Brain Sciences (Mar 2024)

A Pilot Study on a Possible Mechanism behind Olfactory Dysfunction in Parkinson’s Disease: The Association of TAAR1 Downregulation with Neuronal Loss and Inflammation along Olfactory Pathway

  • Mei-Xuan Zhang,
  • Hui Hong,
  • Yun Shi,
  • Wen-Yan Huang,
  • Yi-Meng Xia,
  • Lu-Lu Tan,
  • Wei-Jiang Zhao,
  • Chen-Meng Qiao,
  • Jian Wu,
  • Li-Ping Zhao,
  • Shu-Bing Huang,
  • Xue-Bing Jia,
  • Yan-Qin Shen,
  • Chun Cui

DOI
https://doi.org/10.3390/brainsci14040300
Journal volume & issue
Vol. 14, no. 4
p. 300

Abstract

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Parkinson’s disease (PD) is characterized not only by motor symptoms but also by non-motor dysfunctions, such as olfactory impairment; the cause is not fully understood. Our study suggests that neuronal loss and inflammation in brain regions along the olfactory pathway, such as the olfactory bulb (OB) and the piriform cortex (PC), may contribute to olfactory dysfunction in PD mice, which might be related to the downregulation of the trace amine-associated receptor 1 (TAAR1) in these areas. In the striatum, although only a decrease in mRNA level, but not in protein level, of TAAR1 was detected, bioinformatic analyses substantiated its correlation with PD. Moreover, we discovered that neuronal death and inflammation in the OB and the PC in PD mice might be regulated by TAAR through the Bcl-2/caspase3 pathway. This manifested as a decrease of anti-apoptotic protein Bcl-2 and an increase of the pro-apoptotic protein cleaved caspase3, or through regulating astrocytes activity, manifested as the increase of TAAR1 in astrocytes, which might lead to the decreased clearance of glutamate and consequent neurotoxicity. In summary, we have identified a possible mechanism to elucidate the olfactory dysfunction in PD, positing neuronal damage and inflammation due to apoptosis and astrocyte activity along the olfactory pathway in conjunction with the downregulation of TAAR1.

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