m‐AMPH is a crucial component of the subsequent neurotoxicity. Blockade of NMDA receptors with MK‐801 apparently prevents damage to DA neurons by attenuating this s

ISSN:0887-4476    

DOI:10.1002/syn.890110209

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe response of extracellular norepinephrine to the acute administration of amphetamine was assessed, using dialysis, in prefrontal cortex and hippocampus in awake, behaving rats. Norepinephrine exhibited a pronounced and rapid dose‐ and time‐dependent increase in response to 0.5 and 2.5 mg/kg amphetamine, which corresponded closely to the time course of the behavioral profile. These results are consistent in with a possible role for norepinephrine in the behavioral response to amphetamine. © Wiley‐Lis

ISSN:0887-4476    

DOI:10.1002/syn.890110210

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

年代:1992

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890110201

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

年代:1992

数据来源: WILEY