Vitamin D3 supplementation may attenuate morphological and molecular abnormalities of the olfactory bulb in a mouse model of Down syndrome. (October 2022)

• Record Type: Journal Article
• Authors: Gomes, Fabiana de Campos; Santos, Isabella Boechat Faria; Stephani, Carolinne Makino; Ferrari, Merari de Fátima Ramires; Galvis-Alonso, Orfa Yineth; Goloni-Bertollo, Eny Maria; Melo-Neto, João Simão de; Pavarino, Érika Cristina
• Is Part Of: Tissue & cell. Volume 78(2022)
• Publication Date: 2022-10
• Subjects: Aβ amyloid-β -- AD Alzheimer disease -- APP beta-amyloid precursor protein -- DS Down syndrome -- EOAD early-onset Alzheimer's disease -- EPL external plexiform layer -- GCL granule cell layer -- GL Glomerular layer -- HE hematoxylin and eosin -- IPL internal plexiform layer -- MCL mitral cell layer -- MTHFR methylenetetrahydrofolate reductase -- NeuN neuronal nuclei -- PBS phosphate-buffered saline -- Pgp P-glycoprotein -- OB olfactory bulb -- VD Vitamin D -- VD3 Vitamin D3; Down syndrome -- Trisomic mice -- Vitamin D3 -- Olfactory bulb -- Amyloid beta; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2022.101898
• Languages: English
• ISSNs: 0040-8166

Abstract

Abstract: Individuals with Down syndrome (DS) exhibit impaired olfactory function and are at a higher risk of developing Alzheimer's disease (AD). Olfactory dysfunction may be an early clinical symptom of AD. Recent studies have demonstrated that vitamin D3 (VD3) exerts neuroprotective effects in mouse models of AD. In this study, we investigated the effects of VD3 on the morphology, immunolocalization, and markers involved in neuropathogenic processes, apoptosis, proliferation, cell survival, and clearance of amyloid peptides, along with neuronal markers in the olfactory bulb (OB) of an adult female mouse model of DS. Morphological and molecular analyses revealed that trisomic mice exhibited a volume reduction in the external plexiform layer, a decrease in the number of mitral and granule cells, and an increase in the expression of amyloid-β 42, caspase-3 p12, and P-glycoprotein. VD3 reversed certain morphological abnormalities in the OB of control trisomic mice (Ts(CO) ) and decreased the levels of caspase-3 p12 and methylenetetrahydrofolate reductase in the treated groups. The results demonstrated that trisomy factor causes morphofunctional abnormalities in the OB of Ts(CO) mice. Moreover, VD3 could represent a therapeutic target to attenuate morphological and molecular alterations in OB. Highlights: The morphological abnormalities in the olfactory bulb of trisomic mice are studied. High-dose vitamin D3 supplementation attenuates some morphological abnormalities. Attenuation of mitral and granular cell increase is observed. Expression levels of caspase-3 p12 and MTHFR are reduced, but not of Aβ42. Diffuse amyloid plaques were not observed.