摘要:

AbstractThe basal nucleus of Meynert, incorporating the Ch4 group of cholinergic neurons, was examined in six patients with no signs of neurological abnormalities. The ages of the patients ranged from 20 to 80 years. Despite a number of descriptions of these neurons, few age‐related studies have been dedicated to the analysis of the entire anteroposterior extent of the nucleus. Staining with cresyl violet and acetylcholinesterase histochemistry, alone or in combination, was used to identify the cytoarchitectural organization of the Ch4. Computer‐assisted morphometry was used for three‐dimensional visualization and quantitation. The three‐dimensional computer reconstructions revealed a continuous ribbon of neurons with a highly variable density. Four distinct subregions could be clearly identified in all cases by their cytoarchitecture and cellular morphology, although these subgroups were different to those previously described. There were no quantitative differences between the hemispheres in volume, density or cell number of the Ch4, although equivalent levels varied in area and density. The measures were similar in all cases with the exception of the case aged 80 years old. The data demonstrate individual variability in three dimensions and confirm previous studies that found only a mild decline of the Ch4 in old age. © 1993 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890150102

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

年代:1993

数据来源: WILEY

摘要:

AbstractC‐terminals can be distinguished at the ultrastructural level from other types of nerve endings on motoneurons by their prominent and regularly occurring postsynaptic specializations termed subsurface cisterns (SSC). We have previously shown (Yamamoto et al., 1991) that an antibody directed against a sequence within the gap junction protein connexin 32 immunolabels these motoneuronal SSCs and can therefore serve as a immunohistochemical tool to visualize indirectly the location of C‐terminals on motoneurons at the light microscope level. Here we have used this anti‐SSC antibody in combination with antibodies against choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) to determine whether C‐terminals on motoneurons contain these cholinergic enzyme; markers. In sections at all major spinal cord levels and in several cranial motor nuclei examined, motoneuronal cell bodies and their proximal dendrites were studded with large ChAT‐immunoreactive (ChAT‐IR) boutons. Boutons having a similar distribution and appearance on motoneurons were also immunolabelled for AChE. In addition, motoneurons were surrounded by a dense plexus of AChE‐immunoreactive (AChE‐IR) varicose fibers and fine preterminal axons. In double‐labeled sections, AChE‐IR boutons corresponded to those immunolabeled for ChAT. In sections processed for simultaneous immunofluorescence detection of ChAT and SSCs, ChAT‐IR boutons were very often found in apposition to immunolabeled SSCs. In sections processed for simultaneous labeling of AChE and SSCs, AChE‐IR boutons were again frequently seen abutting labeled SSCs. These results provide the first strong evidence at the LM level that a large proportion, if not the entirety, of C‐terminals are cholinergic and show that these terminals consist in part of relatively large varicosities along highly varicose axons that form en passant type contacts on motoneurons. At the same time, our results substantially narrow possibilities regarding the as yet undetermined source of C‐terminals, which can now be considered to originate from cholinergic neurons, such as those located in the brainstem and/or the spinal c

ISSN:0887-4476    

DOI:10.1002/syn.890150103

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

年代:1993

数据来源: WILEY

摘要:

AbstractRepeated daily cocaine injections have been shown to alter μ‐opioid receptor densities in the caudate putamen and nucleus accumbens of rat brain (Unterwald et al., 1991, 1992). Addenylyl cyclase activity was measured in rat rostral caudate putamen and nucleus accumbens following repeated cocaine administration to determine the functional consequences of cocaine‐induced opioid receptor changes. Male Fischer rats were injected daily for 14 days with saline or cocaine HC1 (30 or 45 mg/kg/day, i.p.) in three equal doses at 1‐hr intervals. Basal adenylyl cyclase activity and the effects of the selective μ‐ and δ‐opioid agonists [D‐Ala2, N‐Me‐Phe4, Gly‐ol5]enkephalin (DAMGO) and [D‐penicillamine2, D‐Penicillamine5]enkephalin (DPDPE), respectively, on arenylyl cy‐clase activity were examined 30 min after the last injection using a cAMP radioligand binding assay in crude membrane preparations. Basal adenylyl cyclase activity was 49% and 34% lower in the caudate putamen of animals treated with 30 and 45 mg/kg/day of cocaine, respectively, as compared to those receiving saline injections. Basal adenylyl cyclase activity was unchanged in the nucleus accumbens following cocaine treatment. DAMGO and DPDPE each maximally inhibited approximately 25% and 30%, respectively, of basal adenylyl cyclase in the caudate putamen and nucleus accumbens of saline‐injected animals. Administration of cocaine attenuated the ability of DPDPE to inhibit adenylyl cyclase in both brain regions, but had no effect on the efficacy or potency of DAMGO for inhibiting adenylyl cyclase activity. These results suggest that chronic, repeated cocaine administration results in a selective impairment of δ‐opioid receptor‐mediated effector function in the caudate putamen and nucleus

ISSN:0887-4476    

DOI:10.1002/syn.890150104

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

年代:1993

数据来源: WILEY

摘要:

AbstractOf the five cloned muscarinic receptor subtypes, dopamine (DA) neurons in the substantia nigra and ventral tegmental areas have been shown to be selectively enriched with the mRNA: for the m5 subtype, suggesting that muscarinic modulation of DA neurons may have a distinct pharmacology. In the present study we have used dissociated cell cultures of fetal rat ventral mesencephalon to characterize muscarinic modulation of DA neurons. [3H]DA release stimulated by activation of N‐methyl‐Daspartate (NMDA) receptors was potentiated by carbachol, a mixed muscarinic‐nicotinic agonist, and by oxotremorine‐M, a muscarinic agonist. Neither carbachol nor oxotremorine‐M had an effect on [3H]DA release evoked by the non‐NMDA agonists, kainate or quisqualate. A nicotinic agonist, DMPP, had no effect on NMDA‐stimulated release. Potentiation of NMDA‐stimulated [3H]DA release by oxotremorine‐M was inhibited by the broad spectrum muscarinic antagonist, QNB, and by low concentrations of a putative Ml antagonist, pirenzepine, while much higher concentrations of a purported M2 antagonist, AF‐DX 384, were required to reverse the oxotremorine‐M effect. The muscarinic antagonist, 4‐DAMP, was active in a concentration range between that required for pirenzepine and AF‐DX 384. Further experiments examined intracellular messenger mechanisms coupled to the muscarinic receptors modulating NMDA‐stimulated [3H]DA release. In contrast to oxotremorine‐M, two muscarinic agents with only weak partial agonism with respect to phosphoinositide turnover, pilocarpine and arecoline, had no effect on NMDA‐stimulated [3H]DA release. Potentiation of NMDA‐stimulated [3H]DA release by oxotremorine‐M was inhibited by staurosporinc, an inhibitor of protein kinase C, but was unaffected by H8, an inhibitor of cAMP‐ and cGMP‐dependent protein kinases. Pretreatment of cultures with pertussis toxin did not alter oxotremorine‐M potentiation of the NMDA response. Our results indicate that the muscarinic receptors responsible for potentiation of NMDA‐stimulated [3H]DA release in mesencephalic cultures are linked to phosphoinositide hydrolysis and protein kinase C activation via pertussis toxin insensitive G proteins. The data are also consistent with the identification of these receptors as the m5 subtype of cloned receptor, on the basis of the relative potency of muscarinic agonists and antagonists in this system, although involvement of ml receptors cannot be excluded solely on this basis. Taken together with previous reports showing selective localization of m5 receptor mRNA in regions containing DA cell bodies, these studies suggest that use of dissociated cell cultures may thus be an appropriate model for studying direct modulation of dopaminergic neurons by cholinergic agents interacting with pu

ISSN:0887-4476    

DOI:10.1002/syn.890150105

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe present study aimed to localize and characterize [125I‐Tyr8]‐BK binding sites in all major segments of the guinea pig spinal cord using in vitro quantitative receptor autoradiography. [125I‐Tyr8]‐BK specific binding sites were localized predominantly in superficial layers of the dorsal horn, with lamina II depicting the highest labelling. The density of specific binding in laminae I and III was moderate, whereas in other areas, i.e., laminae IV‐X, lower amounts of labelling were noticed. The B2receptor antagonists D‐Arg[Hyp3,Thi5,D‐Tic7,Oic8]‐BK (Hoe 140),D‐Arg[Hyp3,D‐Phe7,Leu8]‐BK,Tyr0,D‐Arg[Hyp3,D‐Phe7,Leu8]‐BK, D‐Arg[Tyr3,D‐Phe7,Leu8]‐BK, D‐Arg[Hyp2,Thi5.8,DPhe7]‐BK, D‐Arg[Hyp3,Leu8]‐BK and D‐Arg[Hyp3,Gly6,Leu8]‐BK as well a., unlabelled [Tyr8]‐BK inhibited [1251‐Tyr8]‐BK binding with respective Ki values of 0.04, 12.4, 23.4, 34.5, 43.5, 33.5, 23.0, and 0.6 nM while B1related molecules (Tyr0, des‐Arg10‐kallidin and [Leu8]‐des‐Arg9‐BK) did not significantly inhibit [125I‐Tyr8]‐BK binding up to micromolar concentrations. These results indicate that the specific [125I‐Tyr8]‐BK binding sites present in the guinea pig spinal cord belong to the B2 receptor subtype. The high density of B2binding sites in the substantia gelatinosa provides an anatomical evidence in favour of a role for

