Olfaction deterioration in cognitive disorders in the elderly

Ottaviano, Giancarlo; Frasson, Giuliana; Nardello, Ennio; Martini, Alessandro

doi:10.1007/s40520-015-0380-x

Cited by 51 publications

(38 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Overall, our findings suggest the recognition of a potential time point from our work with the olfactory bulb and the idea that loss of olfaction is an early-enough marker in neurodegeneration to recognize that the initiation of strategies which will overcome a continuing loss of cognitive abilities will need to be considered and implemented [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Changes in Vascular and Immune Cell Content of an LPS Treated Rat Olfactory Bulb PD Model, Measured by Fluorescence Deconvolution Microscopy

Bick¹,

Poindexter²,

Doursout³

2017

J Cytokine Biol

View full text Add to dashboard Cite

Objective: We have previously shown changes in protein, immune cell, nitric oxide a neurotrophic factor content and distribution in the olfactory bulb of an endotoxin-treated rat model, as all these factors have been shown to be involved in neurodegeneration. We expanded our studies by fluorescently imaging smooth muscle actin and endothelial nitric oxide synthase (eNOS), both markers of blood vessels, to investigate loss of vasculature content, as well as imaging locations and quantities of immune cells. The work was performed to shed further light on associations between vessel integrity and immune cell initiated endothelial disruption. Our goal was to demonstrate that cytokine production, NOS induction and immune cell increases, are likely part of the process that leads to a loss of olfaction and dopaminergic signaling and includes vascular perturbations.Methods: Rats were sacrificed following lipopolysaccharide (LPS) treatment. Olfactory bulbs were harvested, sectioned from top to bottom to include the tract and sensory neurons, and probed for markers of inflammation. Inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), eNOS, interleukin-1 beta (IL-1β), TNF-α, interleukin-6, glial cell derived neurotrophic factor (GDNF) and circulating nitric oxide (NO) were imaged together with tagged macrophages, T-cells, B-cells and neutrophils.Results: Serum NO levels indicated that an inflammatory episode had occurred, being significantly higher in treated animals, with tissue levels of NOS elevated for an extended period of time. Immune cell clusters were seen in a number of areas and the localization of NOS isomers suggests that they have divergent roles in neurodegeneration. For instance, eNOS was associated with blood vessels, iNOS with glial and matrix cells and nNOS with glial cells and neurons. T and B-cell numbers showed a sustained increase; neutrophil numbers rapidly increased then returned to baseline levels; macrophage numbers increased and remained high; LAMP positive cell numbers (NK-cells) increased and remained high; GDNF content increased; IL-6, TNF-α and IL-1β levels all rapidly increased, before dropping to untreated levels, while circulating, NO levels increased dramatically. Of interest, the images of vascular content, immune cell content, eNOS and smooth muscle actin, allowed us to show detrimental interactions between cells, factors and vessels. Our data show that the majority of the vessels were intact, though sections of interest were 'extracted' to reveal possible leaky areas. Specific sites of IL-6 positive lymphocyte clustering were noted around vessels, suggesting that interactions are occurring that lead to disruptions of blood vessel tunicae, allowing the internalization of circulating cells and subsequent cytokine-initiated endothelial cell death. Conclusion:Our findings suggest that protective GDNF and eNOS, which maintains vascular tone, are possibly synthesized too late to combat cytokine initiated neuron damage, glial activation and chronic loss of va...

show abstract

Section: Discussionmentioning

confidence: 99%

Changes in Vascular and Immune Cell Content of an LPS Treated Rat Olfactory Bulb PD Model, Measured by Fluorescence Deconvolution Microscopy

Bick¹,

Poindexter²,

Doursout³

2017

J Cytokine Biol

View full text Add to dashboard Cite

show abstract

“…Where a patient complains of reduced or dysfunctional taste, often they are in fact suffering from olfactory impairment and describing consequent impact on flavour perception (95) (178) . Where a patient has previously been treated with corticosteroids with improvement in smell, it is likely that they are suffering from sinonasal disease.…”

Section: Idiopathic Olfactory Dysfunctionmentioning

confidence: 99%

Position paper on olfactory dysfunction

Hummel¹,

Whitcroft²,

Andrews³

et al. 2017

Rhin

123

112

View full text Add to dashboard Cite

show abstract

“…Exposure to air pollution, particularly fine particulate matter (PM2.5), also leads to reduced sense of smell and anosmia (Ajmani et al, 2016a;Ajmani et al, 2016b) and can damage nasal tissue (Calderon-Garciduenas et al, 2003). Interestingly, anosmia and a decline of sense of smell precede the onset of neurodegenerative disorders (Doty, 1989;Wilson et al, 2009;Rahayel et al, 2012;Growdon et al, 2015;Ottaviano et al, 2016;Roberts et al, 2016;Murphy, 2019) and is also associated with depressive disorders (Croy et al, 2014;Kohli et al, 2016). Similar damage and sensory deficits have been implicated in COVID-19 pathology (Cooper et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Intranasal Administration of Functionalized Soot Particles Disrupts Olfactory Sensory Neuron Progenitor Cells in the Neuroepithelium

Norwood

Gharpure

Kumal

et al. 2020

Preprint

View full text Add to dashboard Cite

Exposure to air pollution has been linked to the development of neurodegenerative diseases and anosmia, but the underlying mechanism is not known. Additionally, the loss of olfactory function often precedes the onset of neurodegenerative diseases. Chemical ablation of olfactory sensory neurons blocks the drainage of cerebrospinal fluid (CSF) through the cribriform plate and alters normal CSF production and/or circulation. Damage to this drainage pathway could contribute to the development of neurodegenerative diseases and could link olfactory sensory neuron health and neurodegeneration. Here, we investigated the impact of intranasal treatment of combustion products (laboratory-generated soots) and their oxygen functionalized derivatives on mouse olfactory sensory neurons, olfactory nerve cell progenitors, and the behavior of the mouse. We found that after a month of every-other-day intranasal treatment of soots, there was minimal effect on olfactory sensory neuron anatomy or exploratory behavior in the mouse. However, oxygen-functionalized soot caused a large decrease in globose basal cells, which are olfactory progenitor cells. These results suggest that exposure to air pollution damages the olfactory neuron progenitor cells, and could lead to decreases in the number of olfactory neurons, potentially disrupting CSF drainage.

show abstract

Olfaction deterioration in cognitive disorders in the elderly

Cited by 51 publications

References 84 publications

Changes in Vascular and Immune Cell Content of an LPS Treated Rat Olfactory Bulb PD Model, Measured by Fluorescence Deconvolution Microscopy

Changes in Vascular and Immune Cell Content of an LPS Treated Rat Olfactory Bulb PD Model, Measured by Fluorescence Deconvolution Microscopy

Position paper on olfactory dysfunction

Intranasal Administration of Functionalized Soot Particles Disrupts Olfactory Sensory Neuron Progenitor Cells in the Neuroepithelium

Contact Info

Product

Resources

About