Nasal neuron PET imaging quantifies neuron generation and degeneration
Genevieve C. Van de Bittner, … , Mark W. Albers, Jacob M. Hooker
Genevieve C. Van de Bittner, … , Mark W. Albers, Jacob M. Hooker
Published January 23, 2017
Citation Information: J Clin Invest. 2017;127(2):681-694. https://doi.org/10.1172/JCI89162.
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Research Article Aging Neuroscience

Nasal neuron PET imaging quantifies neuron generation and degeneration

Abstract

Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality. Notably, OSNs are continually replenished by adult neurogenesis in mammals, including humans, so OSN measurements are primed to provide specialized insights into neurological disease. Here, we have evaluated a PET radiotracer, [11C]GV1-57, that specifically binds mature OSNs and quantifies the mature OSN population in vivo. [11C]GV1-57 monitored native OSN population dynamics in rodents, detecting OSN generation during postnatal development and aging-associated neurodegeneration. [11C]GV1-57 additionally measured rates of neuron regeneration after acute injury and early-stage OSN deficits in a rodent tauopathy model of neurodegenerative disease. Preliminary assessment in nonhuman primates suggested maintained uptake and saturable binding of [18F]GV1-57 in primate nasal epithelium, supporting its translational potential. Future applications for GV1-57 include monitoring additional diseases or conditions associated with olfactory dysregulation, including cognitive decline, as well as monitoring effects of neuroregenerative or neuroprotective therapeutics.

Authors

Genevieve C. Van de Bittner, Misha M. Riley, Luxiang Cao, Janina Ehses, Scott P. Herrick, Emily L. Ricq, Hsiao-Ying Wey, Michael J. O’Neill, Zeshan Ahmed, Tracey K. Murray, Jaclyn E. Smith, Changning Wang, Frederick A. Schroeder, Mark W. Albers, Jacob M. Hooker

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Figure 5

[11C]GV1-57 imaging of early-symptomatic mature OSN neurodegeneration in a murine tauopathy model.

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[11C]GV1-57 imaging of early-symptomatic mature OSN neurodegeneration in...
(A) Representative [11C]GV1-57 PET images (SUV, NIH+white, 3–45 minutes) of female rTg4510 and WT (within colony) mice at 3.7 and 7 months of age. Mice were administered [11C]GV1-57 (0.51 ± 0.091 mCi) and imaged for 60 minutes. (B) DVR quantification of [11C]GV1-57 uptake in WT control and rTg4510 animals. Error bars are ± SEM; n = 4 per group. *P < 0.05, ***P < 0.005 using a 2-tailed Student’s t test. (C) Immunoblot quantification of the mature OSN population (OMP) in WT and rTg4510 animals at 3.7 and 7 months of age. Immunoblot intensities were multiplied by total protein extracted per sample and normalized to the mean of the WT 3.7-month values to determine relative mature OSN populations. Error bars are ± SEM; n = 4 per group. *P < 0.05 using a 2-tailed Student’s t test. NS, P = 0.26 using a 2-tailed Student’s t test. (D) OE thickness measurements from paired (within age) septal OE regions. OE regions were paired by OE depth and OE subregion, i.e., the dorsal or medial portion of the septum. Error bars are ± SEM; n = 6–8 regions per group. **P < 0.01 using a 2-tailed, paired Student’s t test.