Ping Liu

Ping Liu
University of Otago · Department of Anatomy

PhD

About

96
Publications
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Publications

Publications (96)
Article
Full-text available
l-arginine is a versatile amino acid with a number of bioactive metabolites. Increasing evidence implicates altered arginine metabolism in the aging and neurodegenerative processes. The present study, for the first time, determined the effects of sex and estrous cycle on the brain and blood (plasma) arginine metabolic profile in naïve rats. Female...
Article
Synapse dysfunction is an integral feature of Alzheimer’s disease (AD) pathophysiology. In fact, prodromal manifestation of structural and functional deficits in synapses much prior to appearance of overt pathological hallmarks of the disease indicates that AD might be considered as a degenerative disorder of the synapses. Several research instrume...
Article
Amyloid-beta (Aβ) cleaved from amyloid precursor protein (APP) has been proposed to play a central and causative role in the aetiology of Alzheimer’s disease (AD). APPswe/PSEN1dE9 (APP/PS1) transgenic mice display chronic Aβ accumulation and deposition in the brain. L-arginine is a semi-essential amino acid with a number of bioactive metabolites, a...
Article
During pregnancy, fetal thyroid hormones (THs) are dependent on maternal placental transport and their physiological level is crucial for normal fetal neurodevelopment. Earlier research has shown that Di-(2-ethylhexyl) phthalate (DEHP) disrupts thyroid function and THs homeostasis in pregnant women and fetuses, and affects placental THs transport....
Article
Thallium (Tl), a ubiquitous environmental toxicant, can cross the placental barrier during pregnancy. However, the effects of prenatal Tl exposure on placental function are currently unclear. Based on the Ma'anshan Birth Cohort study, we examined whether long-term prenatal Tl exposure was associated with placental inflammation. Tl concentrations we...
Article
Full-text available
Agmatine (decarboxylated arginine) exerts numerous central nervous system (CNS) dependent pharmacological effects and may potentially modulate altered neurochemistry seen in neurological disorders. In preclinical studies, injection has been the predominant route of systemic administration. However, a significant translational step would be the use...
Article
Full-text available
Tauopathies consist of intracellular accumulation of hyperphosphorylated and aggregated microtubule protein tau, which remains a histopathological feature of Alzheimer’s disease (AD) and frontotemporal dementia. l-Arginine is a semi-essential amino acid with a number of bioactive molecules. Its downstream metabolites putrescine, spermidine, and spe...
Article
Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is a key regulator of cerebral blood flow (CBF) dynamics. Mice with eNOS deficiency (eNOS−/-) display age-related increases in amyloid beta in the brain and memory deficits, implicating eNOS dysfunction in the neuropathogenesis and/or development of Alzheimer's disease (AD). The present s...
Poster
Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO) from L-arginine, and eNOS derived NO is a key regulator of cerebral blood flow dynamics. It has been proposed that cerebrovascular endothelial dysfunction during advanced aging, together with other risk factors, may trigger the neurodegenerative processes in Alzheimer’s disease (AD...
Article
Microglia, the resident immune cells in the central nervous system, play critical roles in neurodevelopment, synaptic pruning and neuronal wiring. Early in development, microglia migrate via the tangential and radial migration pathways to their final destinations and mature gradually, a process that includes morphological changes. Recent research h...
Conference Paper
Full-text available
Background: Recent research suggests that cerebrovascular endothelial dysfunction during advanced aging, together with other risk factors, may trigger the neurodegenerative processes in Alzheimer’s disease (AD). AD brains display dramatically reduced protein expression of endothelial nitric oxide synthase (eNOS)and excessive amounts of ammonia and...
Article
Full-text available
While amyloid-beta (Aβ) peptides play a central role in the development of Alzheimer’s disease (AD), recent evidence also implicates altered metabolism of L-arginine in the pathogenesis of AD. The present study systematically investigated how behavioural function and the brain and plasma arginine metabolic profiles changed in a chronic Aβ accumulat...
Article
Full-text available
Accumulating evidence suggests that altered arginine metabolism is involved in the aging and neurodegenerative processes. This study sought to determine the effects of age and vitamin E supplementation in the form of tocotrienol-rich fraction (TRF) on brain arginine metabolism. Male Wistar rats at ages of 3 and 21 months were supplemented with TRF...
Article
Neuronal nitric oxide synthase (nNOS) is a key arginine metabolising enzyme in the brain, and nNOS-derived nitric oxide plays an important role in regulating glutamatergic neurotransmission. Nitric oxide and its related molecules are involved in the pathogenesis of schizophrenia, and human genetic studies have identified schizophrenia risk genes en...
