Lipidomic changes in the rat hippocampus following cocaine conditioning, extinction, and reinstatement of drug‐seeking

Pati, Sumitra; Angel, Peggi; Drake, Richard; Wagner, John J.; Cummings, Brian S.

doi:10.1002/brb3.1451

Cited by 7 publications

(3 citation statements)

References 38 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, results from MOFA suggested gene expression changes related to the electron transport chain as another key metabolic pathway alteration. This is supported by findings from animal models of cocaine addiction where a downregulation of glycolysis and oxidative phosphorylation were observed in the brain 52 while fatty acid metabolism genes were upregulated 53 . It has to be noted that metabolic changes in CUD are most likely not brain-spercific but also appear on a systemic level as individuals with CUD were found to have reduced body fat in comparison to a healthy control group 54 .…”

Section: Discussionsupporting

confidence: 64%

Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder

Zillich,

Belschner,

Avetyan

et al. 2024

Preprint

View full text Add to dashboard Cite

Structural and functional changes of the brain are assumed to contribute to excessive cocaine intake, craving, and relapse in cocaine use disorder (CUD). Epigenetic and transcriptional changes were hypothesized as a molecular basis for CUD-associated brain alterations. Here we performed a multi-omics study of CUD by integrating epigenome-wide methylomic (N=42) and transcriptomic (N=25) data from the same individuals using postmortem brain tissue of Brodmann Area 9 (BA9). Of the N=1,057 differentially expressed genes (p<0.05), one gene, ZFAND2A, was significantly upregulated in CUD at transcriptome-wide significance (q<0.05). Differential alternative splicing (AS) analysis revealed N=98 alternatively spliced transcripts enriched in axon and dendrite extension pathways. Strong convergent overlap in CUD-associated expression deregulation was found between our BA9 cohort and independent replication datasets. Epigenomic, transcriptomic, and AS changes in BA9 converged at two genes, ZBTB4 and INPP5E. In pathway analyses, synaptic signaling, neuron morphogenesis, and fatty acid metabolism emerged as the most prominently deregulated biological processes. Drug repositioning analysis revealed glucocorticoid receptor targeting drugs as most potent in reversing the CUD expression profile. Our study highlights the value of multi-omics approaches for an in-depth molecular characterization and provides insights into the relationship between CUD-associated epigenomic and transcriptomic signatures in the human prefrontal cortex.

show abstract

Section: Discussionsupporting

confidence: 64%

Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder

Zillich,

Belschner,

Avetyan

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…It is reasonable to be the same case with cocaine exposure. Brain region-specific increased expressions of mitochondrial biogenesis-related genes were found in a rat cocaine abuse model [ 51 ]. However, there is limited evidence to measure the exact performance of neuronal mitochondrial biogenesis after cocaine exposure.…”

Section: The Neurotoxicity Of Cocainementioning

confidence: 99%

Role of Mitochondrial Dynamics in Cocaine’s Neurotoxicity

Wen

Aki

Funakoshi

et al. 2022

IJMS

View full text Add to dashboard Cite

The dynamic balance of mitochondrial fission and fusion maintains mitochondrial homeostasis and optimal function. It is indispensable for cells such as neurons, which rely on the finely tuned mitochondria to carry out their normal physiological activities. The potent psychostimulant cocaine impairs mitochondria as one way it exerts its neurotoxicity, wherein the disturbances in mitochondrial dynamics have been suggested to play an essential role. In this review, we summarize the neurotoxicity of cocaine and the role of mitochondrial dynamics in cellular physiology. Subsequently, we introduce current findings that link disturbed neuronal mitochondrial dynamics with cocaine exposure. Finally, the possible role and potential therapeutic value of mitochondrial dynamics in cocaine neurotoxicity are discussed.

show abstract

“…Mass spectrometry imaging (MSI) is a powerful tool for spatial interrogation of altered lipid biochemistry as a result of disease or exposure to exogenous compounds such as cocaine. , One of the MSI techniques, time-of-flight secondary ion mass spectrometry (ToF-SIMS), has been increasingly used in bioimaging to explore the lipid molecular architecture of cells and tissues . Given the high complexity and heterogeneity of the brain, it is essential to obtain detailed spatial organization in order to gain the insight of the relations between the molecular structure and function of the brain.…”

Section: Introductionmentioning

confidence: 99%

Interplay between Cocaine, Drug Removal, and Methylphenidate Reversal on Phospholipid Alterations in Drosophila Brain Determined by Imaging Mass Spectrometry

Philipsen¹,

Phan

Fletcher

et al. 2020

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Cocaine dependence displays a broad impairment in cognitive performance including attention, learning, and memory. To obtain a better understanding of the action of cocaine in the nervous system, and the relation between phospholipids and memory, we have investigated whether phospholipids recover in the brain following cocaine removal using the fly model, Drosophila melanogaster. In addition, the effects of methylphenidate, a substitute medication for cocaine dependence, on fly brain lipids after cocaine abuse are also determined to see if it can rescue the lipid changes caused by cocaine. Time of flight secondary ion mass spectrometry with a (CO2)6000 + gas cluster ion beam was used to detect intact phospholipids. We show that cocaine has persistent effects, both increasing and decreasing the levels of specific phosphatidylethanolamines and phosphatidylinositols. These changes remain after cocaine withdrawal and are not rescued by methylphenidate. Cocaine is again shown to generally increase the levels of phosphatidylcholines in the fly brain; however, after drug withdrawal, the abundance of these lipids returns to the original level and methylphenidate treatment of the flies following cocaine exposure enhances the reversal of the lipid level reducing them below the original control. The study provides insight into the molecular effects of cocaine and methylphenidate on brain lipids. We suggest that phosphatidylcholines could be a potential target for the treatment of cocaine abuse as well as be a significant hallmark of cognition and memory loss with cocaine.

show abstract

Lipidomic changes in the rat hippocampus following cocaine conditioning, extinction, and reinstatement of drug‐seeking

Cited by 7 publications

References 38 publications

Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder

Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder

Role of Mitochondrial Dynamics in Cocaine’s Neurotoxicity

Interplay between Cocaine, Drug Removal, and Methylphenidate Reversal on Phospholipid Alterations in Drosophila Brain Determined by Imaging Mass Spectrometry

Contact Info

Product

Resources

About