Gavin S Dawe

National University Health System, Singapore

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Publications (48)179 Total impact

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    Brain Research 06/2014; · 2.88 Impact Factor
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    ABSTRACT: Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination.
    Cell adhesion & migration 04/2014; 8(4). · 2.34 Impact Factor
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    ABSTRACT: A novel signal folding and reconstruction scheme for neural recording applications that exploits the $1/f^{n}$ characteristics of neural signals is described in this paper. The amplified output is ‘folded’ into a predefined range of voltages by using comparison and reset circuits along with the core amplifier. After this output signal is digitized and transmitted, a reconstruction algorithm can be applied in the digital domain to recover the amplified signal from the folded waveform. This scheme enables the use of an analog-to-digital convertor with less number of bits for the same effective dynamic range. It also reduces the transmission data rate of the recording chip. Both of these features allow power and area savings at the system level. Other advantages of the proposed topology are increased reliability due to the removal of pseudo-resistors, lower harmonic distortion and low-voltage operation. An analysis of the reconstruction error introduced by this scheme is presented along with a behavioral model to provide a quick estimate of the post reconstruction dynamic range. Measurement results from two different core amplifier designs in 65 nm and 180 nm CMOS processes are presented to prove the generality of the proposed scheme in the neural recording applications. Operating from a 1 V power supply, the amplifier in 180 nm CMOS has a gain of 54.2 dB, bandwidth of 5.7 kHz, input referred noise of 3.8 $mu V_{rms}$ and power dissipation of 2.52 $mu {rm W}$ leading to a NEF of 3.1 in spike band. It exhibits a dynamic range of 66 dB and maximum SNDR of 43 dB in LFP band. It also reduces system level power (by reducing the number of bits in the ADC by 2) as well as data rate to 80% of a conventional design. In vivo measurements validate the ability of t- is amplifier to simultaneously record spike and LFP signals.
    IEEE Transactions on Biomedical Circuits and Systems 01/2014; 8(4):528-542. · 2.74 Impact Factor
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    ABSTRACT: Calcium independent phospholipase A2 (iPLA2) is an 85kDa protein that catalyzes the hydrolysis of the sn-2 acyl ester bond to liberate free fatty acids and lysophospholipids. In this study, we determined the role of constitutive iPLA2β in long term potentiation (LTP) of the hippocampal prefrontal cortex pathway in vivo. We also examined the effect of iPLA2 knockdown using the rewarded alternation in T-maze task, a test of spatial working memory which is dependent on this pathway. Intracortical injection of an inhibitor to iPLA2, bromoenol lactone (BEL) or antisense oligonucleotide to iPLA2β in the prefrontal cortex abolished induction of hippocampal prefrontal cortex LTP. Moreover, iPLA2 inhibition and antisense knockdown resulted in increased errors in the rewarded alternation in T maze task, indicating negative effects on spatial working memory. BEL or antisense injection did not produce DNA fragmentation in the cortex as demonstrated by TUNEL assay. Results confirm a role of constitutive iPLA2β in hippocampal prefrontal cortex synaptic plasticity in vivo, and add to previous observations of a role of iPLA2 in hippocampal LTP in vitro, and long-term memory retrieval. They may be relevant in Alzheimer’s disease, and other neurodegenerative conditions that are associated with changes in iPLA2.
    Neurochemistry International 01/2014; · 2.66 Impact Factor
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    ABSTRACT: Neural prosthetics and personal healthcare have increasing need of high channel density low noise low power neural sensor interfaces. The input referred noise and quantization resolution are two essential factors which prevent conventional neural sensor interfaces from simultaneously achieving a good noise efficiency factor and low power consumption. In this paper, a neural recording architecture with dynamic range folding and current reuse techniques is proposed and dedicated to solving the noise and dynamic range trade-off under low voltage low power operation. Measured results from the silicon prototype show that the proposed design achieves 3.2 μVrms input referred noise and 8.27 effective number of bits at only 0.45 V supply and 0.94 μW/channel power consumption.