Article
l-Arginine is a versatile semi-essential amino acid with a number of bioactive metabolites, and altered arginine metabolism has been implicated in the pathogenesis of schizophrenia. Earlier research has demonstrated that maternal immune activation (MIA; a risk factor for schizophrenia) alters arginine metabolism in the prefrontal cortex and hippoca...
Article
Some studies have demonstrated that aging is associated with impaired vestibular reflexes, especially otolithic reflexes, resulting in postural instability. However, the neurochemical basis of these age-related changes is still poorly understood. The L-arginine metabolic system has been implicated in changes in the brain associated with aging. In t...
Article
Phencyclidine (PCP) induces behavioural changes in humans and laboratory animals that resemble positive and negative symptoms, and cognitive impairments in schizophrenia. It has been shown repeated treatment of PCP leading to persistent symptoms even after the drug discontinuation, and there is a growing body of evidence implicating altered arginin...
Article
Full-text available
Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizoph...
Article
During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in...
Article
While amyloid beta (Aβ) plays a central role in the development of Alzheimer's disease (AD), recent evidence suggests the involvement of arginine metabolism in AD pathogenesis. Earlier research has shown that a single intracerebroventricular (i.c.v.) infusion of pre-aggregated Aβ25-35 (the neurotoxic domain of the full-length Aβ) altered arginine m...
Article
Phencyclidine (PCP), a non-competitive N-methyl-D-aspartate glutamate receptor antagonist, induces schizophrenic symptoms in healthy individuals, and altered arginine metabolism has been implicated in schizophrenia. The present study investigated the effects of a single subcutaneous injection of PCP (2, 5 or 10 mg/kg) on arginine metabolism in the...
Article
Regression is a common statistical tool for prediction in neuroscience. However, linear regression is by far the most common form of regression used, with regression trees receiving comparatively little attention. In this study, the results of conventional multiple linear regression (MLR) were compared with those of random forest regression (RFR),...
Article
Accumulating evidence suggests that the metabolism of L-arginine, a metabolically versatile amino acid, is critically involved in the aging process. The present study compared the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of L-arginine and its eight down-stream metabolites in the brain stem (pons an...
Article
Full-text available
Agmatine (decarboxylated arginine) has been known as a natural product for over 100 years, but its biosynthesis in humans was left unexplored owing to long-standing controversy. Only recently has the demonstration of agmatine biosynthesis in mammals revived research, indicating its exceptional modulatory action at multiple molecular targets, includ...
Article
Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during aging. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioral function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study...
Article
A growing body of evidence suggests the involvement of l-arginine and its metabolites in the ageing and neurodegenerative processes. The present study assessed behavioural performance in 4- (young), 12- (middle-aged) and 24- (aged) month-old male Sprague-Dawley rats, and investigated age-related changes in the activity of two key arginine metabolic...
Article
L-arginine, a semi-essential amino acid, can be metabolized to form a number of bioactive molecules. Nitric oxide (NO), generated by NO synthase (NOS) from L-arginine, has been strongly implicated in the aging process. Agmatine, decarboxylated arginine, regulates the production of NO and other metabolites of L-arginine, modulates behavioural functi...
Article
L-arginine, one of the most metabolically versatile amino acids, can be metabolized to form a number of bioactive molecules. The present study systematically investigated age-related changes in L-arginine and its metabolites in the hippocampus, parahippocampal region, and prefrontal cortex at the tissue (crude homogenates) and synaptoneurosome (a s...
Article
Recent evidence suggests that polyamines putrescine, spermidine and spermine are essential in maintaining normal cellular function. The present study investigated the effects of chronic treatment of difluoromethylornithine (DFMO, 3% in drinking water), a potent inhibitor of putrescine synthesis, for 54 consecutive days on animals'behavior and neuro...
Article
Alzheimer's disease (AD) is a neurodegenerative disorder with progressive memory loss. It has been shown that the cholinergic neurotransmission deficit is one of the neurochemical characteristics of AD, and that L-arginine and its metabolites also play a prominent role in AD pathogenesis. Scopolamine, a non-selective muscarinic receptor antagonist,...
Article
Amyloid beta (Aβ) has been proposed to play a central and causative role in the development of Alzheimer's disease. Aβ(25-35), the neurotoxic domain of the full-length Aβ, causes learning and memory impairments in rodents. The present study investigated the effects of a single bilateral i.c.v. infusion of pre-aggregated Aβ(25-35) (30 nmol/rat) on a...
