Alteration of synaptic plasticity in rat dorsal striatum induced by chronic ethanol intake and withdrawal via ERK pathway.

AIM: The dorsal striatum has been proposed to contribute to the formation of drug-seeking behaviors, leading to excessive and compulsive drug usage, such as addiction. The current study aimed to investigate the involvement of extracellular signal-regulated kinase (ERK) pathway in the modification of striatal synaptic plasticity. METHODS: Ethanol was administered to rats in drinking water at concentration of 6% (v/v) for 30 days. Rats were sacrificed on day 10, 20, or 30 during ethanol intake or on withdrawal day 1, 3, or 7 following 30-d ethanol intake. The striata were removed either for electrophysiological recording or for protein immuno-blot analysis. Extracellular recording technique was used to record population spikes (PS) induced by high-frequency stimulation (HFS) in the dorsolateral striatum (DLS). RESULTS: Corticostriatal long-term depression (LTD) was determined to be dependent upon ERK signaling. Chronic ethanol intake (CEI) attenuated ERK phosphorylation and LTD induction, whereas withdrawal for one day (W1D) potentiated ERK phosphorylation and LTD induction. These results showed that the impact of chronic ethanol intake and withdrawal on corticostriatal synaptic plasticity was associated with ethanol's effect on ERK phosphorylation. In particular, pharmacological inhibition of ERK hyper-phosphorylation by U0126 prevented LTD induction in the DLS and attenuated ethanol withdrawal syndrome as well. CONCLUSION: In rat DLS, chronic ethanol intake and withdrawal altered LTD induction via ERK signaling pathway. Ethanol withdrawal syndrome is mediated, at least partly, by ERK hyper-phosphorylation in the DLS.

[Non-stationary interference or intrinsic low frequency fluctuation of dynamic system--the correlation between non-stationarity and short-term analysis of heart rate variability].

The non-stationary interference with the analysis parameters of short-term heart rate variability (HRV) has been studied. The results show that although all considered parameters fluctuate with the lapse of time, only HFnorm and sample entropy (SE) correlate significantly with non-stationary interference. Therefore, the low frequency fluctuations of HRV contain not only the non-stationary interference, but also the intrinsic cardiac dynamic characteristics. Specially, the results of the base-scale entropy (BE) analysis of three groups of people, and of three kinds of noises are contrasted. It is shown that, at the expense of outstanding anti-nonstationarity, BE fails to depict the long range correlation of HRV.

DHEA-neuroprotection and -neurotoxicity after transient cerebral ischemia in rats.

Dehydroepiandrosterone (DHEA) has been implicated not only to prevent N-methyl-D-aspartate (NMDA)-induced neurotoxicity but also to enhance Ca(2+) influx through NMDA receptor (NMDAr). However, these DHEA effects, which would produce inconsistent outcomes about neuronal damages, are not well studied in ischemia-induced cerebral damages. Herein, we report that a single administration of DHEA (20 mg/kg) during 3 to 48 h after transient global cerebral ischemia in rats exerted neuroprotective effects such as reduction of ischemia-induced neuronal death in the hippocampal CA1 and improvement of ischemia-induced deficits in spatial learning. By contrast, at 1 h before or after ischemia, the administration of DHEA exacerbated the ischemia-induced neuronal death and learning impairment. This DHEA neurotoxicity appeared to be caused by DHEA itself, but not through its metabolite testosterone, and was inhibited by a pretreatment with the NMDAr blocker MK801 or the sigma-1 (sigma(1)) receptor antagonist NE100. However, the DHEA neuroprotection was blocked by NE100. These results show that DHEA not only provides robust ischemic neuroprotection with a long therapeutic opportunity but also exerts neurotoxicity when administered during ischemia and early reperfusion, which points to the importance of administration timing of DHEA in the clinical treatment of brain damages by the transient brain ischemia including stroke.

Chronic ethanol intake-induced changes in open-field behavior and calcium/calmodulin-dependent protein kinase IV expression in nucleus accumbens of rats: naloxone reversal.

