Effects of lamotrigine on field potentials and long-term potentiation in guinea pig hippocampal slices

PURPOSE: To investigate the effects of lamotrigine (LTG), a new anticonvulsant, on neuronal excitability, synaptic transmission, and long-term potentiation (LTP) in guinea pig hippocampal slices. METHODS: Electrically evoked field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) were investigated in the CA1 region of the hippocampus. RESULTS: The concentration-response curves showed different actions of LTG in concentrations near therapeutic plasma levels (10 microM) on fEPSPs and PSs. The initial slopes of fEPSPs were not affected, whereas the amplitudes of PSs were significantly decreased. Higher concentrations of LTG decreased both fEPSP slopes and PS amplitudes; however, the effects on PSs were much stronger. Also, there were no differences in fEPSP slopes or PS amplitudes compared with controls when LTP was induced in the presence of LTG (10 microM). CONCLUSIONS: Our data are in contrast to previous findings that suggest LTG acts primarily on presynaptic sites by blocking the release of excitatory amino acids. Further, LTP was not affected by LTG.     

Comparative study of event-related potentials and positron emission tomography activation during a paired-associate memory paradigm

Event-related potentials (ERP) and regional cerebral blood flow (rCBF) activation using ¹⁵O-labeled water associated with retrieval and retention of episodic memory were studied during a visual paired-association task with delayed response in eight healthy subjects. In both studies, the subjects memorized four pairs of figures during the learning period. They were presented with each cue (S1) and asked to judge whether the following figure (S2) formed one of the memorized pairs. In an attempt to identify brain activity related to memory function, a choice reaction task with delay was used as a behavioral control. The ERP study showed a posterior positive component in the difference waveform, which was obtained by subtracting responses in the choice reaction task from those in the paired association task, between 300 and 850 ms after S1 presentation. It was maximal at the parietal midline electrode and distributed predominantly over the left posterior quadrant of the scalp. The rCBF activation study showed a greater increase in rCBF in the right dorsolateral prefrontal cortex (Brodmann’s area 46), left inferior frontal cortex (Brodmann’s area 44/45), left thalamus, and bilateral cerebellar hemisphere during the paired association task as compared to the choice reaction task, which suggests a possible involvement of cerebello-thalamo-cortical circuit in the memory processing. Additionally, it is suggested that the scalp distribution of the ERP component may not necessarily represent regional cortical activation below the electrodes where such a component is observed and could indirectly represent activation in remote areas such as subcortical regions. It seems that ERP and rCBF activation may provide information about different aspects of higher brain function. Received: 19 July 1996 / Accepted: 22 August 1997     

The recovery function of paired somatosensory evoked potentials in cerebral ischemic rabbits

In cerebral ischemia of different degrees, the amplitudes of somatosensory evoked potentials (SEPs) are facilitated or depressed. Different mechanisms might be responsible for the explanation of the contradictory phenomena. SEPs obtained using the paired stimulation method were employed in trying to find out the role of the functional changes of the inhibitory system in the brain during ischemia. Eight rabbits were used for recording the amplitude recovery curve of paired SEPs in the normal state, and the other ten were used for recording the recovery curve in different cerebral ischemic degrees. Cerebral ischemia was induced by the iron particle injection method. The attenuation of the depressed recovery function of the paired SEP amplitudes was detected during cerebral ischemia when SEP amplitudes were either facilitated or depressed. The results indicate that the function of the inhibitory system in the brain is selectively vulnerable during cerebral ischemia.     