Article
Agmatine, the decarboxylated metabolite of l-arginine, is considered to be a novel putative neurotransmitter. Recent studies have demonstrated that endogenous agmatine may directly participate in the processes of spatial learning and memory. Agmatine-immunoreactivity has been observed within synaptic terminals of asymmetric excitatory synapses in t...
Article
Agmatine, a metabolite of L-arginine, is considered as a novel putative neurotransmitter. It has been detected in axon terminals that synapse with pyramidal cells in the hippocampus, a brain region that is critically involved in spatial learning and memory. However, the role of agmatine in learning and memory is poorly understood. Recently, we demo...
Article
Aging is associated with neurochemical changes in the brain that result in impaired vestibular reflex function. We analysed the concentrations of 9 related neurochemicals (l-arginine, l-citrulline, l-ornithine, agmatine, putrescine, spermidine, spermine, glutamate and gamma-aminobutyric acid (GABA)) in the vestibular nucleus of aged (24 months old)...
Article
Amyloid beta fragment 25-35 (Abeta(25-35)) is the neurotoxic domain of the full-length Abeta(1-42) and causes memory impairments in rodents. Recent research suggests that agmatine, decarboxylated arginine, has a neuroprotective role. This study investigated the effects of a single bilateral i.c.v. infusion of aggregated Abeta(25-35) (30 nmol) in a...
Article
The present study systematically investigated the effects of agmatine administered i.p. in several commonly used behavioral tasks. In Experiment 1, pre-test treatment of agmatine (1 and 40 mg/kg) appeared to improve animals' performance in the water maze probe test conducted 24 h, but not 120 s, after training, when the effect was evaluated within...
Article
L-arginine is metabolised by nitric oxide synthase (NOS) and arginase to form L-citrulline and nitric oxide, and L-ornithine and urea, respectively. The present study investigated NOS and arginase activities, and the levels of L-arginine, L-citrulline and L-ornithine, as well as glutamate and gamma-aminobutyric acid (GABA), in memory-related brain...
Article
L-citrulline, L-ornithine, and agmatine are the metabolites of L-arginine by nitric oxide synthase (NOS), arginase, and arginine decarboxylase (ADC), respectively. In contrast to the NOS and arginase pathways, the role of the ADC-agmatine pathway in learning and memory has only been paid attention lately. Recent evidence suggests a potential involv...
Article
It has been long known that the physiological concentrations of polyamines putrescine, spermidine and spermine are essential for cell growth. However, the role of endogenous polyamines in behavior function is poorly understood at present. This study investigated animals' behavioral performance and neurochemical changes in the hippocampus and prefro...
Article
Recent evidence suggests that agmatine, the metabolite of arginine by arginine decarboxylase, exists in the mammalian brain and is a novel neurotransmitter. Exogenous agmatine can modulate behaviour function, including learning and memory. The present study investigated the effects of repeated i.c.v. microinfusion of agmatine (once daily) on the re...
Article
The postrhinal cortex (POR) receives input from parietal cortex and sends output to the hippocampus. It may, therefore, relay spatial information to the hippocampus and as a result, lesions of POR may disturb the spatial firing patterns of hippocampal place cells. To test this hypothesis, the firing of hippocampal CA1 place cells in rats with bilat...
Article
Accumulating evidence suggests that agmatine, a metabolite of L-arginine by arginine decarboxylase, is a novel neurotransmitter, and exogenous agmatine can modulate behavior functions including learning and memory. However, direct evidence of its involvement in learning and memory processes is currently lacking. This study measured agmatine levels...
Article
We investigated regional variations and the effects of aging on the expression of the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor subunits in several memory-associated structures using Western blotting. In young adult rats, NR1, NR2A, and GluR2 levels varied between the hippocampus and parahippocampal...
Article
Agmatine is a metabolite of L-arginine by arginine decarboxylase. Recent evidence suggests that it exists in mammalian brain and is a novel neurotransmitter. The present study measured agmatine levels in several memory-associated brain structures in aged (24-month-old), middle-aged (12-month-old), and young (4-month-old) male Sprague Dawley rats us...
Article
Polyamines putrescine, spermidine and spermine are positively charged aliphatic amines and have important roles in maintaining normal cellular function, regulating neurotransmitter receptors and modulating learning and memory. Recent evidence suggests a role of putrescine in hippocampal neurogenesis, that is significantly impaired during aging. The...
Article
The present study investigated the behavioral effects of intracerebroventricular microinfusion of agmatine. Rats with low dose (10 microg), but not high dose (100 microg), of agmatine spent significantly less time in the enclosed arm and more time in the open arm in the elevated plus maze. In the water maze task, the high dose group displayed a tra...