    IEEE Transactions on Biomedical Circuits and Systems 12/2013; 7(6):735-46. · 2.74 Impact Factor
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    ABSTRACT: The nucleus incertus (NI), a brainstem nucleus found in the pontine periventricular grey, is the primary source of the neuropeptide relaxin-3 in the mammalian brain. The NI neurons have also been previously reported to express several receptors and neurotransmitters, including corticotropin releasing hormone receptor 1 (CRF1) and gamma-aminobutyric acid (GABA). The NI projects widely to putative neural correlates of stress, anxiety, depression, feeding behaviour, arousal and cognition leading to speculation that it might be involved in several neuropsychiatric conditions. On the premise that relaxin-3 expressing neurons in the NI predominantly co-express CRF1 receptors, a novel method for selective ablation of the rat brain NI neurons using corticotropin releasing factor (CRF)-saporin conjugate is described. In addition to a behavioural deficit in the fear conditioning paradigm, reverse transcriptase polymerase chain reaction (RT-PCR), western blotting (WB) and immunofluorescence labelling (IF) techniques were used to confirm the NI lesion. We observed a selective and significant loss of CRF1 expressing cells, together with a consistent decrease in relaxin-3 and GAD65 expression. The significant ablation of relaxin-3 positive neurons of the NI achieved by this immunolesioning approach is a promising model to explore the neuropsychopharmacological implications of NI/relaxin-3 in behavioural neuroscience.
    Brain research 11/2013; · 2.46 Impact Factor
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    ABSTRACT: The medial prefrontal cortex (mPFC) in the rat has been implicated in a variety of cognitive processes, including working memory and expression of fear memory. We investigated the inputs from a brain stem nucleus, the nucleus incertus (NI), to the prelimbic area of the mPFC. This nucleus strongly expresses corticotropin-releasing factor type 1 (CRF1 ) receptors and responds to stress. A retrograde tracer was used to verify connections from the NI to the mPFC. Retrogradely labelled cells in the NI expressed CRF receptors. Electrophysiological manipulation of the NI revealed that stimulation of the NI inhibited spontaneous neuronal firing in the mPFC. Similarly, CRF infusion into the NI, in order to mimic a stressful condition, inhibited neuronal firing and burst firing in the mPFC. The effect of concurrent high-frequency stimulation of the NI on plasticity in the hippocampo-prelimbic medial prefrontal cortical (HP-mPFC) pathway was studied. It was found that electrical stimulation of the NI impaired long-term potentiation in the HP-mPFC pathway. Furthermore, CRF infusion into the NI produced similar results. These findings might account for some of the extra-pituitary functions of CRF and indicate that the NI may play a role in stress-driven modulation of working memory and possibly other cognitive processes subserved by the mPFC.
    European Journal of Neuroscience 05/2013; · 3.75 Impact Factor
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    ABSTRACT: A priming-challenge schedule of nicotine treatment causes long-lasting potentiation (LLP), a form of synaptic plasticity closely associated with the norepinephrine (NE) neurotransmitter system, at the medial perforant path (MPP)-dentate gyrus (DG) synapse in the rat hippocampus. Previous reports revealed that nicotine activates the locus coeruleus (LC) noradrenergic (NAergic) system and this mechanism may underlie its beta-adrenoceptor sensitive LLP effects. Clozapine, an atypical antipsychotic, is also known to activate the LC. Interactions between nicotine and clozapine are of interest because of the prevalence of smoking in patients with schizophrenia and increasing interest in the use of nicotinic receptor ligands as cognitive enhancers. Rats were subchronically primed with nicotine, clozapine or saline. Twenty one to twenty eight days later, the effects of the nicotine, clozapine or saline challenge on the evoked field excitatory postsynaptic potentials (fEPSP) at the MPP-DG monosynaptic pathway were recorded as a measure of LLP. We confirmed the hypothesis that a challenge dose of either nicotine or clozapine induces LLP exclusively in nicotine- and clozapine-primed rats, and not in saline-primed rats, thus indicating a cross-priming effect. Moreover, unilateral suppression of LC using lidocaine abolished the LLP induced by nicotine in clozapine-primed rats. Furthermore, systemic treatment with clonidine (an α2 adrenoceptor agonist that reduces NAergic activity via autoreceptors) prior to the challenge doses blocked the nicotine/clozapine-induced LLP in nicotine- and clozapine- primed rats. These findings may add to understanding of the cognitive enhancing effects of nicotine. © 2013 Wiley Periodicals, Inc.
