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Drugs targeting intermediate filaments can improve neurosupportive properties of astrocytes.
de Pablo, Yolanda; Chen, Meng; Möllerström, Elin; Pekna, Marcela; Pekny, Milos.
Affiliation
  • de Pablo Y; Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: yolanda.depablo@neuro.gu.se.
  • Chen M; Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Möllerström E; Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Pekna M; Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; University of Newcastle, New South Wale
  • Pekny M; Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; University of Newcastle, New South Wale
Brain Res Bull ; 136: 130-138, 2018 01.
Article in En | MEDLINE | ID: mdl-28159699
In response to central nervous system (CNS) injury, astrocytes upregulate intermediate filament (nanofilament) proteins GFAP and vimentin. Whereas the intermediate filament upregulation in astrocytes is important for neuroprotection in the acute phase of injury, in some contexts it might inhibit some of the regenerative processes later on. Thus, timely modulation of the astrocyte intermediate filaments was proposed as a strategy to promote brain repair. We used clomipramine, epoxomicin and withaferin A, drugs reported to decrease the expression of GFAP, and assessed their effect on neurosupportive properties and resilience of astrocytes to oxygen and glucose deprivation (OGD). Clomipramine decreased protein levels of GFAP, as well as vimentin and nestin, and did not affect astrocyte resilience to oxidative stress. Withaferin A sensitized astrocytes to OGD. Both clomipramine and epoxomicin promoted the attachment and survival of neurons co-cultured with astrocytes under standard culture conditions. Moreover, epoxomicin increased neurosupportive properties of astrocytes after OGD. Our data point to clomipramine and epoxomicin as potential candidates for astrocyte modulation to improve outcome after CNS injury.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Intermediate Filaments / Astrocytes / Clomipramine / Neuroprotective Agents / Withanolides Limits: Animals Language: En Journal: Brain Res Bull Year: 2018 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Intermediate Filaments / Astrocytes / Clomipramine / Neuroprotective Agents / Withanolides Limits: Animals Language: En Journal: Brain Res Bull Year: 2018 Document type: Article Country of publication: