Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

Oliveros, Alfredo; Starski, Phillip; Lindberg, Daniel M.; Choi, Sun Hee; Heppelmann, Carrie J.; Dasari, Surendra; Choi, Doo Sup

doi:10.1021/acs.jproteome.6b00830

Cited by 10 publications

(10 citation statements)

References 62 publications

(124 reference statements)

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“…2a and Supplementary Data 2). Within these sexually dimorphic proteins, we identified proteins previously implicated in reward-and drug-associated responses, such as GRM2 22 , VPS51 23 , SATT 24 , VGLU3 25 , IPO4 26 , VAMP1 27 , and CYFP2 28 (Fig. 2b).…”

Section: Resultsmentioning

confidence: 99%

Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens

et al. 2021

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Substance use disorder (SUD) is a chronic neuropsychiatric condition characterized by long-lasting alterations in the neural circuitry regulating reward and motivation. Substantial work has focused on characterizing the molecular substrates that underlie these persistent changes in neural function and behavior. However, this work has overwhelmingly focused on male subjects, despite mounting clinical and preclinical evidence that females demonstrate dissimilar progression to SUD and responsivity to stimulant drugs of abuse, such as cocaine. Here, we show that sex is a critical biological variable that defines drug-induced plasticity in the nucleus accumbens (NAc). Using quantitative mass spectrometry, we assessed the protein expression patterns induced by cocaine self-administration and demonstrated unique molecular profiles between males and females. We show that 1. Cocaine self-administration induces non-overlapping protein expression patterns in significantly regulated proteins in males and females and 2. Critically, cocaine-induced protein regulation differentially interacts with sex to eliminate basal sexual dimorphisms in the proteome. Finally, eliminating these baseline differences in the proteome is concomitant with the elimination of sex differences in behavior for non-drug rewards. Together, these data suggest that cocaine administration is capable of rewriting basal proteomic function and reward-associated behaviors.

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Section: Resultsmentioning

confidence: 99%

Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens

et al. 2021

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“…Phenylalanine is an essential amino acid highly concentrated in brain and precursor for the neurotransmitter called catecholamines 43 . Adenosine, composed of adenine and d-ribose, plays a role in signal transduction as a neurotransmitter 44 . Inosine is a purine nucleoside that is an intermediate in the degradation of purines and purine nucleosides like hypoxanthine and also occurs in the anticodon of certain transfer RNA molecules.…”

Section: Discussionmentioning

confidence: 99%

Comparative metabolomics study on therapeutic mechanism of electro-acupuncture and moxibustion on rats with chronic atrophic gastritis (CAG)

Liu

Chen

Chang

et al. 2017

Sci Rep

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Some studies have proved that both acupuncture and moxibustion are very effective for the treatment of CAG. However, little is known about therapeutic mechanism of electro-acupuncture and moxibustion on CAG as well as the difference between them. On the other hand, metabolomics is a ‘top-down’ approach to understand metabolic changes of organisms caused by disease or interventions in holistic context, which consists with the holistic thinking of electro-acupuncture and moxibustion treatment. In this study, the difference of therapeutic mechanism between electro-acupuncture and moxibustion on CAG rats was investigated by a 1H NMR-based metabolomics analysis of multiple biological samples (serum, stomach, cerebral cortex and medulla) coupled with pathological examination and molecular biological assay. For all sample types, both electro-acupuncture and moxibustion intervention showed beneficial effects by restoring many CAG-induced metabolic changes involved in membrane metabolism, energy metabolism and function of neurotransmitters. Notably, the moxibustion played an important role in CAG treatment mainly by regulating energy metabolism in serum, while main acting site of electro-acupuncture treatment was nervous system in stomach and brain. These findings are helpful to facilitate the therapeutic mechanism elucidating of electro-acupuncture and moxibustion on CAG rats. Metabolomics is promising in mechanisms study for traditional Chinese medicine (TCM).

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“…Mice ( Grk3 +/+ n = 4, Grk3 −/− n = 4) were anesthetized with isoflurane and brains immediately removed, washed in ice-cold 1x PBS, and the prefrontal cortex (PFC) was subsequently dissected, snap-frozen on dry ice and stored at −80 °C until analysis. Tissue was prepared and label-free proteomics was performed as previously described [ 35 , 36 ]. To determine the effects of GRK3 deletion on canonical pathways and disease processes we utilized Ingenuity Pathway Analysis (IPA), see also Supplementary Information.…”

Section: Methodsmentioning

confidence: 99%

GRK3 deficiency elicits brain immune activation and psychosis

et al. 2021

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The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3−/− mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1β, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3−/− mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.

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Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

Cited by 10 publications

References 62 publications

Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens

Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens

Comparative metabolomics study on therapeutic mechanism of electro-acupuncture and moxibustion on rats with chronic atrophic gastritis (CAG)

GRK3 deficiency elicits brain immune activation and psychosis

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