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Effect of ethanol and cocaine on [11C]MPC-6827 uptake in SH-SY5Y cells.
Damuka, Naresh; Orr, Miranda; Czoty, Paul W; Weiner, Jeffrey L; Martin, Thomas J; Nader, Michael A; Bansode, Avinash H; Liyana Pathirannahel, Buddhika S; Mintz, Akiva; Macauley, Shannon L; Craft, Suzanne; Solingapuram Sai, Kiran Kumar.
Afiliação
  • Damuka N; Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Orr M; Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Czoty PW; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Weiner JL; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Martin TJ; Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Nader MA; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Bansode AH; Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Liyana Pathirannahel BS; Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Mintz A; Department of Radiology, Columbia University Medical Center, New York, NY, USA.
  • Macauley SL; Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Craft S; Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Solingapuram Sai KK; Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA. ksolinga@wakehealth.edu.
Mol Biol Rep ; 48(4): 3871-3876, 2021 Apr.
Article em En | MEDLINE | ID: mdl-33880672
Microtubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [11C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [11C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [11C]MPC-6827 may have high affinity to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [11C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin units). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs and Alzheimer's disease.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinazolinas / Cocaína / Compostos Radiofarmacêuticos / Etanol Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinazolinas / Cocaína / Compostos Radiofarmacêuticos / Etanol Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article