Article
Full-text available
Interest in interaction between the vestibular system and the hippocampus was stimulated by evidence that peripheral vestibular lesions could impair performance in learning and memory tasks requiring spatial information processing. By the 1990s, electrophysiological data were emerging that the brainstem vestibular nucleus complex (VNC) and the hipp...
Article
It has been suggested that vestibular compensation, the process of behavioural recovery that occurs following peripheral vestibular damage, might be partially dependent on the release of glucocorticoids (GC) during the early stages of recovery from the lesion. One possibility is that glucocorticoid receptors (GRs) in the vestibular nucleus complex...
Article
The present study investigated age-related changes in nitric oxide synthase (NOS) and arginase in the subregions of the hippocampus and their correlations with animals' performance in the open field, T-maze, and water maze tasks. Aged rats (24 months old) showed reduced exploratory activity and poorer spatial learning relative to the young adults (...
Article
CB1 receptor expression has been reported to be low in the brainstem compared with the forebrain, and low in the vestibular nucleus complex (VNC) compared with other regions in the brainstem. However, a frequent effect of cannabis is dizziness and loss of balance. This may be due to the activation of cannabinoid receptors in the central vestibular...
Article
The present study investigated age-related changes in nitric oxide synthase (NOS) and arginase, which shares a substrate with NOS, in the hippocampus and parahippocampal region and the relationship between NOS/arginase and age-associated behavioural impairments. Aged rats (24 months old) displayed reduced exploratory activity, enhanced anxiety, poo...
Article
Increasing evidence suggests that nitric oxide (NO), generated by nitric oxide synthase (NOS) from l-arginine, plays an important role in the ageing process. The present study, for the first time, investigates age-related changes in NOS and arginase, an enzyme that shares a common substrate with NOS, in the prefrontal cortex of rats assessed with a...
Article
Full-text available
Previous studies have shown that peripheral vestibular damage causes long-term neurochemical changes in the hippocampus which may be related to spatial memory deficits. Since recent studies have also demonstrated deficits in non-spatial object recognition memory following vestibular lesions, the aim of the present study was to extend these investig...
Article
To determine what influence the pre- and parasubiculum regions of the hippocampal formation have on neural representations within the dorsal hippocampus, single-unit recordings were made as rats with bilateral ibotenic acid lesions centered on the former regions (n = 4) or control surgeries (n = 3) foraged freely. Spatial firing specificity was mea...
Article
Cannabinoids have been shown to disrupt memory processes and these effects occur primarily through cannabinoid CB1 receptors in the brain. The present study investigates, for the first time, the regional variations and age-related changes in CB1 protein expression in the hippocampus and its neighbouring entorhinal, perirhinal, postrhinal and tempor...
Article
The aim of this study was to investigate the possible relationship between changes in neuronal and endothelial nitric oxide synthase (nNOS and eNOS) and arginase expression in the vestibular nucleus complex and the hippocampus (CA1, CA2/3 and the dentate gyrus (DG) at 10 h or 2 weeks following a unilateral vestibular deafferentation (UVD) in rats....
Article
L-arginine can be metabolised by nitric oxide synthase (NOS) with the formation of L-citrulline and nitric oxide (NO), or arginase with the production of L-ornithine and urea. In contrast to studies showing a potential involvement of NOS/NO in the aging process, the role of arginase has not been well documented. The present study investigates for t...
Article
Previous studies have indicated that damage to the peripheral vestibular system results in dysfunction of hippocampal place cells and an impairment of spatial learning and memory. The aim of this study was to determine whether lesions of one vestibular labyrinth (unilateral vestibular deafferentation, UVD) result in changes in the expression of the...
Article
The integrity of the perirhinal cortex is critical for certain types of learning and memory. One important issue relating to the function of this region is its interaction with other brain areas that play a role in memory processing. This study investigates the time course of changes in activity and protein expression of nitric oxide synthase (NOS)...
Article
Increasing evidence suggests that nitric oxide synthase (NOS)/nitric oxide (NO) contributes to the aging process. By contrast, the role of arginase, which shares a common substrate with NOS, has not been determined. In the present study, regional variations and age-related changes in NOS and arginase in the hippocampus and its neighboring structure...
Article
Full-text available
Rats with bilateral N-methyl-D-aspartate lesions centered on the postrhinal cortex (POR) and sham lesions were tested in a series of spatial memory tasks. The POR-lesioned rats were significantly impaired compared with sham rats in the reference memory version of both the water maze and radial arm maze tasks and in the standard radial arm maze work...