    Hippocampus 03/2013; · 5.49 Impact Factor
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    ABSTRACT: Progress is being made in identifying possible pathogenic factors and novel genes in the development of Alzheimer's disease (AD). Many of these could contribute to 'slow excitotoxicity', defined as neuronal loss due to hyperexcitation as a consequence of decreased energy production due, for instance, to changes in insulin receptor signaling; or receptor abnormalities, such as tau-induced alterations in the N-methyl-D-aspartate (NMDA) receptor phosphorylation. As a result, glutamate becomes neurotoxic at concentrations that normally show no toxicity. In AD, NMDA receptors are overexcited by glutamate in a tonic, rather than a phasic manner. Moreover, in prodromal AD subjects, functional MRI reveals an increase in neural network activities relative to baseline, rather than a loss of activity. This may be an attempt to compensate for reduced number of neurons, or reflect ongoing slow excitotoxicity. This article reviews possible links between AD pathogenic factors such as AβPP/Aβ and tau; novel risk genes including clusterin, phosphatidylinositol-binding clathrin assembly protein, complement receptor 1, bridging integrator 1, ATP-binding cassette transporter 7, membrane-spanning 4-domains subfamily A, CD2-associated protein, sialic acid-binding immunoglobulin-like lectin, and ephrin receptor A1; metabolic changes including insulin resistance and hypercholesterolemia; lipid changes including alterations in brain phospholipids, cholesterol, and ceramides; glial changes affecting microglia and astrocytes; alterations in brain iron metallome and oxidative stress; and slow excitotoxicity. Better understanding of the possible molecular links between pathogenic factors and slow excitotoxicity could inform our understanding of the disease, and pave the way toward new therapeutic strategies for AD.
    Journal of Alzheimer's disease: JAD 03/2013; · 4.17 Impact Factor
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    ABSTRACT: A number of atypical antipsychotic drugs are known to perturb appetite regulation causing greater hyperphagia in humans and rodents than earlier generation typical agents. However, the neuronal structures that underlie hyperphagic effects are poorly understood. Arcuate nucleus (ArcN), paraventricular hypothalamic nucleus (PVN), paraventricular thalamic nucleus (PVA) and nucleus incertus (NI) have been implicated in appetite regulation. The NI is the principal source of the RLN3 peptide, which is reported to have orexigenic effects. Moreover, ArcN, PVN, and PVA receive relaxin-3 (RLN3) immunoreactive fibers from the NI and express relaxin family peptide type 3 (RXFP3) receptor. The present study was designed to evaluate the acute effects of clozapine (atypical), chlorpromazine (typical) and fluphenazine (typical) on c-Fos expression (a marker of neuronal response) in these appetite-related centers of the rat brain. The numbers of c-Fos expressing neurons in these structures were counted in immunofluorescence stained brain sections. Acute treatment with clozapine, chlorpromazine and fluphenazine differentially influenced c-Fos expression in these brain structures. This study is also the first demonstration that antipsychotics influence the NI. The patterns of the effects of these antipsychotics are related to their reported hyperphagic properties.
    Brain research 03/2013; · 2.46 Impact Factor
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    ABSTRACT: The aberrant hyperactivation of Cyclin-dependent kinase 5 (Cdk5), by the production of its truncated activator p25, results in the formation of hyperphosphorylated tau, neuroinflammation, amyloid deposition, and neuronal death in vitro and in vivo. Mechanistically, this occurs as a result of a neurotoxic insult that invokes the intracellular elevation of calcium to activate calpain, which cleaves the Cdk5 activator p35 into p25. It has been shown previously that the p25 transgenic mouse as a model to investigate the mechanistic implications of p25 production in the brain, which recapitulates deregulated Cdk5-mediated neuropathological changes, such as hyperphosphorylated tau and neuronal death. To date, strategies to inhibit Cdk5 activity have not been successful in targeting selectively aberrant activity without affecting normal Cdk5 activity. Here we show that the selective inhibition of p25/Cdk5 hyperactivation in vivo, through overexpression of the Cdk5 inhibitory peptide (CIP), rescues against the neurodegenerative pathologies caused by p25/Cdk5 hyperactivation without affecting normal neurodevelopment afforded by normal p35/Cdk5 activity. Tau and amyloid pathologies as well as neuroinflammation are significantly reduced in the CIP-p25 tetra transgenic mice, whereas brain atrophy and subsequent cognitive decline are reversed in these mice. The findings reported here represent an important breakthrough in elucidating approaches to selectively inhibit the p25/Cdk5 hyperactivation as a potential therapeutic target to reduce neurodegeneration.
