Potential Use of Exfoliated and Cultured Olfactory Neuronal Precursors for In Vivo Alzheimer’s Disease Diagnosis: A Pilot Study

Riquelme, Agustín; Valdés-Tovar, Marcela; Ugalde, Oscar; Maya-Ampudia, Vanessa; Fernández, M Puig; Mendoza-Durán, Leticia; Rodríguez-Cárdenas, Leslye; Benítez‐King, Gloria

doi:10.1007/s10571-019-00718-z

Cited by 8 publications

(8 citation statements)

References 63 publications

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“…Moreover, in postmortem samples obtained from Alzheimer's disease patients, paired helical filaments of tau protein and amyloid-β plaques similar to those found in cortical and subcortical neurons have been described in olfactory neuroepithelial cells characterized by cytokeratin-18 expression reflecting its stromal epithelial cell nature, as well as in olfactory neurons characterized by III β-tubulin expression [60,61]. Recently, neuronal precursors were obtained from alive patients with Alzheimer's disease diagnosis and demonstrated the paired helical filaments, as well as increased levels of tau total and phospho-tau supporting that olfactory neuroepithelial cells are a mirror model that reflects molecular changes produced in the CNS and useful to study different stages of neurodevelopment in samples obtained from alive patients [62].…”

Section: Melatonin Stimulatory Effects On Structural Neuroplasticity ...mentioning

confidence: 94%

Circadian Modulation of Neurodevelopment in the Adult Human Brain: Importance of Melatonin

Solís‐Chagoyán¹,

Muñóz-Delgado²,

Estrada-Reyes³

et al. 2022

Circadian Rhythm - New Insights Into Physiological and Pathological Implications

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Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine synthesized by the pineal gland in the dark phase of the photoperiod. Released melatonin into the pineal recess and the cerebrospinal fluid is the chemical signal that conveys information about the environmental illumination to the brain. In recent years, it was described that melatonin stimulates the neurodevelopment in the adult brain. During this complex process, new neurons are formed and differentiate to form synaptic connections. Neuropsychiatric disorders are characterized by the loss of neuronal connectivity and diminished levels of melatonin, among other features. Importantly, these patients have impaired circadian rhythms. In recent years, evidence aroused indicating that neurodevelopment occurs in the adult brain, making important the study of chemical compounds and endogenous molecules that stimulate neurodevelopment to reestablish synaptic connectivity. In this chapter, we will review the evidence that supports the circadian melatonin modulatory effects on neurodevelopment and its importance for the treatment of neuropsychiatric diseases.

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Section: Melatonin Stimulatory Effects On Structural Neuroplasticity ...mentioning

confidence: 94%

Circadian Modulation of Neurodevelopment in the Adult Human Brain: Importance of Melatonin

Solís‐Chagoyán¹,

Muñóz-Delgado²,

Estrada-Reyes³

et al. 2022

Circadian Rhythm - New Insights Into Physiological and Pathological Implications

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“…Furthermore, purified cultures obtained by cloning selection through limiting dilution significantly increases cell viability at least until passage 60 [50]. In this work, we will refer to neural stem cells isolated from the olfactory neuroepithelium as olfactory neuronal precursors (ONPs), similar to [8,9,50,51].…”

Section: Olfactory Neuroepithelium and The Non-invasive Isolation Of Onpsmentioning

confidence: 99%

“…This limitation potentially leads to wrong conclusions about the pathogenic mechanisms and ultimately may dampen the development of effective therapies. Alternatively, patient-derived cells of neuronal lineage such as those from the olfactory epithelium may provide a convenient solution to this problem [5,9,42]. On the other hand, the accumulation of superoxide anion increases the levels of compounds such as 4-hydroxynonenal (4-HNE).…”

Section: Alzheimer's Disease-related Oxidative Stress In the Olfactory Epithelium And Onpsmentioning

confidence: 99%

“…Alternatively, the culture of olfactory neuronal precursors (ONPs) has emerged as a relatively simpler tool to study different brain disorders, taking advantage of their neuronal lineage and their readily non-invasive isolation [7,8]. For instance, patient-derived ONPs manifest abnormal amyloid components together with tau hyperphosphorylation, which have recently led to the proposal of these cells as a novel diagnostic tool for AD [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease

Gómez-Virgilio

Luarte

Ponce

et al. 2021

IJMS

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Among all the proposed pathogenic mechanisms to understand the etiology of Alzheimer’s disease (AD), increased oxidative stress seems to be a robust and early disease feature where many of those hypotheses converge. However, despite the significant lines of evidence accumulated, an effective diagnosis and treatment of AD are not yet available. This limitation might be partially explained by the use of cellular and animal models that recapitulate partial aspects of the disease and do not account for the particular biology of patients. As such, cultures of patient-derived cells of peripheral origin may provide a convenient solution for this problem. Peripheral cells of neuronal lineage such as olfactory neuronal precursors (ONPs) can be easily cultured through non-invasive isolation, reproducing AD-related oxidative stress. Interestingly, the autofluorescence of key metabolic cofactors such as reduced nicotinamide adenine dinucleotide (NADH) can be highly correlated with the oxidative state and antioxidant capacity of cells in a non-destructive and label-free manner. In particular, imaging NADH through fluorescence lifetime imaging microscopy (FLIM) has greatly improved the sensitivity in detecting oxidative shifts with minimal intervention to cell physiology. Here, we discuss the translational potential of analyzing patient-derived ONPs non-invasively isolated through NADH FLIM to reveal AD-related oxidative stress. We believe this approach may potentially accelerate the discovery of effective antioxidant therapies and contribute to early diagnosis and personalized monitoring of this devastating disease.

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“…Pharmacological responses also have been studied in these cells to validate drug responses for the treatment of Parkinson’s disease [ 13 ]. Neuronal precursors derived from this tissue and cultured in selective media [ 14 , 15 ] been used to characterize schizophrenia, bipolar disorder and Alzheimer’s disease biomarkers [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors

et al. 2022

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Melatonin (MEL), an indolamine with diverse functions in the brain, has been shown to produce antidepressant-like effects, presumably through stimulating neurogenesis. We recently showed that the combination of MEL with ketamine (KET), an NMDA receptor antagonist, has robust antidepressant-like effects in mice, at doses that, by themselves, are non-effective and have no adverse effects. Here, we show that the KET/MEL combination increases neurogenesis in a clone derived from human olfactory neuronal precursors, a translational pre-clinical model for effects in the human CNS. Neurogenesis was assessed by the formation of cell clusters > 50 µm in diameter, positively stained for nestin, doublecortin, BrdU and Ki67, markers of progenitor cells, neurogenesis, and proliferation. FGF, EGF and BDNF growth factors increased the number of cell clusters in cultured, cloned ONPs. Similarly, KET or MEL increased the number of clusters in a dose-dependent manner. The KET/MEL combination further increased the formation of clusters, with a maximal effect obtained after a triple administration schedule. Our results show that the combination of KET/MEL, at subeffective doses that do not produce adverse effects, stimulate neurogenesis in human neuronal precursors. Moreover, the mechanism by which the combination elicits neurogenesis is meditated by melatonin receptors, CaM Kinase II and CaM antagonism. This could have clinical advantages for the fast treatment of depression.

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Potential Use of Exfoliated and Cultured Olfactory Neuronal Precursors for In Vivo Alzheimer’s Disease Diagnosis: A Pilot Study

Cited by 8 publications

References 63 publications

Circadian Modulation of Neurodevelopment in the Adult Human Brain: Importance of Melatonin

Circadian Modulation of Neurodevelopment in the Adult Human Brain: Importance of Melatonin

Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease

Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors

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