Mei Zhou

Huazhong University of Science and Technology, Wu-han-shih, Hubei, China

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Publications (8)26.75 Total impact

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    ABSTRACT: Chronic cerebral hypoperfusion (CCH) causes learning and memory impairments and increases the risk of Alzheimer disease (AD) and vascular dementia(VD) through several biologically plausible pathways, yet the mechanisms underlying the disease process remained unclear particularly in a temporal manner. We performed permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH. To determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are altered at different stages of cognitive impairment caused by CCH, adult male SD rats were randomly distributed into sham-operated 4, 8 and 12 weeks group, 2VO 4, 8 and 12 weeks group. Learning and memory performance were evaluated with Morris water maze (MWM) and long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Expression of NeuN, HCN1 and HCN2 in hippocampal CA1, DG and CA3 areas was quantified by immunohistochemistry and western blotting. Our data showed that CCH induced a remarkable spatial learning and memory deficits in rats of 2VO 4, 8, and 12 weeks group although neuronal loss only occurred after 4 weeks of 2VO surgery in CA1. In addition, a significant reduction of HCN1 surface expression in CA1 was observed in the group that suffered 4 weeks ischemia but neither 8 nor 12 weeks. However, HCN2 surface expression in CA1 increased throughout the ischemia time-scales (4, 8 and 12w). Our findings indicate spatial learning and memory deficits in the CCH model are associated with disturbed HCN1 and HCN2 surface expression in hippocampal CA1. The altered patterns of both HCN1 and HCN2 surface expression may be implicated in the early stage (4w) of spatial learning and memory impairments; and the stable and long-lasting impairments of spatial learning and memory may partially attribute to the up-regulated HCN2 surface expression. Copyright © 2015. Published by Elsevier Inc.
    Neurobiology of Learning and Memory 05/2015; 123. DOI:10.1016/j.nlm.2015.05.005 · 3.65 Impact Factor
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    ABSTRACT: Chronic cerebral hypoperfusion may cause cognitive impairment, but the underlying neurobiological mechanism is poorly understood. In this study, we investigated whether clonidine, an α2-adrenergic receptor agonist, could play neuroprotective role against chronic ischemic brain injury and the potential mechanism. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). Three weeks later, rats were administrated with 0.05 mg/kg clonidine (intraperitoneal injection, i.p.) for 7 days. Cognitive function was evaluated by Morris water maze (MWM). Immunofluorescence and western blots were used to detect the protein levels. Our results showed that the cognitive function was partially impaired, the expression of neuronal nuclei (NeuN), Glutamic acid decarboxylase 67 (GAD67) and γ-aminobutyric acid- B receptor 1 (GABABR1) in hippocampal CA1 area were attenuated after 2VO, which were not observed in CA3 and dentate gyrus (DG). Administration of 0.05 mg/kg clonidine (i.p.) for 7 days could improve cognitive function and the expression of NeuN, GAD67 and GABABR1 in CA1, but did not affect the protein levels in CA3 and DG. These findings demonstrated that clonidine could ameliorate cognitive deficits and neuronal impairment induced by chronic cerebral hypoperfusion via up-regulation of GABABR1 and GAD67 in hippocampal CA1.
    Pharmacology Biochemistry and Behavior 01/2015; 132. DOI:10.1016/j.pbb.2015.01.018 · 2.78 Impact Factor
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    ABSTRACT: The hyperpolarization-activated cyclic-nucleotide-gated non-selective cation (HCN) channels play a vital role in the neurological basis underlying nervous system diseases. However, the role of HCN channels in drug addiction is not fully understood. In the present study, we investigated the expression of HCN1 and HCN2 subunits in hippocampal CA1 and the potential molecular mechanisms underlying the modulation of HCN channels in rats with chronic morphine exposure with approaches of electrophysiology, water maze, and Western blotting. We found that chronic morphine exposure (5 mg/kg, sc, for 7 days) caused an inhibition of long-term potentiation (LTP) and impairment of spatial learning and memory, which is associated with a decrease in HCN1, and an increase in HCN2 on cell membrane of hippocampal CA1 area. Additional experiments showed that the imbalance of cell membrane HCN1 and HCN2 expression under chronic morphine exposure was related to an increase in expression of TPR containing Rab8b interacting protein (TRIP8b) (1a-4) and TRIP8b (1b-2), and phosphorylation of protein kinase A (PKA) and adaptor protein 2 μ2 (AP2 μ2). Our results demonstrate the novel information that drug addiction-induced impairment of learning and memory is involved in the imbalance of HCN1 and HCN2 subunits, which is mediated by activation of TRIP8b (1a-4), TRIP8b (1b-2), PKA and AP2 μ2.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 10/2014; 56. DOI:10.1016/j.pnpbp.2014.09.010 · 3.69 Impact Factor
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    ABSTRACT: Hyperpolarization-activated cyclic-nucleotide-gated cation nonselective (HCN) channels are involved in the pathology of nervous system diseases. HCN channels and γ-aminobutyric acid (GABA) receptors can mutually co-regulate the function of neurons in many brain areas. However, little is known about the co-regulation of HCN channels and GABA receptors in the chronic ischemic rats with possible features of vascular dementia. Protein kinase A (PKA) and TPR containing Rab8b interacting protein (TRIP8b) can modulate GABAB receptors cell surface stability and HCN channel trafficking, respectively, and adaptor-associated kinase 1 (AAK1) inhibits the function of the major TRIP8b-interacting protein adaptor protein 2 (AP2) via phosphorylating the AP2 μ2 subunit. Until now, the role of these regulatory factors in chronic cerebral hypoperfusion is unclear. In the present study, we evaluated whether and how HCN channels and GABAB receptors were pathologically altered and investigated neuroprotective effects of GABAB receptors activation and cross-talk networks between GABAB receptors and HCN channels in the hippocampal CA1 area in chronic cerebral hypoperfusion rat model. We found that cerebral hypoperfusion for 5 weeks by permanent occlusion of bilateral common carotid arteries (two-vessel occlusion, 2VO) induced marked spatial and nonspatial learning and memory deficits, significant neuronal loss and decrease in dendritic spine density, impairment of long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses, and reduction of surface expression of GABAB R1, GABAB R2, and HCN1, but increase in HCN2 surface expression. Meanwhile, the protein expression of TRIP8b (1a-4), TRIP8b (1b-2), and AAK1 was significantly decreased. Baclofen, a GABAB receptor agonist, markedly improved the memory impairment and alleviated neuronal damage. Besides, baclofen attenuated the decrease of surface expression of GABAB R1, GABAB R2, and HCN1, but downregulated HCN2 surface expression. Furthermore, baclofen could restore expression of AAK1 protein and significantly increase p-PKA, TRIP8b (1a-4), TRIP8b (1b-2), and p-AP2 μ2 expression. Those findings suggested that, under chronic cerebral hypoperfusion, activation of PKA could attenuate baclofen-induced decrease in surface expression of GABAB R1 and GABAB R2, and activation of GABAB receptors not only increased the expression of TRIP8b (1a-4) and TRIP8b (1b-2) but also regulated the function of TRIP8b via AAK1 and p-AP2 μ2, which restored the balance of HCN1/HCN2 surface expression in rat hippocampal CA1 area, and thus ameliorated cognitive impairment.
    Molecular Neurobiology 05/2014; 50(2). DOI:10.1007/s12035-014-8736-3 · 5.14 Impact Factor
  • Chang-Jun Li · Yun Lu · Mei Zhou · Lian-Jun Guo
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    ABSTRACT: The recording of hippocampal and cortical long-term potentiation (LTP) in rats in vivo is an appropriate and commonly used method to describe changes in cellular mechanisms underlying synaptic plasticity. Recently, we introduced a method for the simultaneous recording of LTP in bilateral CA1 regions and parietal association cortex (PtA), and observed differences between the Schaffer collateral-CA1 pathway (SC), Schaffer collateral/associational commissural pathway (SAC) and Schaffer collateral/associational commissural-cortex pathway (SACC). In this study, we found that (1) synaptic transmission of the SAC and SACC pathways depended on hippocampal commissural fibers [dorsal and ventral hippocampal commissural fibers, the medial septum (MS) and hippocampal CA3 commissural fibers], (2) nerve conduction velocity of the SACC pathway might be higher than that of the SAC pathway, (3) the input/output (I/O) curve of the SC pathway was shifted to the left side, compared to that of the SAC and SACC pathways, (4) all three pathways could induce stable LTP; however, LTP of the SAC and SACC pathways was much stronger than that of the SC pathway, (5) the degree of paired-pulse facilitation (PPF) was weaker in the SC pathway than that in the SAC and SACC pathways, (6) after cutting off the corpus callosum and commissural fibers, spatial learning and memory were impaired, and the ability to explore the novel environment and spontaneous locomotor activity were weakened. Taken together, our results suggested that hippocampal commissural fibers were very important for exchanging information between hemispheres, and basic differences in electrophysiological properties of hippocampal-cortical neural networks play a vital role in the processes of learning and memory.
