Biphenotypic Cells and α-Synuclein Accumulation in Enteric Neurons of Leucine-Rich Repeat Kinase 2 Knockout Mice

• Published in: Digestive diseases and sciences Vol. 69; no. 8; pp. 2828 - 2840
• Main Authors: Maekawa, Tatsunori, Motokawa, Ryuichi, Kawashima, Rei, Tamaki, Shun, Hara, Yusuke, Kawakami, Fumitaka, Ichikawa, Takafumi
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2024; Springer Nature B.V
• Subjects: alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Animals; Biochemistry; Enteric Nervous System - metabolism; Gastroenterology; Hepatology; Kinases; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - metabolism; Medicine; Medicine & Public Health; Mice; Mice, Knockout; Myenteric Plexus - metabolism; Nervous system; Neuroglia - metabolism; Neurons - metabolism; Oncology; Original Article; Phenotype; Transplant Surgery; α-Synuclein; Enteric nervous system; Parkinson’s disease; Lrrk2
• ISSN: 0163-2116; 1573-2568; 1573-2568
• DOI: 10.1007/s10620-024-08494-7

Background Leucine-rich repeat kinase 2 is a molecule that is responsible for familial Parkinson’s disease. Our previous findings revealed that leucine-rich repeat kinase 2 is expressed in the enteric nervous system. However, which cells in the enteric nervous system express leucine-rich repeat kinase 2 and whether leucine-rich repeat kinase 2 is associated with the structure of the enteric nervous system remain unclear. The enteric nervous system is remarkable because some patients with Parkinson’s disease experience gastrointestinal symptoms before developing motor symptoms. Aims We established a leucine-rich repeat kinase 2 reporter mouse model and performed immunostaining in leucine-rich repeat kinase 2 knockout mice. Methods Longitudinal muscle containing the myenteric plexus prepared from leucine-rich repeat kinase 2 reporter mice was analyzed by immunostaining using anti-green fluorescent protein (GFP) antibody. Immunostaining using several combinations of antibodies characterizing enteric neurons and glial cells was performed on intestinal preparations from leucine-rich repeat kinase 2 knockout mice. Results GFP expression in the reporter mice was predominantly in enteric glial cells rather than in enteric neurons. Immunostaining revealed that differences in the structure and proportion of major immunophenotypic cells were not apparent in the knockout mice. Interestingly, the number of biphenotypic cells expressing the neuronal and glial cell markers increased in the leucine-rich repeat kinase 2 knockout mice. Moreover, there was accumulation of α-synuclein in the knockout mice. Conclusions Our present findings suggest that leucine-rich repeat kinase 2 is a newly recognized molecule that potentially regulates the integrity of enteric nervous system and enteric α-synuclein accumulation. Graphical Abstract