Metformin Pretreatment Rescues Subependymal Zone Neurogenesis and Long-Term Olfactory Memory in a Juvenile Model of Cranial Irradiation
Year: 2019
Type: dissertation
Abstract: Neural stem cells (NCSs) in the mammalian brain contribute to neurogenesis throughout life and in response to brain injuries to promote neurorepair. Cranial irradiation (IR), used as an adjuvant therapy in the treatment of childhood brain tumors, results in cognitive deficits associated with long-term impairments to neurogenesis in rodent models. Metformin is an antidiabetic drug that enhances functional neurogenesis under physiological conditions and in response to brain injuries. Herein, we investigated metformin’s potential to rescue deficits to neurogenesis and long-term olfactory memory (LTOM) following cranial IR. Juvenile mice displayed acute and persistent deficits in periventricular neurogenesis following 8 Gy cranial IR. We show that metformin pretreatment was sufficient to enhance the recovery of proliferating neuroblasts and completely restore LTOM. This study is the first to report that metformin pretreatment promotes neurogenesis and functional recovery following juvenile cranial IR and supports its consideration as a therapeutic intervention to enhance neurorepair.
Source: TSpace (University of Toronto)
Author: Daniel Derkach
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3044140223