    Journal of Neuroscience 01/2013; 33(1):334-343. · 6.91 Impact Factor
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    ABSTRACT: Parkinson's disease (PD), characterized by loss of dopaminergic neurons in the substantia nigra, is a neurodegenerative disorder of central nervous system. The present study was designed to investigate the therapeutic effect of ACS84, a hydrogen sulfide-releasing-L-Dopa derivative compound, in a 6-hydroxydopamine (6-OHDA)-induced PD model. ACS84 protected the SH-SY5Y cells against 6-OHDA-induced cell injury and oxidative stress. The protective effect resulted from stimulation of Nrf-2 nuclear translocation and promotion of anti-oxidant enzymes expression. In the 6-OHDA-induced PD rat model, intragastric administration of ACS84 relieved the movement dysfunction of the model animals. Immunofluorescence staining and High-performance liquid chromatography analysis showed that ACS84 alleviated the loss of tyrosine-hydroxylase positive neurons in the substantia nigra and the declined dopamine concentration in the injured striatums of the 6-OHDA-induced PD model. Moreover, ACS84 reversed the elevated malondialdehyde level and the decreased glutathione level in vivo. In conclusion, ACS84 may prevent neurodegeneration via the anti-oxidative mechanism and has potential therapeutic values for Parkinson's disease.
    PLoS ONE 01/2013; 8(4):e60200. · 3.53 Impact Factor
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    ABSTRACT: This paper presents a fully implantable 100-channel neural interface IC for neural activity monitoring. It contains 100-channel analog recording front-ends, 10 multiplexing successive approximation register ADCs, digital control modules and power management circuits. A dual sample-and-hold architecture is proposed, which extends the sampling time of the ADC and reduces the average power per channel by more than 50% compared to the conventional multiplexing neural recording system. A neural amplifier (NA) with current-reuse technique and weak inversion operation is demonstrated, consuming 800 nA under 1-V supply while achieving an input-referred noise of 4.0 μVrms in a 8-kHz bandwidth and a NEF of 1.9 for the whole analog recording chain. The measured frequency response of the analog front-end has a high-pass cutoff frequency from sub-1 Hz to 248 Hz and a low-pass cutoff frequency from 432 Hz to 5.1 kHz, which can be configured to record neural spikes and local field potentials simultaneously or separately. The whole system was fabricated in a 0.18-μm standard CMOS process and operates under 1 V for analog blocks and ADC, and 1.8 V for digital modules. The number of active recording channels is programmable and the digital output data rate changes accordingly, leading to high system power efficiency. The overall 100-channel interface IC consumes 1.16-mW total power, making it the optimum solution for multi-channel neural recording systems.
    Circuits and Systems I: Regular Papers, IEEE Transactions on 01/2013; 60(10):2584-2596. · 2.24 Impact Factor
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    ABSTRACT: For real-time monitoring of brain activities, a highdata-rate, low-power, and highly mobile neural recording system is desirable. This paper presents a complete chipset for a 100-channel wireless neural recording system, which consists of 3 ICs - a neural interface (NI) IC and a wireless power RX and data TX IC for an implant unit (IU), and a wireless data RX IC for an external head unit (EHU). With a dual S/H NI architecture and a burst-mode (BM) wideband (WB) FSK TX, the IU achieves a 100-channel recording and wireless transmission at 54.24Mb/s while consuming only 6.6mW. Using power coupling with optimal resonant load transformation and high-efficiency rectifier and LDO circuits, the whole wireless power link achieves 40% efficiency over 1cm distance with 0.5cm tissue in between. The EHU needs to transmit the RF power lower than 30mW to operate the IU. The EHU is implemented using a crystal-less BM WB FSK RX consuming only 14.4mW at 27.12Mb/s.
    Solid State Circuits Conference (A-SSCC), 2012 IEEE Asian; 01/2012
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    ABSTRACT: Advances in neuroscience research and clinical applications have increasingly called for the low-power low-noise simultaneous recording of neural signals from a large number of electrodes. The neural interface IC is one of the essential blocks to capture the weak neural signals. Presented is an energy-efficient low-noise neural recording amplifier with enhanced noise efficiency factor (NEF) for neural recording systems. Based on the conventional capacitive feedback and pseudo-resistor structure, the fully differential neural amplifier employs the current-reuse technique to achieve low noise and high current efficiency, consuming 800 nA at 1 V power supply. The measured thermal noise floor is 43nV/ √Hz and the input-referred noise is 5.71 Vrms when integrated from 1 Hz to 50 kHz, leading to an NEF of 2.59. The entire neural amplifier has been fabricated using a 0.18 m CMOS technology, occupying an area of 0.05 mm2.
