摘要:

LITTLE is known about the molecular organization and functions of the postsynaptic density (PSD), a cytoskeletal specialization on the postsynaptic membrane. In an attempt to elucidate the protein composition of PSD, we have sequenced a 35 kDa protein of the rat forebrain PSD fraction. Amino acid sequence information of the tryptic peptides and immunoblot analyses revealed that the protein is a voltage-dependent anion channel 1 (VDAC1). VDAC1 was enriched in the PSD fraction and was partially soluble in 1% n-octyl glucoside (NOG) or Triton X-100. Our data indicate that VDAC1, which is originally found in the outer mitochondrial membrane, is also present in the central nervous system (CNS) synapses in association with the PSD ‘core’.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

THE role of spinal NMDA receptors in mechanical nociceptive processing was assessed in sheep. Intrathecal NMDA (2 nmol–1 μmol) produced a significant reduction in mechanical withdrawal thresholds. This effect was attenuated by pretreatment with the NMDA receptor antagonist MK801 (100 nmol), the cyclooxygenase-2 (COX-2) inhibitor 5,5-dimethyl-3-(3-flourophenyl)-4-(4-methylsulphonyl)phenyl-2(5H) furanone DFU; 200 nmol) and the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 2 μmol), but not by the metabotropic glutamate receptor antagonist (S)-α-methyl-4-carboxyphenylglycine (MCPG; 200 nmol-2 μmol) or the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 200 nmol-1 μmol). This first report of NMDA-induced mechanical allodynia suggests that spinal NMDA receptors are involved in mediating acute mechanical nociceptive processing through activation of NOS and COX-2 enzymes.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ALTHOUGH there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SATURATION analyses of [3H]L-689,560, [3H]CGP 39653 and NMDA-specific [3H]ifenprodil binding revealed an equivalent increase (0.7 pmol/mg) in the number of [3H]L-689,560 and [3H]ifenprodil binding sites in superior temporal cortex (BA22) from drug-treated chronic schizophrenic patients and control subjects. No differences were observed between control and schizophrenic subjects for [3H]CGP 39653 binding in BA22, or for any of the radioligands binding to pre-motor cortex (BA6). Since [3H]L-689,560, [3H]CGP 39653 and [3H]ifenprodil label the glycine, glutamate and ifenprodil sites of the NMDA receptor complex, which are associated with NR1, NR1/NR2A and NR1/NR2B subunits respectively, our findings suggest that NR2B-containing receptors are selectively up-regulated in superior temporal cortex in schizophrenia.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

INTRACELLULAR activity of the slow adapting neurone (SAN) was recorded together with extracellular action potentials (APs) of SAN, fast adapting neurone and inhibitory fibre in the isolated stretch receptor of the moulting crayfish. Following strychnine application, spontaneous APs and seizure-like AP trains were observed. A delay of the inhibitory fibre APs relative to SAN inhibitory postsynaptic potential, their waveforms and their initiation by intracellular SAN hyperpolarization indicate that their generation was close to the inhibitory nerve terminal. Such antidromic (ectopic) APs assert their postsynaptic action on both receptor neurones via the axon reflex. The findings provide first evidence of antidromic APs generated in the vicinity of inhibitory terminals, their direct and axon reflex-mediated action on target neurones and support a hypothesis that increased terminal excitability contributes to seizure activity.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

THE membranous labyrinth of the guinea pig cochlea and retrocochlear neural structures were investigated by magnetic resonance imaging (MRI) using an experimental system with a field strength of 4.7 T and a single turn surface coil 25 mm in diameter, or standard resonators of 34 or 70 mm in diameter and gradient field strengths of 950 mTm and 200 mTm. High-resolution 2-D and 3-D images of 0.3–1.0 mm slice thickness were acquired by a rapid acquisition with relaxation enhancement (RARE) sequence and a standard multiecho technique. Structural and dimensional aspects of the cochlea were resolvedin vitroandin vivodown to < 50 μm, showing the scala vestibule, scala media, scala tympani, spiral ganglia and the cochlear (eighth) nerve.In vivoperfusions with the gadodiamide (GdDTPABMA) chelate-bound paramagnetic gadolinium ion resulted in dynamic temporal enhancement of the scala vestibule and scala tympani, but did not penetrate the scala media.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

WE examined the temporal modulation of intracellular calcium release channels in the suprachiasmatic nucleus (SCN). We found a circadian rhythm in [3H]ryanodine binding that was specific to the SCN. The peak in the rhythm occurred at CT 7 and was due to an increase in Bmax, which correlated well with immunoblots showing an increase in RyR-2 expression in the SCN. Double immunohistochemical studies showed that RyR-2 was expressed exclusively in neurons. Ryanodine and caffeine applied around CT 7–9 advanced the clock phase in a hamster brain slice preparation. No rhythm of IP3R was seen in any of the brain areas studied. Our results indicate that RyR-2 exhibits an endogenous rhythm, which influences the intracellular calcium dynamics and thus modulates SCN activity.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

WE found a new mutation in the GTP cyclohydrolase gene involved in dopa-responsive dystonia. We sequenced the GTP cyclohydrolase gene in a family with four siblings affected by this disorder and identified an A–T mutation in exon 2, leading to a non conservative amino acid substitution at codon 135 of the protein (Ile135Lys), which may change the conformation of the binding site of this enzyme. The clinical evolution was heterogeneous among carriers of the same mutation, underlining the involvement of other determinants modulating the occurrence of the disease such as genetic or environmental susceptibility factors.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

RAT dopamine D2shortreceptors expressed in CHO cells were characterized by activation of [35S]GTPγS binding. There were no significant differences between the maximal effects seen in activation of [35S]GTPγS binding caused by dopaminergic agonists, but the effects of 5-HT, 8OH-DPAT and 5-methoxytryptamine amounted to 47 ± 7%, 43 ± 5% and 70 ± 7% of the dopamine effect, respectively. The dopaminergic antagonist (+)butaclamol inhibited activations of both types of ligands with equal potency (pA2= 8.9 ± 0.1), indicating that only one type of receptor is involved. In competition with [3H]raclopride binding, dopaminergic agonists showed 53 ± 2% of the binding sites in the GTP-dependent high-affinity state, whereas 5-HT showed only 20 ± 3%. Taken together, the results indicate that serotonergic agonists behave as typical partial agonists for D2receptors with potential antiparkinsonian activity.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

WE report a Japanese family with early onset hereditary frontotemporal dementia and a novel missense mutation (Ser305Asn) in the tau gene. The patients presented with personality changes followed by impaired cognition and memory as well as disorientation, but minimal Parkinsonism. Imaging studies showed fronto-temporal atrophy with ventricular dilatation more on the left, and postmortem examination of the brain revealed numerous neurofibrillary tangles (NFTs) with an unusual morphology and distribution. Silver-stained sections showed ring-shaped NFTs partially surrounding the nucleus that were most prominent in frontal, temporal, insular and postcentral cortices, as well as in dentate gyrus. Cortical NFTs were restricted primarily to layer II, and were composed of straight tubules. Numerous glial cells containing coiled bodies and abundant neuropil threads were detected in cerebral white matter, hippocampus, basal ganglia, diencephalon and brain stem, but no senile plaques or other diagnostic lesions were seen. Both the glial and neuronal tangles were stained by antibodies to phosphorylation-independent and phosphorylation-dependent epitopes in tau. Thus, this novel mutation causes a distinct familial tauopathy.

ISSN:0959-4965    

出版商:OVID    

年代:1999

数据来源: OVID