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Objective: To investigate the effects of IMPX977 on long term potentiation (LTP) at Schaffer collateral-CA1 synapses in vitro and on methyl CpG binding protein 2 (Mecp2) expression in mice cortex and hippocampus. Methods: Thirty-two C57BL/6 mice were randomly divided into four groups: control, olive oil (vehicle), IMPX977 low (5 mg/kg) and high (15 mg/kg) groups. Mice were administrated every other day orally for two weeks. Extracellular recording technique in vitro was used to record the effects of IMPX977 on Schaffer collateral-CA1 LTP pathway in acute mice hippocampal slices. The Mecp2 protein expression level was detected by Western blotting. Results: Compared to the control group, vehicle did not alter the synaptic transmission in Schaffer collateral-CA1 synapses, however, IMPX977 at concentrations of 5 mg/kg and 15 mg/kg significantly enhanced fEPSP (field excitatory postsynaptic potential) slope in Schaffer collateral-CA1 pathway to (179.6 ± 17.8)% and (191.4 ± 21.4)%, individually 60 min after HFS, IMPX977 improved LTP induction significantly at Schaffer collateral-CA1 pathway at least. Also, IMPX977 significantly elevated MeCP2 protein level in cortex. Conclusion: The effects of IMPX977 on synaptic transmission and Mecp2 protein expression provided convincing evidence that IMPX977 could be promising new drug candidates for Rett syndrome treatment.
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Transcranial magnetic stimulation (TMS) is a non-invasive, non-pharmacological technique that is able to modulate cortical activity beyond the stimulation period. The residual aftereffects are akin to the plasticity mechanism of the brain and suggest the potential use of TMS for therapy. For years, TMS has been shown to transiently improve symptoms of neuropsychiatric disorders, but the underlying neural correlates remain elusive. Recently, there is evidence that altered connectivity of brain network dynamics is the mechanism underlying symptoms of various neuropsychiatric illnesses. By combining TMS and electroencephalography (EEG), the functional connectivity patterns among brain regions, and the causal link between function or behaviour and a specific brain region can be determined. Nonetheless, the brain network connectivity are highly complex and involve the dynamics interplay among multitude of brain regions. In this review article, we present previous TMS-EEG co-registration studies, which explore the functional connectivity patterns of human cerebral cortex. We argue the possibilities of neural correlates of long-term potentiation/ depression (LTP-/LTD)-like mechanisms of synaptic plasticity that drive the TMS aftereffects as shown by the dissociation between EEG and motor evoked potentials (MEP) cortical output. Here, we also explore alternative explanations that drive the EEG oscillatory modulations post TMS. The precise knowledge of the neurophysiological mechanisms underlying TMS will help characterise disturbances in oscillatory patterns, and the altered functional connectivity in neuropsychiatric illnesses.
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Many intracellular proteins and signaling cascades contribute to the sensitivity of N-methyl-D-aspartate receptors (NMDARs). One such putative contributor is the serine/threonine kinase, protein kinase C (PKC). Activation of PKC by phorbol 12-myristate 13-acetate (PMA) causes activation of extracellular signal-regulated kinase (ERK) and promotes the formation of new spines in cultured hippocampal neurons. The purpose of this study was to examine which PKC isoforms are responsible for the PMA-induced augmentation of long-term potentiation (LTP) in the CA1 stratum radiatum of the hippocampus in vitro and verify that this facilitation requires NMDAR activation. We found that PMA enhanced the induction of LTP by a single episode of theta-burst stimulation in a concentration-dependent manner without affecting to magnitude of baseline field excitatory postsynaptic potentials. Facilitation of LTP by PMA (200 nM) was blocked by the nonspecific PKC inhibitor, Ro 31-8220 (10microM); the selective PKCdelta inhibitor, rottlerin (1microM); and the PKCepsilon inhibitor, TAT-epsilonV1-2 peptide (500 nM). Moreover, the NMDAR blocker DL-APV (50microM) prevented enhancement of LTP by PMA. Our results suggest that PMA contributes to synaptic plasticity in the nervous system via activation of PKCdelta and/or PKCepsilon, and confirm that NMDAR activity is required for this effect.