AIM: To investigate the effects of chronic ethanol intake on the locomotor activity and the levels of calcium/calmodulin-dependent protein kinase IV (CaM kinase IV) in the nucleus accumbens (NAc) of rats. Simultaneously, the effects of nonselective opioid antagonist (naloxone) on the CaM kinase IV expression in the NAc and ethanol consumption of rats were also observed. METHODS: Ethanol was administered in drinking water at the concentrations of 6% (v/v), for 28 d. The locomotor activity of rats was investigated in the open-field apparatus. CaM kinase IV levels in the NAc were analyzed using Western blotting. RESULTS: Rats consuming ethanol solution exhibited a significant decrease of ambulation activity, accompanied by a reduced frequency of explorative rearing in an open-field task on d 7 and d 14 of chronic ethanol ingestion, whereas presumed adaptation to the neurological effects of ethanol was observed on d 28. Chronic ethanol intake elicited a significant decrease of the CaM kinase IV expression in the nuclei, but not in the cytoplasm of the NAc on d 28. Naloxone treatment significantly attenuated ethanol intake of rats and antagonized the decrease of CaM kinase IV in the nuclei of NAc neurons. The cytosolic CaM kinase IV protein levels of the NAc also increased in rats exposed to ethanol plus naloxone. CONCLUSION: Chronic ethanol intake-induced changes in explorative behavior is mediated at least partly by changes in CaM kinase IV signaling in the nuclei of the NAc, and naloxone attenuates ethanol consumption through antagonizing the downregulation of CaM kinase IV in the NAc.

Dehydroepiandrosterone sulfate prevents ischemia-induced impairment of long-term potentiation in rat hippocampal CA1 by up-regulating tyrosine phosphorylation of NMDA receptor.

We have reported that dehydroepiandrosterone sulfate (DHEAS) reduces the threshold for long-term potentiation (LTP) in Shaffer collateral-CA1 synapses through the amplification of Src-dependent NMDA receptor signaling. The present study is a follow-up of the above reports, aiming at evaluating the effects of DHEAS on the impaired LTP in reversible forebrain ischemic rats. Transient (20 min) incomplete forebrain ischemia led to an impaired LTP in the hippocampal CA1 region without damages to the basal synaptic transmission between the Shaffer collaterals and pyramidal neurons. Repetitive administrations of DHEAS (20 mg/kg for 3 days) from the first 3 h of reperfusion, but not acute DHEAS application (50 microM), prevent the impairment of LTP produced by ischemia. Co-administration of the specific sigma(1) receptor antagonist NE100 with DHEAS completely prevented the protective effect of DHEAS. In contrast, progesterone (PRGO) not only had no protective effect against the ischemic LTP impairment, but also attenuated the protective effect of DHEAS on the impaired LTP. Tyrosine phosphorylation of NMDA receptor subunit 2B (NR2B) significantly decreased after ischemia, whereas that of NR1 had no obvious change. Furthermore, the repetitive administration of DHEAS improved the reduction in tyrosine phosphorylation of NR2B. These findings suggest that the repetitive activation of sigma(1) receptor induced by DHEAS might prevent the ischemic LTP impairment through regulating the tyrosine phosphorylation of NR2B.

Functional organization of the primary motor cortex characterized by event-related fMRI during movement preparation and execution.

Neuronal recording and neuroimaging studies have shown that the primary motor area (M1) not only participates in motor execution, but is also engaged during movement preparation. The purpose of the present study was to map the distribution of the preparation- and execution-related activity within the contralateral M1 using functional magnetic resonance imaging. Eleven subjects performed a delayed sequential finger movement task, in which a CUE signal indicated a movement sequence in advance of an imperative GO signal. The hemodynamic response related to the CUE and GO signals decreased in a linear fashion across the central sulcus, with activity greater along the lateral extent compared to the medial extent. This decrease was especially evident in the epoch following the CUE. Our data reveal a pattern of functional organization within M1 related to the preparation and execution of movement sequences.