Association between olfactory loss and cognitive deficits in Parkinson's disease

Park

Int Forum Allergy Rhinol

et al. 2019

Background Several studies have reported the benefits of olfactory training (OT) in the olfactory nervous system of mouse models. Therefore, in this study we performed next‐generation sequencing to evaluate the effects of OT on mRNA sequencing in the olfactory area. Methods Mice in each group were administered 300 mg of 3‐methylindole per kilogram of mouse weight. The olfactory function was evaluated by a food‐finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis. Subsequently, data analysis, gene ontology and pathway analysis, quantitative real‐time polymerase chain reaction of mRNA, and Western blot analysis were conducted. Results Mice were divided into 4 groups according to treatment. Control, anosmia, training, and steroid group mice resumed food finding. Olfactory Maker Protein, olfr1507, ADCY3, and GNAL mRNA expression was higher in the olfactory neuroepithelium of OT than anosmia group mice. In total, 26,364 mRNAs were analyzed. Comparison of the results of OT vs anosmia revealed that ADCY8,10, GFAP, NGF, NGFR, GFAP, and BDNF mRNAs were upregulated in the gene ontology. Conclusion OT improved olfactory function, as indicated by the food‐finding test. OT improved the olfactory recovery time to stimulate olfactory nerve regeneration. OT may initially stimulate the olfactory receptor, followed by neurogenesis. Steroid therapy and OT operated under completely different mechanisms in the upregulated gene study. These results indicate that OT may be one of the future modalities for treating olfactory impairment.

Section: Discussionmentioning

confidence: 99%

The neuroplastic effect of olfactory training to the recovery of olfactory system in mouse model

Park

Int Forum Allergy Rhinol

et al. 2019

“…The use of shared neural substrates in the premotor frontal and orbitofrontal cortex by olfaction and cognition (Figure 2), and the contribution of cholinergic deficits to OD provides a potential mechanism for why greater OD appears to identify the subset of sporadic and monogenic PD patients at greater risk of future cognitive impairment [ (59,107,(139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149); reviews: (27,150)]. Thus, genome-wide screens in PD subjects for variants that influence risk of severe OD or protect from developing OD may identify genetic factors that increase risk of, or offer protection from, cognitive impairment in PD.…”

Section: How Is Od Related To Disease Onset and Progression?mentioning

confidence: 99%

Olfactory Dysfunction in Familial and Sporadic Parkinson's Disease

Chase

Μarkopoulou

2020

Front. Neurol.

This minireview discusses our current understanding of the olfactory dysfunction that is frequently observed in sporadic and familial forms of Parkinson's disease and parkinsonian syndromes. We review the salient characteristics of olfactory dysfunction in these conditions, discussing its prevalence and characteristics, how neuronal processes and circuits are altered in Parkinson's disease, and what is assessed by clinically used measures of olfactory function. We highlight how studies of monogenic Parkinson's disease and investigations in ethnically diverse populations have contributed to understanding the mechanisms underlying olfactory dysfunction. Furthermore, we discuss how imaging and system-level approaches have been used to understand the pathogenesis of olfactory dysfunction. We discuss the challenging, remaining gaps in understanding the basis of olfactory dysfunction in neurodegeneration. We propose that insights could be obtained by following longitudinal cohorts with familial forms of Parkinson's disease using a combination of approaches: a multifaceted longitudinal assessment of olfactory function during disease progression is essential to identify not only how dysfunction arises, but also to address its relationship to motor and non-motor Parkinson's disease symptoms. An assessment of cohorts having monogenic forms of Parkinson's disease, available within the Genetic Epidemiology of Parkinson's Disease (GEoPD), as well as other international consortia, will have heuristic value in addressing the complexity of olfactory dysfunction in the context of the neurodegenerative process. This will inform our understanding of Parkinson's disease as a multisystem disorder and facilitate the more effective use of olfactory dysfunction assessment in identifying prodromal Parkinson's disease and understanding disease progression.

“…Kaempferol is potent in scavenging free radicals, thereby leading to the reduction in oxidative stress and protects the neurons. www.nature.com/scientificreports/ Olfactory dysfunction is very frequent in PD and has been reported in number of studies performed on PD patients [35][36][37] . Post-mortem studies performed on PD patients revealed that due to the formation of Lewy bodies in the olfactory bulb and in other regions of the brain such as the anterior olfactory nucleus, the piriform cortex, the amygdaldoid complex, the entortinal cortex and the hippocampal may lead to the olfactory dysfunction 38,39 .…”

Section: Discussionmentioning

confidence: 99%

Effect of kaempferol on the transgenic Drosophila model of Parkinson’s disease

Rahul

Naz

Jyoti

et al. 2020

Sci Rep

The present study was aimed to study the effect of kaempferol, on the transgenic Drosophila model of Parkinson's disease. Kaempferol was added in the diet at final concentration of 10, 20, 30 and 40 µM and the effect was studied on various cognitive and oxidative stress markers. The results of the study showed that kaempferol, delayed the loss of climbing ability as well as the activity of PD flies in a dose dependent manner compared to unexposed PD flies. A dose-dependent reduction in oxidative stress markers was also observed. Histopathological examination of fly brains using anti-tyrosine hydroxylase immunostaining has revealed a significant dose-dependent increase in the expression of tyrosine hydroxylase in PD flies exposed to kaempferol. Molecular docking results revealed that kaempferol binds to human alpha synuclein at specific sites that might results in the inhibition of alpha synuclein aggregation and prevents the formation of Lewy bodies.