ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Noradrenaline activation of sensory somata that project in damaged peripheral nerves has been postulated to underlie sympathetically-mediated pain. Intracellular recordings from some neurones with myelinated axons in acutely isolated rat dorsal root ganglia showed small prolonged depolarizations to brief applications of 0.1–5 mM noradrenaline whether or not the spinal nerve had been transected. Similar responses were evoked to noradrenaline when phentolamine was present, and also to 1–5 mM catechol, but not 1 mM clonidine, implying the responses were not adrenoceptor-mediated. In extracellular recordings from similar preparations after sciatic transection, many spontaneously active myelinated dorsal root axons were excited by noradrenaline and other sympathomimetics. Silent axons in injured or control ganglia did not respond. Thus, non-specific depolarizations may activate neurones that are hyperexcitable after a lesion but activation of neuronal &agr;-adrenoceptors by sympathetically-released noadrenaline seems unlikely.

ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

A rapid induction of mouseperiod1(mPer1) gene expression is supposed to be critical in the clock gene regulation, especially in the phase resetting of the clock, but its molecular mechanism is poorly understood. Based on the previous finding that the process does not involvede novosynthesis of proteins, we postulated the involvement of CLOCK:BMAL1 heterodimer, a positive regulator of circadian oscillator, in the rapid induction ofmPer1transcription. To test this hypothesis, we utilized CLOCK&Dgr;19, a dominant-negative mutant, to suppress the function of CLOCK:BMAL1in vitro. Serum-evoked rapid increases ofmPer1mRNA expression and promoter activity were significantly blunted when CLOCK:BMAL1 function was interfered with. Furthermore, DNA binding activity of CLOCK:BMAL1 heterodimer to five E-boxes ofmPer1promoter markedly increased shortly after serum shock. Taken together, these results suggest that CLOCK:BMAL1 heterodimer is not only a core component of negative feedback loop driving circadian oscillator, but also involved in the rapid induction ofmPer1during phase resetting of the clock.

ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Converging evidence from animal research and human brain imaging studies, points to an important role of cortical-striatal motor circuitry in the incidental learning of serial order information. To date, attempts to address this role through the study of patients with striatal disorder have proved inconclusive. The present study examined the impact of a therapeutic lesion of the globus pallidus in patients with Parkinson's disease. The lesion, which blocks a primary output of the putamen to the motor cortices, eliminated incidental learning relative both to controls and unoperated patients. The finding offers support for models proposing that context detection within the striatum is a central process in serial order learning. An unexpected effect of the lesion was to significantly reduce the response time to random stimuli relative to an ordered series, the opposite of the normal pattern. It is speculated that this may reflect an unconscious alerting response to novelty, a process suggested to involve the ventral striatum and its cortical targets. Research on Parkinson's disease patients undergoing functional basal ganglia surgery may shed further light on the mechanisms and neuronal substrate of serial order learning in humans.

ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

We have identified a cDNA encoding a novel putative neuron-specific isoform of vacuolar proton-translocating ATPase (V-ATPase), NM9.2, from rat and mouse. Sequence analysis revealed that NM9.2 conserved similar characteristic amino acid sequences with 60–70% identity to M9.2 previously isolated from V-ATPase in chromaffin granules. Using Northern blot analysis, NM9.2 mRNA was specifically detected in the brain, whereas M9.2 mRNA was widely expressed in various tissues.In situhybridization showed that NM9.2 gene expression was restricted mainly to neuronal cells and consistent with that of the a1/Ac116 subunit of V-ATPase. NM9.2 is a putative neuronal isoform of the 9.2 kDa subunit in V-ATPase.

ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Nedd5 is a septin protein enriched in brain and associates with the exocyst complex, a protein complex required for neurite outgrowth in neuroendocrine PC12 cells. In this study, we further investigate the association between Nedd5 and the exocyst complex as well as the role of Nedd5 in neurite outgrowth in differentiating PC12 cells. The endogenous Nedd5 is enriched at the perinuclear region in undifferentiated PC12 cells and radiates outward, from the perinuclear region toward the growth cone, upon NGF-induced PC12 neuronal differentiation. Nedd5, as well as other septin proteins, co-immunoprecipitates with the exocyst complex and tubulin from rat brain lysate. Interestingly, the over-expression of a GTPase-defective Nedd5 mutant promotes aberrant neurite sprouting in PC12 cells. These results demonstrate that Nedd5 and other septin proteins are associated with both the exocyst complex and microtubules and uncover a putative role for the Nedd5 GTPase activity in neurite outgrowth. Taken together, these findings suggest that Nedd5 may be required for polarized neurite outgrowth, perhaps, by facilitating the exocyst complex function during neuronal differentiation.

ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Searching for valid control grafts, we assessed the performance of rats subjected to middle cerebral artery occlusion (MCAO) and grafted with freeze-thawed dead stem cells into sites previously used for active grafts (ipsilateral and contralateral striatum and ventricle) on bilateral asymmetry and water maze tests. We expected to find that sham grafted groups had impairments equivalent to those of MCAO-only controls, relative to intact controls. This proved to be the case for contralateral and intraventricular grafts, and for asymmetry in rats with ipsilateral grafts. However, spatial learning was substantially impaired and lesion volume was increased by 55% with ipsilateral dead cell grafts. Exacerbation of stroke effects indicates potential hazards in the use of dead cells for sham grafts.

ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Hippocampal &agr;4&bgr;&dgr; GABAAreceptors (GABAA-R) are increased following progesterone withdrawal (PWD) in a rodent model of premenstrual anxiety. This &agr;4&bgr;&dgr; receptor isoform uniquely responds to the GABA agonist gaboxadol (THIP) with a maximum current greater than that gated by GABA, and is potentiated more by pentobarbital than are other GABAA-R. We therefore investigated the anxiolytic effects of these drugs using the elevated plus maze. Gaboxadol (1.25 mg/kg) was markedly more anxiolytic in animals undergoing PWD than in controls. Pentobarbital (10 mg/kg) also produced a greater anxiolytic effect during PWD. These results suggest that the pharmacological properties of &agr;4&bgr;&dgr; GABAA-R following PWD are evident behaviorally. Alterations in the &agr;4&bgr;&dgr; GABAA-R population may have implications for the etiology and treatment of premenstrual syndrome.

ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Previous studies suggest that estrogen treatment protects nigrostriatal dopaminergic neurons, but have not examined whether the changes in estrogen levels during estrous cycle can influence the susceptibility of these neurons to neurotoxins. Here we show that the loss of dopaminergic neurons in the substantia nigra was greater in animals lesioned at diestrus (low estrogen) using 6-hydroxydopamine or buffered iron chloride, when compared with animals lesioned at proestrus (high estrogen). Lesioning at diestrus with 6-hydroxydopamine reduced the striatal dopamine content, whereas the dopamine content was preserved in animals lesioned at proestrus. The density of the dopamine transporter, upon which 6-hydroxydopamine toxicity is dependant, was lower when circulating estrogen was high. These results thus support a neuroprotectory role for estrogen.

ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

We studied the neural activation associated with the expectancy of emotional stimuli using whole brain fMRI. Fifteen healthy subjects underwent fMRI scanning during which they performed a warned reaction task using emotional pictures carrying pleasant, unpleasant, or neutral content. The task involved an expected or unexpected condition. Data were analyzed by comparing the images acquired under the different conditions. In the expected condition, compared with the unexpected condition, significant activation was observed in the medial, inferior and dorsolateral prefrontal cortex. Whereas the expectancy of pleasant stimuli produced activation in the left dorsolateral and left medial prefrontal cortex as well as in the right cerebellum, the expectancy of unpleasant stimuli produced activation in the right inferior and right medial prefrontal cortex, the right amygdala, the left anterior cingulate cortex, and bilaterally in the visual cortex. These results suggest that the expectancy of emotional stimuli is mediated by the prefrontal area including the medial, inferior, and dorsolateral prefrontal cortex. Furthermore, our data suggest that left frontal activation is associated with the expectancy of pleasant stimuli and that right frontal activation is associated with the expectancy of unpleasant stimuli. Finally, our findings suggest that the amygdala and anterior cingulate cortex may play an important role in the expectancy of unpleasant stimuli and that the input of this negative information is modulated by these specific brain areas.

ISSN:0959-4965    

出版商:OVID    

年代:2003

数据来源: OVID