Olfactory Dysfunction in Diabetic Rats is Associated with miR-146a Overexpression and Inflammation

Jiménez, Adriana; Organista‐Juárez, Diana; Torres-Castro, Areli; Guzmán-Ruiz, Mara; Estudillo, Enrique; Guevara‐Guzmán, Rosalinda

doi:10.1007/s11064-020-03041-y

Cited by 12 publications

(13 citation statements)

References 64 publications

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“…The social recognition test was performed as described previously [81][82][83]. Briefly, 2 days prior to the experiments and just before the test, adult rats were daily habituated to the testing cage (50 × 50 × 42 cm) for 4 min.…”

Section: Social Recognition Testmentioning

confidence: 99%

“…injection. The habituation/dishabituation test was performed using histological cartridges holding cotton swab scented with different extracts, corresponding to complex odors that have been previously reported for this test [81,83,84]. We only included the animals that were interested in exploring the water cartridges at the beginning of the test (VEH n = 8, APN n = 5, Aβ n = 7, APN-Aβ n = 5).…”

Section: Habituation-dishabituation Testmentioning

confidence: 99%

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Protective effects of intracerebroventricular adiponectin against olfactory impairments in an amyloid β1–42 rat model

et al. 2021

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Background Alzheimer’s disease (AD) is characterized by cognitive impairment that eventually develops into dementia. Amyloid-beta (Aβ) accumulation is a widely described hallmark in AD, and has been reported to cause olfactory dysfunction, a condition considered an early marker of the disease associated with injuries in the olfactory bulb (OB), the hippocampus (HIPP) and other odor-related cortexes. Adiponectin (APN) is an adipokine with neuroprotective effects. Studies have demonstrated that APN administration decreases Aβ neurotoxicity and Tau hyperphosphorylation in the HIPP, reducing cognitive impairment. However, there are no studies regarding the neuroprotective effects of APN in the olfactory dysfunction observed in the Aβ rat model. The aim of the present study is to determine whether the intracerebroventricular (i.c.v) administration of APN prevents the early olfactory dysfunction in an i.c.v Amyloid-beta1–42 (Aβ1–42) rat model. Hence, we evaluated olfactory function by using a battery of olfactory tests aimed to assess olfactory memory, discrimination and detection in the Aβ rat model treated with APN. In addition, we determined the number of cells expressing the neuronal nuclei (NeuN), as well as the number of microglial cells by using the ionized calcium-binding adapter molecule 1 (Iba-1) marker in the OB and, CA1, CA3, hilus and dentate gyrus (DG) in the HIPP. Finally, we determined Arginase-1 expression in both nuclei through Western blot. Results We observed that the i.c.v injection of Aβ decreased olfactory function, which was prevented by the i.c.v administration of APN. In accordance with the olfactory impairment observed in i.c.v Aβ-treated rats, we observed a decrease in NeuN expressing cells in the glomerular layer of the OB, which was also prevented with the i.c.v APN. Furthermore, we observed an increase of Iba-1 cells in CA1, and DG in the HIPP of the Aβ rats, which was prevented by the APN treatment. Conclusion The present study describes the olfactory impairment of Aβ treated rats and evidences the protective role that APN plays in the brain, by preventing the olfactory impairment induced by Aβ1–42. These results may lead to APN-based pharmacological therapies aimed to ameliorate AD neurotoxic effects.

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Section: Social Recognition Testmentioning

confidence: 99%

Section: Habituation-dishabituation Testmentioning

confidence: 99%

Protective effects of intracerebroventricular adiponectin against olfactory impairments in an amyloid β1–42 rat model

et al. 2021

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“…Activation of microglia was observed in the MOE of HFD-fed mice, and TNFα secreted by microglia can induce apoptosis in OSNs (reported in mice with olfactory deficits) . A recently published study has also shown an association between olfactory disfunction and IL-β-mediated inflammation and miR-146a overexpression in the MOB in the streptozotocin-induced T2D model . Nonetheless, the detailed role of neuroglia in dysregulation of olfactory processes in obesity/T2D is still not fully understood and warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Western Diet Accelerates the Impairment of Odor-Related Learning and Olfactory Memory in the Mouse

Lietzau

Nyström

Wang

et al. 2020

ACS Chem. Neurosci.

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Olfactory dysfunction could be an early indicator of cognitive decline in type 2 diabetes (T2D). However, whether obesity affects olfaction in people with T2D is unclear. This question needs to be addressed, because most people with T2D are obese. Importantly, whether different contributing factors leading to obesity (e.g., different components of diet or gain in weight) affect specific olfactory functions and underlying mechanisms is unknown. We examined whether two T2D-inducing obesogenic diets, one containing a high proportion of fat (HFD) and one with moderate fat and high sugar (Western diet, WD), affect odor detection/discrimination, odor-related learning, and olfactory memory in the mouse. We also investigated whether the diets impair adult neurogenesis, GABAergic interneurons, and neuroblasts in the olfactory system. Here, we further assessed olfactory cortex volume and cFos expression-based neuronal activity. The WD-fed mice showed declined odor-related learning and olfactory memory already after 3 months of diet intake ( p = 0.046), although both diets induced similar hyperglycemia and weight gain compared to those of standard diet-fed mice ( p = 0.0001 and p < 0.0001, respectively) at this time point. Eight months of HFD and WD diminished odor detection ( p = 0.016 and p = 0.045, respectively), odor-related learning ( p = 0.015 and p = 0.049, respectively), and olfactory memory. We observed no changes in the investigated cellular mechanisms. We show that the early deterioration of olfactory parameters related to learning and memory is associated with a high content of sugar in the diet rather than with hyperglycemia or weight gain. This finding could be exploited for understanding, and potentially preventing, cognitive decline/dementia in people with T2D. The mechanisms behind this finding remain to be elucidated.

