Leptin Receptor Expression in Mouse Intracranial Perivascular Cells

Area of Science:

• Neuroscience
• Cell Biology
• Endocrinology

Background:

• Previous research indicated non-neuronal cells in the brain express leptin receptors, but their specific types and locations were unclear.
• The long form of the leptin receptor (LepRb) is crucial for leptin signaling, but its non-neuronal expression patterns require detailed investigation.

Purpose of the Study:

• To identify and map the distribution of leptin receptor-expressing non-neuronal cells within the adult mouse brain.
• To investigate the role of LepRb in meningeal perivascular cells and its potential connection to brain diseases.

Main Methods:

• Utilized a LepRb-Cre^tdTomato reporter mouse model to permanently label LepRb-expressing cells.
• Performed double immunohistochemistry for neuronal (NeuN) and cell-specific markers (vitronectin, PDGFBR).
• Conducted in situ hybridization and qPCR to analyze leptin receptor and associated gene expression in meninges and hypothalamus.

Main Results:

• The majority of tdTomato-positive cells were neurons, but non-neuronal tdTomato-positive cells were found in the choroid plexus and perivascular spaces.
• Perivascular cells, identified as pericytes expressing vitronectin and PDGFBR, were enriched in leptin receptor mRNA.
• LepRb-deficient mice showed altered expression of vitronectin and PDGFBR in meninges and hypothalamus.

Conclusions:

• Meningeal perivascular cells, integral to the blood-brain barrier, are the primary intracranial non-neuronal cells expressing LepRb in adult mice.
• Pericytic leptin signaling may be vital for maintaining intracranial perivascular space integrity.
• This finding offers a potential link between obesity, leptin signaling, and the pathogenesis of various brain diseases.