| First Author | Ohki T | Year | 2025 |
| Journal | Front Neurosci | Volume | 19 |
| Pages | 1688394 | PubMed ID | 41425066 |
| Mgi Jnum | J:387189 | Mgi Id | MGI:8272987 |
| Doi | 10.3389/fnins.2025.1688394 | Citation | Ohki T, et al. (2025) Depletion of CD169(+) border-associated macrophages induces Parkinson's disease-like behavior. Front Neurosci 19:1688394 |
| abstractText | Parkinson's disease (PD) and Alzheimer's disease (AD) present with complex behavioral symptoms that can arise in the absence of overt structural brain damage. Recent evidence suggests that border-associated macrophages (BAMs) located at the brain's interfaces regulate central nervous system function, yet the specific roles of distinct BAM subsets remain largely undefined. By reanalyzing single-nucleus RNA sequencing data from postmortem PD brains, we identified a BAM subset expressing CD169 that was significantly reduced in patients compared with controls. To examine their function, we employed CD169-DTR mice to selectively ablate CD169(+) BAMs and evaluated behavioral and histological changes. Depletion of CD169(+) BAMs induced tremors, abnormal hindlimb reflexes, and heightened anxiety-like behavior without dopaminergic neuron loss. Histological analysis revealed a pronounced reduction of mitral and tufted cells in the olfactory bulb, indicating disruption of olfactory-limbic circuitry. These findings demonstrate that CD169(+) BAMs are critical for maintaining neural network stability and motor function, and that their loss can elicit PD-like phenotypes in the absence of classical dopaminergic neurodegeneration. This work establishes a novel mouse model linking brain-border immune cell dysfunction to Parkinsonian pathology and highlights a neuroimmune mechanism that may contribute to the onset of PD-like disorders. |