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“…Recently, miRNA expression profiles in serum, plasma, and urine as well as various tissues particularly the pancreas, adipose tissue, and liver from patients with T2DM have been established which gives the accessibility to discover novel miRNA regulators in diabetes [62,64,115,116]. In addition, in most studies, microRNA showed to play a potential role in the severity and most diabetic complications associated with diabetes such as the inflammatory processes of atherosclerosis [117][118][119][120]. miR-342-5p, for example, has been reported to be linked with macrophage activation during atherosclerosis and cytokine secretion in CAD patients.…”

Section: Discussionmentioning

confidence: 99%

Expression of Circulating MicroRNAs and Myokines and Interactions with Serum Osteopontin in Type 2 Diabetic Patients with Moderate and Poor Glycemic Control: A Biochemical and Molecular Study

Al-Rawaf

Alghadir

Gabr

2021

BioMed Research International

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Background. Cellular miRNAs are expressed in tissue fluids with sufficient amounts and were identified as potential molecular targets for studying the physiological mechanisms and correlations with many human diseases particularly diabetes. However, molecular-based changes among older adults with diabetes mellitus (DM) are rarely fully elucidated. Aim. This study is aimed at identifying circulating miRNAs, which hold the potential to serve as biomarkers for the immune-inflammatory changes in older T2D patients with moderate and poor glycemic control status. In addition, the association of both myokines and osteopontin (OPN) levels with circulating miRNAs was identified. Methods. A total of 80 subjects aged 20–80 years were invited during the period of October 2017–May 2018 to participate in this descriptive cross-sectional study. All subjects were diagnosed with T2D for more than 5 years. Subjects were grouped based on glycemic control (HbA1c values) into two groups: moderate glycemic control (>7-8% HbA1c, no = 30 ) and poor glycemic control (>8% HbA1c, no = 50 ), respectively. Diabetic control parameters, fasting blood sugar (FS), HbA1c, fasting insulin (IF), insulin resistance (IR), HOMA-IR, inflammatory cytokines (IL-6, IL-8, IL-18, IL-23, TNF-α, and CRP), osteopontin, and myokines (adropin and irisin) were estimated by colorimetric and immune ELISA assays, respectively. In addition, real-time RT-PCR analysis was performed to evaluate the expression of circulating miRNAs, miR-146a and miR-144, in the serum of all diabetic subjects. Results. In this study, T2D patients with poor glycemic control showed a significant increase in the serum levels of IL-6, IL-8, IL-18, IL-23, TNF-α, CRP, and OPN and a reduction in the levels of myokines, adropin and irisin, compared to patients with moderate glycemic control. The results obtained are significantly correlated with the severity of diabetes measured by HbA1c, FS, IF, and HOMA-IR. In addition, baseline expression of miR-146a is significantly reduced and miR-144 is significantly increased in T2D patients with poor glycemic control compared to those with moderate glycemic control. In all diabetic groups, the expression of miR-146a and miR-144 is significantly correlated with diabetic controls, inflammatory cytokines, myokines, and serum levels of OPN. Respective of gender, women with T2D showed more significant change in the expressed miRNAs, inflammatory cytokines, OPN, and serum myokine markers compared to men. ROC analysis identified AUC cutoff values of miR-146a, miR-144, adropin, irisin, and OPN expression levels with considerable specificity and sensitivity which recommends the potential use of adropin, irisin, and OPN as diagnostic biomarkers for diabetes with varying glycemic control status. Conclusion. In this study, molecular expression of certain microRNA species, such as miR-146a and miR-144, was identified and significantly associated with parameters of disease severity, HbA1c, inflammatory cytokines, myokines, and serum osteopontin in T2D patients with moderate and poor glycemic control. The AUC cutoff values of circulating miRNAs, miR-146a and miR-144; myokines, adropin and irisin; and serum OPN were significantly identified by ROC analysis which additionally recommends the potential use of these biomarkers, miR-146a, miR-144, adropin, irisin, and OPN, as diagnostic biomarkers with considerable specificity and sensitivity for diabetes in patients with varying glycemic control status.

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Olfactory Dysfunction in Diabetic Rats is Associated with miR-146a Overexpression and Inflammation

Cited by 12 publications

References 64 publications

Protective effects of intracerebroventricular adiponectin against olfactory impairments in an amyloid β1–42 rat model

Protective effects of intracerebroventricular adiponectin against olfactory impairments in an amyloid β1–42 rat model

Western Diet Accelerates the Impairment of Odor-Related Learning and Olfactory Memory in the Mouse

Expression of Circulating MicroRNAs and Myokines and Interactions with Serum Osteopontin in Type 2 Diabetic Patients with Moderate and Poor Glycemic Control: A Biochemical and Molecular Study

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