Subject(s)
2-Amino-5-phosphonovalerate , Acetophenones , Benzopyrans , Excitatory Postsynaptic Potentials , Hippocampus , Indoles , Long-Term Potentiation , Nervous System , Neurons , Phorbols , Phosphotransferases , Protein Isoforms , Protein Kinases , Proteins , Receptors, N-Methyl-D-Aspartate , SpineABSTRACT
Objective To observe the effect of electroacupuncture(EA) on the learning-memory ability in Alzheimer's disease(AD) rats.Methods Thirty SD rats were equally randomized into control,model and EA groups.AD model was established by injecting ?-amyloid(A?25-35,10?g) into the bilateral dentate gyri of the hippocampal CA 1 area(AP-3.5mm,ML?2.0mm,DV 2.7mm).EA(4Hz,1-2mA) was applied to "Baihui"(GV 20),"Dazhui"(GV 14),bilateral "Shenshu"(BL 23) and bilateral "Yongquan"(KI 1) for 30min,once daily for 7 days.The learning-memory ability was detected by using step-down test.Long term potentiation(LTP) of hippocampal CA 1 area was recorded by using tungsten microelectrodes after high frequency stimulation(HFS) conditioning of the cortical anterior perforated substance.Results In AD rats,the error number and total error time of step-down test were increased significantly(P
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Objective To evaluate the role of Src kinase in the induction and maintenance of spinal long-term potentiation(LTP).Methods The C-fiber evoked field potentials were recorded at the superficial layers of spinal dorsal horn at the lumbar enlargement.Results ① Genistein(200?mol/L) or PP2(100?mol/L),a selective Src kinase inhibitor,completely blocked LTP induction when administered at 30min prior to tetanic stimulation.② Genistein or PP2 reversed spinal LTP in a time-dependent manner.At 15min after LTP induction,Genistein(200?mol/L) or PP2(100?mol/L) reversed LTP completely.At 30min after LTP induction,however,the same concentration of Genistein or PP2 did not affect the spinal LTP.Conclusion Activation of Src kinase in spinal dorsal horn may be crucial for the induction and early-phase maintenance of LTP of C-fiber evoked field potentials.
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AIM: To study the effects of huperzine A on the theta-rhythm and long-term potentiation in CA1 pyramidal neurons in adult rat hippocampal slices and to get insight into the cell electrophysiological mechanisms underlying the potentiation of learning and memory by Huperzine A. METHODS: The intracellular recordings from CA1 pyramidal neurons in hippocampal slices related to learning and memory were made to analyze the mechanisms of Hup-A action. RESULTS: Power of frequencies ranged from 4 to 10 Hz was not significantly difference between pre-membrane potential oscillations (MPOs) and post-MPOs in control group, but it was significantly (P
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Objective To investigate the effect of active fraction A (TXR-A) extracted from Tiaoxin Recipe (TXR) on inhibition of corticosterone on long-term potentiation (LTP) induced by high frequency stimulation (HFS) in rat hippocampal slices. Methods The slices were divided into control, corticosterone, corticosterone+TXR, and corticosterone+different concentration of TXR-A groups, then were incubated with artificial cerebrospinal fluid (ACSF) added by drugs for 1 h before recording and were perfused with the same ACSF during recording. Population spike (PS) was recorded from stratum pyramidale of area CA1 using extracellular recording following stimulation of Schaffer collaterals in rat hippocampal slices. Then a 100 Hz, 100 pulses HFS was used to induce LTP. Results PS amplitude was decreased significantly vs that in the control group, when the slices were pre-incubated in ACSF added by corticosterone (2 ?mol/L) over 1.5 h, meaning that LTP was inhibited by corticosterone. However, PS amplitude of the slices pre-incubated in ACSF added by corticosterone (2 ?mol/L) and high concentration TXR-A was increased significantly vs that of corticosterone pre-treating slices, meaning that high concentration TXR-A enhanced LTP inhibited by corticosterone. Furthermore, increased LTP amplitude in high concentration TXR-A was much more than that in TXR. Conclusion TXR-A is one of main TXR active ingredients which facilitate LTP inhibited by corticosterone in area CA1 of rat hippocampal slices. The antagonist (effect) on corticosterone inhibition on LTP is one of the mechanisms to benefit the intelligence.
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Objective To investigate the changes of expression of N-methyl-D-aspartate receptor(NMDAR)and mitogen activated protein kinase(MAPK)in Alzheimer disease(AD)rat model. Methods AD rat model was established by injection of amyloid-beta protein 1-40 1?l(10 g/L)into hippocampus of rat.NMDAR-mRNA and MAPK protein were immunostained by in situ hybradization histochemistry and immunohistochemistry respectively.Learning and memory ability,LTP were determined by Morris water maze and electrophysiological methods respectively. Results The escape latent was prolongated in Alzheimer rats two weeks after injection of A? than in control rats and in rats before the injection of A?(P