The effects of long-term atorvastatin use on the cytoarchitecture of new and older neurons of sensorimotor nucleus HVC in a juvenile songbird model
Year: 2017
Type: preprint
Abstract: Statins are widely prescribed and highly efficacious cholesterol lowering drugs. Due to their success in lowering serum cholesterol in adults, the Food and Drug Administration approved four statins, including atorvastatin, for pediatric populations at risk for high cholesterol in 2007. Some statins are known to cross the blood brain barrier and impact cholesterol regulation in the brain. Cholesterol is an important component of all cell membranes, and altering levels of membrane cholesterol has been shown to affect cell structure and function. Thus it is critical to evaluate the effects of long-term statin use on neural substrates. Here we used a songbird model to study the effects of long-term statin use on neurogenesis and cytoarchitechture of new neurons in vivo in a zebra finch songbird model system. Birds received either 40 mg/kg of atorvastatin in water, or water, as juveniles until adulthood. We then labeled newborn cells using bromodeoxyuridine (BrdU) and used immunohistochemistry to visualize BrdU and the neuron-specific protein Hu. We found that neuronal morphology differed between statin-treated birds and controls. In statin-treated birds, BrdU+/Hu+ neuronal somas were flatter and had more furrowed contours relative to controls. BrdU-/Hu+ neuronal somas (putatively older neurons) were smaller in statin-treated birds than controls. No differences in the numbers of new neurons were observed. We suggest that atorvastatin may be affecting neural cytoarchitecture as a consequence of arresting cholesterol synthesis in the brain.
DOI: 10.1101/196204
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2766080354