Intranasal deferoxamine can improve memory in healthy C57 mice, suggesting a partially non‐disease‐specific pathway of functional neurologic improvement
| Autor: | Katherine A. Faltesek, Jacob Kosyakovsky, Jared M. Fine, Aleta L. Svitak, Leah R. Hanson, Jacob M. Cooner, Amanda M. Baillargeon, William H. Frey, Julian Tokarev |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Disease specific Siderophores Water maze Deferoxamine Pharmacology 050105 experimental psychology lcsh:RC321-571 Mice 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Memory improvement medicine Animals 0501 psychology and cognitive sciences Dosing Neurologic disease lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Administration Intranasal Original Research Glycogen Synthase Kinase 3 beta Working memory business.industry intranasal 05 social sciences Brain Hypoxia-Inducible Factor 1 alpha Subunit hypoxia‐inducible factor 1α Memory Short-Term glycogen synthase kinase 3β radial arm water maze Nasal administration business 030217 neurology & neurosurgery memory enhancement medicine.drug |
| Zdroj: | Brain and Behavior Brain and Behavior, Vol 10, Iss 3, Pp n/a-n/a (2020) |
| ISSN: | 2162-3279 |
| Popis: | Introduction Intranasal deferoxamine (IN DFO) has been shown to decrease memory loss and have beneficial impacts across several models of neurologic disease and injury, including rodent models of Alzheimer's and Parkinson's disease. Methods In order to assess the mechanism of DFO, determine its ability to improve memory from baseline in the absence of a diseased state, and assess targeting ability of intranasal delivery, we treated healthy mice with IN DFO (2.4 mg) or intraperitoneal (IP) DFO and compared behavioral and biochemical changes with saline‐treated controls. Mice were treated 5 days/week for 4 weeks and subjected to behavioral tests 30 min after dosing. Results We found that IN DFO, but not IP DFO, significantly enhanced working memory in the radial arm water maze, suggesting that IN administration is more efficacious as a targeted delivery route to the brain. Moreover, the ability of DFO to improve memory from baseline in healthy mice suggests a non‐disease‐specific mechanism of memory improvement. IN DFO treatment was accompanied by decreased GSK‐3β activity and increased HIF‐1α activity. Conclusions These pathways are suspected in DFO's ability to improve memory and perhaps represent a component of the common mechanism through which DFO enacts beneficial change in models of neurologic disease and injury. Intranasal deferoxamine (IN DFO) decreases memory loss and has beneficial impacts across several models of neurologic disease and injury. We show that IN DFO improves memory from baseline in normal healthy mice while modifying GSK‐3β and HIF‐1α, suggesting these pathways may be involved in a common mechanism through which DFO enacts beneficial change. |
| Databáze: | OpenAIRE |
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