Neural correlates of encoding and expression in implicit sequence learning

It has been shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) to the human primary motor hand area (M1-HAND) can induce a lasting increase in corticospinal excitability. Here we recorded motor evoked potentials (MEPs) from the right first dorsal interosseus muscle to investigate how sub-threshold high-frequency rTMS to the M1-HAND modulates cortical and spinal excitability. In a first experiment, we gave 1500 stimuli of 5 Hz rTMS. At an intensity of 90% of active motor threshold, rTMS produced no effect on MEP amplitude at rest. Increasing the intensity to 90% of resting motor threshold (RMT), rTMS produced an increase in MEP amplitude. This facilitatory effect gradually built up during the course of rTMS, reaching significance after the administration of 900 stimuli. In a second experiment, MEPs were elicited during tonic contraction using weak anodal electrical or magnetic test stimuli. 1500 (but not 600) conditioning stimuli at 90% of RMT induced a facilitation of MEPs in the contracting FDI muscle. In a third experiment, 600 conditioning stimuli were given at 90% of RMT to the M1-HAND. Using two well-established conditioning-test paradigms, we found a decrease in short-latency intracortical inhibition (SICI), and a facilitation of the first peak of facilitatory I-waves interaction (SICF). There was no correlation between the relative changes in SICI and SICF. These results demonstrate that subthreshold 5 Hz rTMS can induce lasting changes in specific neuronal subpopulations in the human corticospinal motor system, depending on the intensity and duration of rTMS. Short 5 Hz rTMS (600 stimuli) at 90% of RMT can selectively shape the excitability of distinct intracortical circuits, whereas prolonged 5 Hz rTMS (900 stimuli) provokes an overall increase in excitability of the corticospinal output system, including spinal motoneurones.     

The contribution of adrenergic mechanisms to frequency potentiation and to paired stimulation in guinea pig isolated atrial tissue

Summary In order to establish whether adrenergic mechanisms are involved in frequency induced potentiation and in the positive inotropic response to paired stimulation, the effect of adrenergic drugs on both processes were studied in guineapig isolated left auricles. 1. Owing to the positive inotropic effect of noradrenaline and isoproterenol the relative increase in contractile force at rising frequencies proved less pronounced than in control experiments, although the absolute maximal force that developed was higher in presence of the sympathomimetic drugs. 2. Pretreatment of the guinea-pigs with high doses of reserpine did not impair both potentiation phenomena in the isolated organs. Surprisingly, frequency potentiation proved even slightly increased in the noradrenaline-depleted organs. 3. A low concentration of propranolol (10^–9 M) did not affect both potentiation phenomena. Propranolol, in such concentration (10^–6 M) that unspecific, quinidine-like effects occurred diminished both frequency potentiation and the response to paired stimulation. 4. The results suggest that adrenergic mechanisms do not play any significant role in both potentiation phenomena.     

Neuritic plaques in the Lewy body variant of Alzheimer disease lack paired helical filaments

The Lewy body variant of Alzheimer disease (LBV) is a distinct category of dementia which, unlike pure diffuse Lewy body disease (DLBD), meets clinical and neuropathologic criteria for Alzheimer disease (AD) but differs from pure AD in having a neocortical predominance of diffuse and neuritic plaques (NP), with very few neurofibrillary tangles (NFT). We investigated the immunoreactivity of NP with a monoclonal antibody against paired helical filaments (PHF) composed of phosphorylated microtubule associated protein tau. With routine thioflavin-S preparations, 12 LBV and 14 AD cases had similar numbers of NP, but the LBV had significantly (P<0.05) fewer NFT per microscopic field in the midfrontal cortex. Among subjects with midfrontal NFT, 81–84% of NP in AD and LBV were anti-PHF positive. Among subjects without midfrontal NFT, 52% of NP in AD but only 12% of NP in LBV cases were anti-PHF positive (P<0.05). LBV differs from AD in that its NP generally do not contain PHF, unless they are accompanied by neocortical NFT.     

Uptake of inorganic phosphate by the maternal border of the guinea pig placenta

Mechanism of uptake of inorganic phosphate (P_i) by the maternal border of the dually perfused guinea pig placenta was studied using the paired-tracer dilution technique with³²P-phosphate and¹⁴C-sucrose being the tracers. Placental uptake of radioactive phosphate increased when the concentration of P_i in the perfusion fluid was reduced, and it decreased during anoxia, in presence of CN or during perfusion with low-Na or Na-free fluids. Iodoacetate was without effect. These observations are consistent with placental uptake of P_i being effected by a carrier mediated process dependent on external Na and, partly, on placental metabolism. Unidirectional flux of P_i from the maternal vascular space into the cell compartment of the placenta, estimated from the values of instantaneous extraction of³²P, correlated significantly with foetal weight. The flux per unit weight of the foetus was 17.0±1.0 nmol · min^–1 g^–1.     

阿尔茨海默病脑脊液磷酸化神经丝及双螺旋丝免疫活性

目的探讨阿尔茨海默病（Ａｌｚｈｅｉｍｅｒｓｄｉｓｅａｓｅ,ＡＤ）患者脑脊液（ＣＳＦ）磷酸化神经丝（ＰＮＦ）和双螺旋丝（ＰＨＦ）免疫活性的变化及临床意义。方法采用竞争抑制型ＥＬＩＳＡ检测ＡＤ的ＣＳＦ中ＰＮＦ和ＰＨＦ的免疫活性,并与对照组即多发梗死性痴呆（ＭＩＤ）、其他神经疾病（ＯＤＣ）、精神分裂症（ＳＣＨ）及正常人（ＮＣ）进行比较。结果ＡＤ组ＣＳＦ中ＰＮＦ活性与ＭＩＤ、ＮＣ、ＳＣＨ无显著性差异。ＡＤ组ＣＳＦ中ＰＨＦ活性高于各对照组,而其ＰＮＦ／ＰＨＦ比值低于各对照组,有显著性意义。ＰＨＦ值与对照组个体间重叠的４例ＡＤ中仅１例其ＰＮＦ／ＰＨＦ值与相应的ＭＩＤ有重叠。结论单纯测定ＣＳＦ中ＰＮＦ免疫活性对ＡＤ的鉴别诊断无意义,测定ＣＳＦ中ＰＨＦ活性与ＰＮＦ／ＰＨＦ比值相结合可提高ＡＤ的诊断正确率,有可能发展为有临床意义的实验室诊断试验。     

l-Lactate andd-lactate carriers on the fetal and the maternal side of the trophoblast in the isolated guinea pig placenta

The transfer of¹⁴C-labelledd- orl-lactate (test substance) relative to³H-l-glucose (control substance, extracellular marker) into the trophoblast of the isolated guinea pig placenta was determined during an open loop perfusion on both sides. Using a single passage, paired tracer dilution technique, the maximal lactate uptake (U _max) was derived from the venous concentration ratio of lactate tol-glucose.A significant metabolism ofl-lactate was not observed. The lactate uptake, which occurred in all placentas studied, was not significantly different on the fetal and maternal side. Within one placenta thel-lactate uptake was always higher than thed-lactate uptake. The uptake of bothl- andd-lactate could be inhibited by phloretin. The lactate uptake was inversely correlated with the pH of the perfusate fluid within the range from 6.2–8. A first order saturation kinetic (Hofstee-plot) was used to approximate the relationship between thel-lactate uptake and the chemicall-lactate concentration. We conclude that similar lactate carriers exist in the membranes on both the maternal and the fetal side of the trophoblast.Supported by the Deutsche Forschungsgemeinschaft     

学习不良初中生心理健康状况的配对研究

目的　探讨学习不良初中生的心理健康状况及其与学习不良的关系。方法　采用 1∶ 1配对的对照研究方法 ,应用中学生心理健康量表 ( MSSMHS)对 1 1 0名初中生进行测查。结果　MSSMHS测查中 ,学习不良组的心理异常检出率高于对照组 ,差异有显著性意义 ( P<0 .0 5 ) ;学习不良组共有 9项指标高于对照组 ,差异有显著性意义 ( P<0 .0 5 ) ;学习不良组强迫、人际关系敏感、焦虑、学习压力及情绪不平衡因子轻度异常。结论　学习不良初中生的心理健康问题不容忽视