Affective phenotypes in heterozygous LRRK2 R1441G knock-in mice

Area of Science:

• Neuroscience
• Genetics
• Behavioral Science

Background:

• Missense mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene are associated with familial Parkinson's disease (PD).
• LRRK2 mutant mouse models often lack motor deficits, leaving non-motor symptoms understudied.

Purpose of the Study:

• To investigate the behavioral impact of the LRRK2 R1441G missense mutation, focusing on non-motor symptoms in heterozygous knock-in (KI) mice.
• To explore potential affective and cognitive alterations in a preclinical model of PD.

Main Methods:

• Utilized heterozygous R1441G knock-in (KI) mice and wild-type (WT) littermates.
• Assessed behavioral despair using the forced swim test (FST).
• Evaluated anhedonia via sucrose preference tests and anxiety levels in the elevated plus maze.

Main Results:

• Heterozygous R1441G KI mice exhibited increased behavioral despair and anhedonia.
• These mice showed reduced anxiety in the elevated plus maze, suggesting a dominant-negative effect.
• No significant alterations were observed in cognitive, social, or motor domains.

Conclusions:

• The LRRK2 R1441G mutation may selectively affect affective dimensions in prodromal adult mice.
• The observed phenotypes suggest a dominant-negative impact on anxiety and depressive-like behaviors.
• Further research is needed to elucidate the mechanisms behind these domain-specific effects.