Adult neurogenesis as a mediator of antidepressant action and cognitive side effects of brain tumor therapy
Prosjekt
- Prosjektnummer
- 46053400
- Ansvarlig person
- Ayumu Tashiro
- Institusjon
- NTNU, INM
- Prosjektkategori
- korttidsprosjekt 2011
- Helsekategori
- Mental Health
- Forskningsaktivitet
- 1. Underpinning
Rapporter
We investigated the role of adult neurogenesis in mediating side effects associated with brain tumor therapies such as depression and impaired cognition. The original project description was written for three year project application, which was rejected and funded as one year project. This was why we decided to focus on establishing a protocol of Temozolomide application in 2011.
Since the start of the project, we have tested injection protocols. TMZ was injected i.p. (2,5 mg/ml in 0.9% NaCl) on three consecutive days of a week for 4 weeks (Garthe et al., PLoS One 4:1-13, 2009). At the start of the fifth week BrdU was injected (50 mg/kg i.p.) and mice were sacrificed five days later. Immature neurons were detected by immunostaining for BrdU and doublecortin (DCX). TMZ injected mice showed 18,8% reduction in BrdU positive cells (p<0,05) and 45,5% reduction in DCX positive cells (p<0,001). Thus we confirmed that our protocol causes effective reduction in adult neurogenesis.
We have also established behavioral procedure using touch screen behavioral equipment in order to examine pattern separation/cognitive flexibility ability in mice. Mice achieve more than 80% accuracy in the task within one month of training period.
Next step will be combining these two established protocol in order to examine roles of adult neurogenesis in cognitive flexibility. We have applied for continued funding from Kontaktutvalget one year project,but not successful.
Although we sought additional funding, we were not able to get it. Unfortunately, the project is currently on hold due to lack of financial support.
However, if the project is successfully performed, there is a possibility to show that adult neurogenesis is involved in mild cognitive impairment associated with cancer therapy. Such realization would initiate better therapeutic method to consider preservation of adult neurogenesis in patients to prevent side effects such as cognitive impairment.
Cognitive impairment is a major side effect associated with anti-cancer treatments. A common mechanism of anti-cancer treatment is to block cell division in order to suppress tumor growth, which may interfere neurogenesis in adult brain. We investigate the role of adult neurogenesis in mediating side effects associated with brain tumor therapies.We investigates the role of adult neurogenesis in mediating side effects associated with brain tumor therapies such as depression and impaired cognition. The original project description was written for three year project application, which was rejected and funded as one year project. This was why we decided to focus on establishing a protocol of Temozolomide application in 2011 and hope that we will get continued funding after 2012.
Since the start of the project, we have tested injection protocols. TMZ was injected i.p. (2,5 mg/ml in 0.9% NaCl) on three consecutive days of a week for 4 weeks (Garthe et al., PLoS One 4:1-13, 2009). At the start of the fifth week BrdU was injected (50 mg/kg i.p.) and mice were sacrificed five days later. Immature neurons were detected by immunostaining for BrdU and doublecortin (DCX). TMZ injected mice showed 18,8% reduction in BrdU positive cells (p<0,05) and 45,5% reduction in DCX positive cells (p<0,001). Thus we confirmed that our protocol causes effective reduction in adult neurogenesis.
We have also established behavioral procedure using touch screen behavioral equipment in order to examine pattern separation/cognitive flexibility ability in mice. Mice achieve more than 80% accuracy in the task within one month of training period.
Next step will be combining these two established protocol in order to examine roles of adult neurogenesis in cognitive flexibility by testing mice with or without TMZ treatment using this behavioral task. We have applied for continued funding from Kontaktutvalget one year project. Unfortunately funding has not been allocated to my application so far, but hope that the funding will be allocated to allow us to continue the project. We will also look into other opportunities to get research funding to complete this project.
eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT
Alle henvendelser rettes til Helse Midt-Norge RHF - Samarbeidsorganet og FFU