    Journal of Neural Transmission 02/2014; 121(6). DOI:10.1007/s00702-014-1164-8 · 2.40 Impact Factor
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    ABSTRACT: Activation of alpha2-adrenoceptors inhibits long-term potentiation and long-term depression in many brain regions. However, effectiveness and mechanism of alpha2-adrenoceptors for synaptic plasticity at the Schaffer collateral-CA1 synapses in rat in vivo is unclear. In the present study, we investigated the effects of alpha2-adrenoceptors agonist clonidine on high-frequency stimulation (HFS)-induced long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the Schaffer collateral-CA1 synapse of rat hippocampus in vivo. Clonidine (0.05, 0.1 mg/kg, ip) inhibited synaptic plasticity in a dose-dependent manner, accompanying with the decreasing of aortic pressure and heart rate (HR) in anesthetized rats. Clonidine (1.25, 2.5 μg/kg, icv, 10 min before HFS) also dose-dependently inhibited synaptic plasticity, which had no remarkable effect on HR and aortic pressure. But, 20 min after HFS, administration of clonidine (2.5 μg/kg) had no effect on LTP. The inhibitory effect of clonidine (2.5 μg/kg) on LTP was completely reversed by yohimbine (18 μg/kg, icv) and ZD7288 (5 μg/kg, icv). Moreover, the inhibition was accompanied by a significant increase of the normalized PPF ratio. Furthermore, clonidine at 1 and 10 μM significantly decreased glutamate (Glu) content in the culture supernatants of hippocampal neurons, and yohimbine at 1 and 10 μM had no effect on Glu release, while it could reverse the inhibition of clonidine (1 and 10 μM) on Glu release. In conclusion, clonidine can suppress the induction of LTP at the Schaffer collateral-CA1 synapse, and the possible mechanism is that activation of presynaptic alpha2-adrenoceptors reduces the Glu release by inhibiting HCN channels.
    Cellular and Molecular Neurobiology 08/2013; 33(8). DOI:10.1007/s10571-013-9974-z · 2.51 Impact Factor
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    ABSTRACT: Menispermum dauricum rhizome has been widely used in China to treat various cardiovascular and thrombosis disorders. Some studies have reported that the phenolic alkaloids of Menispermum dauricum rhizome (PAM) have protective effects against brain ischemia injury, but the mechanism of this action remains to be clarified. In the present study, we investigated the possible mechanisms of action of PAM on experimental brain ischemia injury. Oxygen and glucose deprivation (OGD) in rat primary cortical cultures and middle cerebral artery occlusion in rats were used to mimic ischemia-reperfusion injury, respectively. The results suggested that PAM protected rat primary cortical cultures against OGD-reoxygenation induced cytotoxicity. PAM decreased extracellular glutamate content and markedly prevented the effects induced by OGD on protein level of GLT-1 and EAAC1 glutamate transporters. In addition, it reduced intracellular ROS generation. In vivo, PAM significantly reduced cerebral infarct area and ameliorated neurological functional deficits at different time points. Our findings revealed that the possible mechanism of action of PAM protected against brain ischemia injury involves regulation of GLT-1, EAAC1 and ROS generation.
    Molecules 12/2012; 17(3):2725-37. DOI:10.3390/molecules17032725 · 2.42 Impact Factor
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    ABSTRACT: Opuntia is a traditional plant from China with medicinal applications. In this experiment, polysaccharides from Opuntia Milpa Alta (MAPs) were analyzed using gas chromatograph-mass spectrometer (GC-MS) method and result showed that MAPs contained mannose (6.37%), rhamnose (14.94%), xylose (1.99%), arabinose (24.07%), galactose (38.25%), ribose (2.63%) and glucose (11.48%). The neuroprotective effects of MAPs were evaluated at the mechanistic level in vitro models of cerebral ischemic injury. In vitro oxygen/glucose deprivation (OGD) model, MAPs (0.5 μg/ml, 5 μg/ml, 50 μg/ml) effectively increased cell viability by methyl thiazolyl tetrazolium (MTT) assay, inhibited cell cytotoxicity by lactate dehydrogenase (LDH) assay, reduced neuronal cell death, suppressed the production of intracellular reactive oxygen species (ROS), decreased of intracellular free Ca(2+) concentrations ([Ca(2+)](i)), and reduced extracellular glutamate level. Therefore, MAPs might prevent intracellular calcium overload and decreased glutamate excitotoxicity, both of which can cause neuronal injury and death in vitro models of cerebral ischemic injury.
    International journal of biological macromolecules 07/2011; 49(4):681-7. DOI:10.1016/j.ijbiomac.2011.06.031 · 2.86 Impact Factor