Intracerebral administration of a modified antisense oligonucleotide targeting the dopamine system in a mouse model of Parkinson's disease

STAR Protoc. 2022 Jun 10;3(2):101445. doi: 10.1016/j.xpro.2022.101445. eCollection 2022 Jun 17.

Abstract

Here, we present an optimized protocol for generating a mouse model overexpressing human α-synuclein in dopamine (DA) neurons driven by an adeno-associated viral (AAV) vector and for the examination of the benefit of an antisense oligonucleotide (ASO)-based therapy on DA neurotransmission under Parkinson's disease (PD)-like conditions. We describe AAV injection, followed by implantation of an osmotic minipump for ASO delivery and a guide cannula for microdialysis to measure DA release. This protocol can be used to evaluate oligonucleotide-based therapies for PD. For complete details on the use and execution of this protocol, please refer to Alarcón-Arís et al. (2020).

Keywords: Cell Biology; Health Sciences; Model Organisms; Neuroscience; Protein Biochemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dopamine / physiology
  • Dopaminergic Neurons
  • Mice
  • Oligonucleotides
  • Oligonucleotides, Antisense / therapeutic use
  • Parkinson Disease* / genetics

Substances

  • Oligonucleotides
  • Oligonucleotides, Antisense
  • Dopamine