Translocator protein (TSPO) is an 18 kDa mitochondrial protein involved in mitochondrial function, steroidogenesis, apoptosis, and inflammation, and is widely used as an imaging biomarker in Alzheimer’s disease. Baseline levels of TSPO are generally low in healthy adult brains except for within neurogenic niches like the olfactory bulb and hippocampus, where its function is poorly understood. Here, we investigated the role of TSPO in olfactory neurogenesis and behavior in rats.
TSPO is localized predominantly to olfactory sensory neurons in the olfactory bulb and mucosa. Single-cell RNA sequencing revealed that Tspo-knockout (KO) dysregulated protein synthesis, mitochondrial respiration, and altered neuronal differentiation in olfactory sensory neurons and their progenitors. In vitro, Tspo-KO impaired mitochondrial respiration and ATP production in primary olfactory stem cells, subsequently contributing to a decrease in mature neuron markers on cultured differentiation.
Deletion of TSPO in rats also resulted in behavioral deficits in recognition memory and olfactory performance, which can be in part linked to these cellular impairments. These findings identify TSPO as a regulator of olfactory neurogenesis and energy metabolism, providing insight into mechanisms that may underlie olfactory deficits. We thank Chantal Sottas (University of Southern California) for assisting with the breeding of animals and collection of rodent tissues.
This work was supported by funds from the Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences and the John Stauffer Dean’s Chair in Pharmaceutical Sciences (University of Southern California). Department of Pharmacology and Pharmaceutical Sciences, Alfred E.
Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA Garett Cheung, Yiqi Christina Lin & Vassilios Papadopoulos Correspondence to Vassilios Papadopoulos. The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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