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Adamson SX, Zheng W, Agim ZS, et al. Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance. Biomolecules. 2021;11(9)doi: 10.3390/biom11091315.
Adamson, S. X., Zheng, W., Agim, Z. S., Du, S., Fleming, S., Shannahan, J., & Cannon, J. (2021). Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance. Biomolecules, 11(9), . https://doi.org/10.3390/biom11091315
Adamson, Sherleen Xue-Fu, et al. "Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance." Biomolecules vol. 11,9 (2021). doi: https://doi.org/10.3390/biom11091315
Adamson SX, Zheng W, Agim ZS, Du S, Fleming S, Shannahan J, Cannon J. Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance. Biomolecules. 2021 Sep 06;11(9). doi: 10.3390/biom11091315. PMID: 34572528; PMCID: PMC8471899.
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Biomolecules. 2021 Sep 06;11(9). doi: 10.3390/biom11091315.

Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance.

Biomolecules

Sherleen Xue-Fu Adamson, Wei Zheng, Zeynep Sena Agim, Sarah Du, Sheila Fleming, Jonathan Shannahan, Jason Cannon

Affiliations

  1. School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
  2. Purdue Institute for Integrative Neurosciences, Purdue University, West Lafayette, IN 47907, USA.
  3. Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA.

PMID: 34572528 PMCID: PMC8471899 DOI: 10.3390/biom11091315

Abstract

Disrupted systemic copper (Cu) homeostasis underlies neurodegenerative diseases with early symptoms including olfactory dysfunction. This study investigated the impact of Cu dyshomeostasis on olfactory function, adult neurogenesis, and neurochemical balance. Models of Cu deficiency (CuD) and Cu overload (CuO) were established by feeding adult rats with Cu-restricted diets plus ip. injection of a Cu chelator (ammonium tetrathiomolybdate) and excess Cu, respectively. CuD reduced Cu levels in the olfactory bulb (OB), subventricular zone (SVZ), rostral migratory stream (RMS), and striatum, while CuO increased Cu levels in these areas. The buried pellet test revealed both CuD and CuO prolonged the latency to uncover food. CuD increased neural proliferation and stem cells in the SVZ and newly differentiated neurons in the OB, whereas CuO caused opposite alterations, suggesting a "switch"-type function of Cu in regulating adult neurogenesis. CuO increased GABA in the OB, while both CuD and CuO reduced DOPAC, HVA, 5-HT and the DA turnover rate in olfactory-associated brain regions. Altered mRNA expression of Cu transport and storage proteins in tested brain areas were observed under both conditions. Together, results support an association between systemic Cu dyshomeostasis and olfactory dysfunction. Specifically, altered adult neurogenesis along the SVZ-RMS-OB pathway and neurochemical imbalance could be the factors that may contribute to olfactory dysfunction.

Keywords: Cu deficiency; Cu overload; GABA; adult neurogenesis; neurochemical homeostasis; olfactory; rostral migratory stream; subventricular zone

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