The role of translocator protein in olfactory mucosa neurogenesis and behavior

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.