    Electronics Letters 01/2012; 48(9):479-480. · 1.04 Impact Factor
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    ABSTRACT: The prolongation of QT intervals in both mothers and fetuses during the later period of pregnancy implies that higher levels of progesterone may regulate the function of the human ether-a-go-go-related gene (HERG) potassium channel, a key ion channel responsible for controlling the length of QT intervals. Here, we studied the effect of progesterone on the expression, trafficking, and function of HERG channels and the underlying mechanism. Treatment with progesterone for 24 h decreased the abundance of the fully glycosylated form of the HERG channel in rat neonatal cardiac myocytes and HERG-HEK293 cells, a cell line stably expressing HERG channels. Progesterone also concentration-dependently decreased HERG current density, but had no effect on voltage-gated L-type Ca(2+) and K(+) channels. Immunofluorescence microscopy and Western blot analysis show that progesterone preferentially decreased HERG channel protein abundance in the plasma membrane, induced protein accumulation in the dilated endoplasmic reticulum (ER), and increased the protein expression of C/EBP homologous protein, a hallmark of ER stress. Application of 2-hydroxypropyl-β-cyclodextrin (a sterol-binding agent) or overexpression of Rab9 rescued the progesterone-induced HERG trafficking defect and ER stress. Disruption of intracellular cholesterol homeostasis with simvastatin, imipramine, or exogenous application of cholesterol mimicked the effect of progesterone on HERG channel trafficking. Progesterone may impair HERG channel folding in the ER and/or block its trafficking to the Golgi complex by disrupting intracellular cholesterol homeostasis. Our findings may reveal a novel molecular mechanism to explain the QT prolongation and high risk of developing arrhythmias during late pregnancy.
    Journal of Biological Chemistry 06/2011; 286(25):22186-94. · 4.65 Impact Factor
  • Wan-Jie Chia, Gavin S Dawe, Wei-Yi Ong
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    ABSTRACT: Lipocalin 2 (LCN2) is produced by mammalian hosts to bind bacterial siderophore and sequester free iron as part of an innate immune response, and could also play a role in tissue iron homeostasis, but thus far, little is known about its expression in the CNS. The present study was carried out to study the expression of the lipocalin in the normal rat brain and after neuronal injury induced by kainate (KA). Low levels of LCN2 mRNA and protein expression were detected in most regions of the normal brain except the olfactory bulb, brainstem and cerebellum. KA lesions resulted in damage to the hippocampus, leading to an early increase at three days and a sustained elevation in LCN2 mRNA level of 16-fold, and protein expression at 80-fold in the lesioned tissue compared to controls at 2 weeks post-KA injection. The sustained elevation in mRNA expression was not detected among other lipocalins surveyed using real-time RT-PCR - apoD, PGDS, Rbp4 and LCN5. Single and double immunostaining confirmed that LCN2 is present in astrocytes in the olfactory bulb, brainstem and cerebellum of the normal brain, and reactive astrocytes in the KA-lesioned hippocampus. In conclusion, the present study showed LCN2 to be present in select brain regions, and is upregulated in astrocytes after neuronal injury induced by kainate. We postulate that, as in the periphery, LCN2 may have a role in iron transport or trafficking in the CNS.