ISSN:0887-4476    

DOI:10.1002/syn.890150106

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

年代:1993

数据来源: WILEY

摘要:

AbstractMPP+(1‐methyl‐4‐phenylpyridinium), a dopaminergic neurotoxin that provides the best available experimental model of Parkinson's disease, is selectively concentrated in dopamine neurons by the dopamine transporter (DAT). DAT also serves as a primary recognition site for cocaine. To help define selective molecular mechanisms by which MPP+uptake occurs, we have tested dopamine transporters mutated in several residues for their abilities to accumulate dopamine and MPP+, and to bind a cocaine analog. Mutants in DAT 7th and 11th hydrophobic putative transmembrane domains increase MPP+uptake velocity and affinity (1/KD), respectively. These mutations exert much more modest effects on dopamine uptake and have little impact on cocaine analog binding. These findings provide the first example of mutations that enhance transport and identify specific DAT amino acids selectively involved in neurotoxin uptake. They may also have implications for the feasibility of developing drugs that could specifically block accumulation of Parkinsonism‐inducing neurotoxins. © 1993 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890150107

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe 5‐hydroxytryptamine (5HT) containing bulbospinal pathway was studied with immunohistochemical (IF) and chemical techniques in 2–3 and 30 months old male Sprague‐Dawley rats. The coexisting neuropeptides substance P (SP), thyrotropin‐releasing hormone (TRH) and galanin were also analysed. Furthermore, the expression of mRNA encoding aromatic L‐amino acid decarboxylase (AADC), prepro‐TRH, and preprotachykinin (prepro‐SP) was analysed with in situ hybridization (ISH) in the midline raphé nuclei in the lower brainstem.The results showed a decreased number of axonal 5HT fibers with a normal morphology in the ventral horn of the aged rat lumbosacral spinal cord, and several 5HT immunoreactive (IR) fibers with an aberrant morphology, suggestive of axonal degeneration, were intermingled. This was evident in both the dorsal and ventral horn of the spinal cord. The 5HT‐IR fibers with an aberrant morphology usually also contained TRHand/or SP‐ and/or galanin‐like immunoreactivity (LI) in the ventral horn. These signs of degeneration were clearly less evident in the thoracic and cervical spinal cord segments. Moreover, these changes varied between aged litter‐mates. This was in agreement with behavioural signs of motor disturbances, present in about 40% of the aged rats and which in all cases were confined to the hindlimbs.Chemical analyses disclosed significantly lower levels of TRH‐LI and, in particular, SP‐LI in both the ventral and dorsal quandrants of the spinal cord in the aged rat compared to young adults. The differences were largest in the lumbar regions of the spinal cord. Corresponding analysis of 5HT and 5‐hydroxyindoleacetic acid (5HIAA) in the same tissue specimens revealed largely unaltered levels of 5HT and a slight increase in 5HIAA, indicating the possibility of an increased 5HT turnover in the aged rat spinal cord.Neurons in nucleus raphé obscurus and nucleus raphé pallidus were immunoreactive to 5HT, and after pretreatment with colchicine to TRH‐, SP‐, and galanin‐LI as well. There was no obvious difference in number of labeled cells, or labeling intensity, between colchicine‐treated young adult and aged rats, although, in the corresponding region of medulla oblongata, chemical analysis disclosed significantly lower levels of 5HT, TRH, and, in particular, SP in untreated aged rats. In contrast, in situ hybridization analysis revealed increased mRNA levels encoding prepro‐TRH and prepro‐SP in old rats, while mRNA content encoding AADC mRNA was similar in young adult and aged rats.The results demonstrate an age related degeneration of the 5HT axon arborizations in the spinal cord with a clear rostrocaudal variance correlated to the motor deficiences observed in the aged rat. Aberrant axons often also contained TRH, SP, and galanin. The marked decline in spinal TRH and SP combined with the increase levels of medullary SP and TRH mRNA suggest increased peptide turnover in the aged, rat. There was also indications for an increased 5HT turnover. Finally, chemical results showed that local and/or primary afferent peptide systems in the dorsal horn may be affect

ISSN:0887-4476    

DOI:10.1002/syn.890150108

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

年代:1993

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890150109

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

年代:1993

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890150110

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

年代:1993

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890150101

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

年代:1993

数据来源: WILEY