Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models.
Philipp MewsAshley M CunninghamJoseph ScarpaAarthi RamakrishnanEmily M HicksSarah BolnickSusanna GaramszegiLi ShenDeborah C MashEric J NestlerPublished in: Science advances (2023)
Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from men suffering from CUD and matched controls. Weighted gene coexpression analyses identified CUD-specific gene networks enriched in ionotropic receptors and linked to lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity.
Keyphrases
- public health
- single cell
- copy number
- genome wide
- prefrontal cortex
- genome wide identification
- end stage renal disease
- rna seq
- functional connectivity
- multiple sclerosis
- resting state
- endothelial cells
- white matter
- newly diagnosed
- traumatic brain injury
- chronic kidney disease
- ejection fraction
- spinal cord
- parkinson disease
- cerebral ischemia
- computed tomography
- oxidative stress
- magnetic resonance imaging
- spinal cord injury
- case report
- diabetic rats
- high glucose
- network analysis
- genome wide analysis
- dna methylation
- lipopolysaccharide induced
- brain injury
- systemic lupus erythematosus
- drug induced
- lps induced
- subarachnoid hemorrhage
- middle aged
- pluripotent stem cells