Topographic distribution of dopamine D2 receptors in the human inferior olivary nucleus in control, Alzheimer’s disease, and Parkinson’s disease cases

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Abstract The inferior olivary nucleus (IO), the source of climbing fibers, is a key component of olivocerebellar circuitry involved in motor coordination and learning, and its broader contribution to higher-order cerebellar functions remains of growing interest. Although the neurochemical organization of the human IO has been partially described, the distribution of dopamine D2 receptors (D2R) within this nucleus has not previously been characterized. In the present study, we investigated the topographic distribution of D2R immunoreactivity in the human IO in neurological control, Alzheimer’s disease (AD), and Parkinson’s disease (PD) cases using immunoperoxidase and immunofluorescence staining. D2R immunoreactivity displayed a punctate pattern throughout the IO and was observed across its major subregions. Quantitative analysis revealed a significantly greater D2R-immunoreactive area in AD cases than in controls, whereas no significant regional differences were detected among the examined IO subregions. These findings provide the first description of D2R distribution in the human IO and extend current knowledge of its chemoarchitectural organization. The increased D2R immunoreactivity observed in AD suggests that the olivary dopaminergic microenvironment may be altered in neurodegenerative disease. Given the limited number of PD cases, however, these observations should be regarded as preliminary, and further studies in larger cohorts are needed to clarify the potential relevance of D2R-related changes in the human IO.

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