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Spatial multiomic i...
Spatial multiomic insights into acute cocaine exposure
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- Nezhyva, Mariya (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Jansson group
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Shahen, Samah (author)
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Kabirova, Marina (author)
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Bentov-Arav, Einav (author)
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Shalev, Ori (author)
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- Andrén, Per E., Professor, 1957- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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Thornton, Claire (author)
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Yaka, Rami (author)
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Margulis, Katherine (author)
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- Jansson, Erik T., Docent, tekn. dr. 1984- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
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- Recent studies provide compelling evidence that cocaine-induced neurotoxicity begins within hours of a single acute cocaine exposure. Despite this, a comprehensive understanding of the molecular alterations occurring in vivo within the reward system following such an exposure has been lacking. In this study, we developed an analytical workflow that combines mass spectrometry imaging with microscale proteomics of brain regions. Here, we present a multiomic perspective on the molecular consequences of acute cocaine exposure on the principal areas of the reward system and the hippocampus. Our findings include distinct region-specific alterations in the tricarboxylic acid (TCA) cycle and lipid synthesis within the reward circuitry highlighting a significant energy depletion in mice 24 hours post-cocaine injections. Additionally, we linked widespread reductions in key neurotransmitters (GABA, glutamate, aspartate) across the reward system and calcium level modifications to changes in synaptic plasticity and mitochondria dysfunction. Mitochondrial dysfunction and energy metabolism disruption were evident through imbalances in the mitochondrial ATP production and electron transport chain components, increased susceptibility to oxidative stress, disturbances in mitochondrial transport proteins, and fluctuations in creatine and taurine levels. Among the brain regions within the reward circuitry, the prefrontal cortex (PFC) exhibited the most pronounced effects. This study not only provides a holistic overview of the intricate interplay between proteins and metabolites within the reward circuitry regions during the onset of cocaine-induced neurotoxicity but also offers novel insights into the underlying molecular mechanisms.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Beroendelära (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Substance Abuse (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- Biological Research on Drug Dependence
- Biologisk beroendeforskning
Publication and Content Type
- vet (subject category)
- ovr (subject category)
To the university's database
- By the author/editor
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Nezhyva, Mariya
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Shahen, Samah
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Kabirova, Marina
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Bentov-Arav, Ein ...
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Shalev, Ori
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Andrén, Per E., ...
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Thornton, Claire
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Yaka, Rami
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Margulis, Kather ...
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Jansson, Erik T. ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Health Sciences
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and Substance Abuse
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
- By the university
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Uppsala University