AAV-Parkin-hWT-Rat

General Information

Rat: Wistar

 The full-length human Parkin gene is expressed unilaterally in the SN of rats using Adeno-Associated virus 2/8 (AAV2/8).

Endogenous Parkin: Yes

Corresponding human genotype:  Parkin was the first gene associated with autosomal recessive Parkinson’s disease (PD).

Targeted gene: Parkin

References: Van Rompuy 2014

Viral injection

Injection coordinates: Right SN -. one deposition site : AP − 5.3 mm, ML −2.0 mm rel and DV −7.2 mm surface.

Volume of injection and viral titer: three microliters of AAV2/8 vector is injected at a concentration of 2 × 10¹¹ GC/ml

Transgene expression

4 and 12 days then 1, 2, 4 and 8 months post-injection: The transgene is expressed in neurons of the SN and ventral tegmental are (VTA); very little expression is detected in astrocytes and microglia cells. The volume of the transduced area is maximal after 12 days and gradually decreases thereafter.

Neurodegeneration

4 and 12 days then 1, 2, 4 and 8 months post-injection: Loss of TH- positive neurons in the SN is visible 2 months post-injection and increases over time. A similar loss of VMAT2 is observed (immunostaining). The loss of TH positive projections is maximal at 4 months and a partial recovery is observed 8 months post-injection.

Dopamine Homeostasis

Not reported

Inclusions

Not reported

Motor Behaviours

4 days then 1, 2, 4 and 8 months post-injection: Transgenic animals exhibit a bias in the use of forelimb paws in the cylinder test at 4 months; a recovery is observed at 8 months.

Response to dopaminergic treatment

Not reported

Non-motor Behaviours

Not reported

Electrophysiology

Not reported

Neuroinflammation

4 days and 1 month: An increased inflammation is observed mostly along the needle track (CD68 staining) in the rats expressing the human Parkin gene after a month,