    Neurochemistry International 06/2011; 59(5):591-9. · 2.66 Impact Factor
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    ABSTRACT: Bidirectional cell trafficking between fetus and mother during pregnancy is a well-established phenomenon observed in placental vertebrates including humans. Although studies have shown that transmigratory fetal cells, also termed pregnancy-associated progenitor cells (PAPCs), can integrate into multiple maternal organs, the integration, long-term survival, and differentiation of PAPCs in the brain has not been extensively studied. Using a murine model of fetomaternal microchimerism, we show that PAPCs integrated and persisted in several areas of the maternal brain for up to 7 months postpartum. Besides expressing neural stem cell or immature neuronal markers, PAPCs were observed to express mature neuronal markers, indicating that PAPCs adopted a neuronal fate. Further, PAPCs also displayed morphologically neuronal maturation by an increasing axonal/dendritic complexity over time. Therefore, PAPCs seem to undergo a molecular and morphological maturation program similar to that observed during adult neurogenesis. We provide evidence that neuronal gene expression of PAPCs was not a consequence of cell fusion with maternal neurons. In addition, in mothers with experimentally induced Parkinson's disease (PD), the frequency of PAPCs within the hippocampus initially increased whereas long-term presence of PAPCs was compromised. Also, the spatial distribution of PAPCs within the hippocampus was altered in mothers with PD. Thus, the disease context influenced the initial attraction, long-term survival, and spatial distribution of PAPCs, which may have wider implications on cell replacement strategies in human neurodegenerative diseases such as PD.
    Stem cells and development 12/2010; 19(12):1819-30. · 4.15 Impact Factor
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    ABSTRACT: Stimulation of the subiculum/CA1 of the hippocampal formation evokes monosynaptic field potentials in the prefrontal cortex (PFC). High-frequency stimulation of the hippocampus (HPC) can induce long-term potentiation (LTP) in this hippocampo-prefrontal cortical (hippo-PFC) pathway. Previous studies have shown that dopamine and serotonin modulate hippo-PFC LTP. Here, we investigated whether the locus coeruleus (LC) and noradrenaline (NA) can modulate LTP in the rat hippo-PFC pathway. Stimulation of the LC in combination with stimulation of the HPC increased hippo-PFC LTP. Infusion of lidocaine into the LC reduced hippo-PFC LTP. Administration of the noradrenaline reuptake inhibitor, nisoxetine or the alpha2 adrenoceptor antagonist, idazoxan prior to high-frequency stimulation of the HPC enhanced hippo-LTP. In contrast, administration of clonidine, an alpha2 adrenoceptor agonist, impaired hippo-PFC LTP. Partial noradrenergic (NAergic) lesioning with DSP-4 also impaired hippo-PFC LTP. In conclusion, the LC and NAergic mechanisms modulate hippo-PFC LTP.
    The International Journal of Neuropsychopharmacology 10/2010; 13(9):1219-31. · 5.64 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra (SN). The present study was designed to examine the therapeutic effect of hydrogen sulfide (H(2)S, a novel biological gas) on PD. The endogenous H(2)S level was markedly reduced in the SN in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Systemic administration of NaHS (an H(2)S donor) dramatically reversed the progression of movement dysfunction, loss of tyrosine-hydroxylase positive neurons in the SN and the elevated malondialdehyde level in injured striatum in the 6-OHDA-induced PD model. H(2)S specifically inhibited 6-OHDA evoked NADPH oxidase activation and oxygen consumption. Similarly, administration of NaHS also prevented the development of PD induced by rotenone. NaHS treatment inhibited microglial activation in the SN and accumulation of pro-inflammatory factors (e.g. TNF-alpha and nitric oxide) in the striatum via NF-kappaB pathway. Moreover, significantly less neurotoxicity was found in neurons treated with the conditioned medium from microglia incubated with both NaHS and rotenone compared to that with rotenone only, suggesting that the therapeutic effect of NaHS was, at least partially, secondary to its suppression of microglial activation. In summary, we demonstrate for the first time that H(2)S may serve as a neuroprotectant to treat and prevent neurotoxin-induced neurodegeneration via multiple mechanisms including anti-oxidative stress, anti-inflammation and metabolic inhibition and therefore has potential therapeutic value for treatment of PD.
    Aging cell 04/2010; 9(2):135-46. · 7.55 Impact Factor

Publication Stats

649 Citations
179.00 Total Impact Points

Institutions

  • 2014
    • National University Health System
      Singapore
  • 2005–2013
    • National University of Singapore
      • Department of Pharmacology
      Singapore, Singapore
  • 2009
    • Kunming Medical College
      Yün-nan, Yunnan, China
    • Clinical Research Center of Moscow
      Moskva, Moscow, Russia
  • 2008
    • The University of Hong Kong
      Hong Kong, Hong Kong
  • 2007–2008
    • Institute of Molecular Biology
      Mayence, Rheinland-Pfalz, Germany
  • 2004–2008
    • Singapore General Hospital
      • Department of Clinical Research
      Tumasik, Singapore