General Information
Rat: Sprague-Dawley
Expression of the mutant (E46K) human alpha-synuclein protein using the bacterial artificial chromosome (BAC) in rat.
Endogenous rat alpha synuclein: Yes
Corresponding human genotype: Autosomal dominant mutation in PD patients
Transgene insertion: chromosome 11
Reference: Cannon 2013
Transgene expression
- 12 months: diffuse expression of the transgene is observed throughout the brain, in particular in the olfactory bulb, frontal cortex, striatum, ventral midbrain and cerebral cortex. A low expression is also detected in the spinal cord.
Neurodegeneration
- 6 months: Increased sensitivity of dopaminergic terminals (but not of neurons) to low-dose rotenone treatment is detected.
- 12 months: No changes in DAT density is observed suggesting that there is no nigral neurodegeneration.
Dopamine Homeostasis
- 12 months: no depletion of dopamine is observed; a reduction in the levels of dopamine metabolites indicates a decrease in dopamine turnover. Reduced serotoninergic turnover is also detected.
Inclusions
- 12 months: accumulation of abnormal alpha-synuclein is detected in TH-positive neurons in the SN and VTA, striatum (in processes), cortex (in processes). Intracellular accumulation seems limited to dopaminergic neurons.
Motor Behaviours
- Not reported
Response to L-DOPA treatment
- Not reported
Non motor Behaviours
- Not reported
Electrophysiology
- Not reported
Neuroinflammation
- Not reported