Back to Search
Start Over
Cognitive impairments following cranial irradiation can be mitigated by treatment with a tropomyosin receptor kinase B agonist.
- Source :
-
Experimental neurology [Exp Neurol] 2016 May; Vol. 279, pp. 178-186. Date of Electronic Publication: 2016 Mar 02. - Publication Year :
- 2016
-
Abstract
- Brain radiotherapy is frequently used successfully to treat brain tumors. However, radiotherapy is often associated with declines in short-term and long-term memory, learning ability, and verbal fluency. We previously identified a downregulation of the brain-derived neurotrophic factor (BDNF) following cranial irradiation in experimental animals. In the present study, we investigated whether targeting the BDNF high affinity receptor, tropomysin receptor kinase B (TrkB), could mitigate radiation-induced cognitive deficits. After irradiation, chronic treatment with a small molecule TrkB agonist, 7,8-dihydroxyflavone (DHF) in mice led to enhanced activation of TrkB and its downstream targets ERK and AKT, both important factors in neuronal development. DHF treatment significantly restored spatial, contextual, and working memory, and the positive effects persisted for at least 3months after completion of the treatment. Consistent with preservation of cognitive functions, chronic DHF treatment mitigated radiation-induced suppression of hippocampal neurogenesis. Spine density and major components of the excitatory synapses, including glutamate receptors and postsynaptic density protein 95 (PSD-95), were also maintained at normal levels by DHF treatment after irradiation. Taken together, our results show that chronic treatment with DHF after irradiation significantly mitigates radiation-induced cognitive defects. This is achieved most likely by preservation of hippocampal neurogenesis and synaptic plasticity.<br /> (Published by Elsevier Inc.)
- Subjects :
- Animals
Brain-Derived Neurotrophic Factor biosynthesis
Down-Regulation radiation effects
Flavones pharmacology
Hippocampus pathology
Hippocampus radiation effects
Male
Memory, Short-Term drug effects
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase Kinases drug effects
Neurogenesis radiation effects
Neuronal Plasticity drug effects
Oncogene Protein v-akt drug effects
Radiation Injuries pathology
Receptors, Glutamate drug effects
Spatial Memory drug effects
Synapses drug effects
Synapses radiation effects
Brain radiation effects
Cognition Disorders drug therapy
Cognition Disorders etiology
Radiation Injuries drug therapy
Receptor, trkB agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2430
- Volume :
- 279
- Database :
- MEDLINE
- Journal :
- Experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 26946222
- Full Text :
- https://doi.org/10.1016/j.expneurol.2016.02.021