Diabetes Induces Permanent Deleterious Effects in the Olfactory Bulb Associated with Increased Tyrosine Hydroxylase Expression and ERK1/2 Phosphorylation.

Diabetes mellitus type 2 (T2D) complications include brain damage which increases the risk of neurodegenerative diseases and dementia. An early manifestation of neurodegeneration is olfactory dysfunction (OD), which is also presented in diabetic patients. Previously, we demonstrated that OD correlates with IL-1ß and miR-146a overexpression in the olfactory bulb (OB) on a T2D rodent model, suggesting the participation of inflammation on OD. Here, we found that OD persists on a long-term T2D condition after the downregulation of IL-1ß. Remarkably, OD was associated with the increased expression of the dopaminergic neuronal marker tyrosine hydroxylase, ERK1/2 phosphorylation, and reduced neuronal activation on the OB of diabetic rats, suggesting the participation of the dopaminergic tone on the OD derived from T2D. Dopaminergic neurons are susceptible in neurodegenerative diseases such as Parkinson's disease; therefore further studies must be performed to completely elucidate the participation of these neurons and ERK1/2 signaling on olfactory impairment.

Protective effects of intracerebroventricular adiponectin against olfactory impairments in an amyloid ß1-42 rat model.

BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive impairment that eventually develops into dementia. Amyloid-beta (Aß) 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 Aß 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 Aß 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 (Aß1-42) rat model. Hence, we evaluated olfactory function by using a battery of olfactory tests aimed to assess olfactory memory, discrimination and detection in the Aß 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 Aß 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 Aß-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 Aß rats, which was prevented by the APN treatment. CONCLUSION: The present study describes the olfactory impairment of Aß treated rats and evidences the protective role that APN plays in the brain, by preventing the olfactory impairment induced by Aß1-42. These results may lead to APN-based pharmacological therapies aimed to ameliorate AD neurotoxic effects.