A Metabolomic Study of Brain Tissues from Aged Mice with Low Expression of the Vesicular Monoamine Transporter 2 (VMAT2) Gene

Salek, Reza M.; Colebrooke, Rebecca E.; Macintosh, Robin L.; Lynch, Patrick J.; Sweatman, Brian C.; Emson, Piers C.; Griffin, Julian L.

doi:10.1007/s11064-007-9542-3

Cited by 24 publications

(26 citation statements)

References 39 publications

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“…The preparation of brain samples was based on previous studies [18], [19]. Briefly, the frozen tissue with 0.8 ml of ultrapure water was homogenized by using Branson Sonifier (Japan) for 2 min (200 W) at 4°C, and 0.8 ml ice-cold chloroform was added into the homogenate.…”

Section: Methodsmentioning

confidence: 99%

Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

Bu²,

Chen³

et al. 2014

PLoS ONE

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Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP) models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. 1H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc) and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

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Section: Methodsmentioning

confidence: 99%

Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

Bu²,

Chen³

et al. 2014

PLoS ONE

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“…Specimens of bilateral brain hippocampus, NAc, PFC and striatum (~30-100 mg) were dissected immediately, snap-frozen in liquid nitrogen, and stored at -80°C until NMR spectroscopic analysis. The preparation of the brain samples was based on the previous studies [18,19]. The frozen tissue was added into 0.5 ml chloroform and homogenized at 4°C.…”

Section: Methodsmentioning

confidence: 99%

1H-Nuclear magnetic resonance-based metabolomic analysis of brain in mice with nicotine treatment

Chen

Shao

et al. 2014

BMC Neurosci

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BackgroundNicotine is rapidly absorbed from cigarette smoke and therefore induces a number of chronic illnesses with the widespread use of tobacco products. Studies have shown a few cerebral metabolites modified by nicotine; however, endogenous metabolic profiling in brain has not been well explored.ResultsH NMR-based on metabonomics was applied to investigate the endogenous metabolic profiling of brain hippocampus, nucleus acumens (NAc), prefrontal cortex (PFC) and striatum. We found that nicotine significantly increased CPP in mice, and some specific cerebral metabolites differentially changed in nicotine-treated mice. These modified metabolites included glutamate, acetylcholine, tryptamine, glucose, lactate, creatine, 3-hydroxybutyrate and nicotinamide-adenine dinucleotide (NAD), which was closely associated with neurotransmitter and energy source. Additionally, glutathione and taurine in hippocampus and striatum, phosphocholine in PFC and glycerol in NAc were significantly modified by nicotine, implying the dysregulation of anti-oxidative stress response and membrane metabolism.ConclusionsNicotine induces significant metabonomic alterations in brain, which are involved in neurotransmitter disturbance, energy metabolism dysregulation, anti-oxidation and membrane function disruptions, as well as amino acid metabolism imbalance. These findings provide a new insight into rewarding effects of nicotine and the underlying mechanism.

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“…To account for differences in sample volumes, each integrated region was normalised to the total spectral area for all integral regions in that spectrum, excluding water and TSP resonances. Spectra were assigned by comparison with assignment tables (Lindon et al 1999; Govindaraju et al 2000; Pears et al 2005; Salek et al 2008; Salek et al 2010) and on-line databases (http://www.bmrb.wisc.edu/metabolomics and http://mmcd.nmrfam.wisc.edu) such that metabolites contributing to each bin were defined.…”

Section: Methodsmentioning

confidence: 99%

A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

et al. 2011

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The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in γ-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1–2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.

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A Metabolomic Study of Brain Tissues from Aged Mice with Low Expression of the Vesicular Monoamine Transporter 2 (VMAT2) Gene

Cited by 24 publications

References 39 publications

Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

1H-Nuclear magnetic resonance-based metabolomic analysis of brain in mice with nicotine treatment

A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

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