Osteoporosis and neurological impairment are associated with systemic oxidative stress in old rats.

TORRES ML; WANIONOK N; ANTONIO D. MCCARTHY; MOREL, GUSTAVO; FERNANDEZ JM

Congreso; LXIV Reunion Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LI Reunion Anual de la Sociedad de Farmacología Experimental (SAFE), XXI Reunion Anual de la Sociedad Argentina de Biología (SAB), XXXI Reunion Anual de la Sociedad Argentina de; 2020

Alzheimer´s disease (AD) is a neurodegenerative disorder that accounts for 50-75% cases of dementia in the elderly. It is characterized by high morbidity (mainly memory loss) and a scarcity of treatments to revert disease progression. As reported by Alzheimer's Disease International 2015 report, 46 million people worldwide suffer from this disease, with an estimated total cost of U$S 818 billion. Osteoporosis (OS) is defined as a decrease in bone density with compromised bone resistance and increased fracture risk. OS is a degenerative disorder that mainly affects the elderly, showing high morbidity and mortality due to osteoporotic fractures. Recent studies have found that there is an increase in the incidence of OS and hip fractures in patients with AD, compared to control (non-AD) individuals. On the other hand, it has been demonstrated that there is an increased prevalence of AD in women with OS. Thus, in ageing individuals there appears to be a bidirectional association between AD and OS. In this work, we have evaluated bone properties in two groups of 30-month-old Sprague Dawley rats with unimpaired (control) or impaired memory, assessed by NOR (Novel Object Recognition test). Histological and pQCT evaluation showed a decrease in bone quality of rats with impaired memory vs. control. Bone marrow progenitor cells (BMPC) were obtained from both groups, and their ex vivo ability to differentiate into osteoblasts was evaluated by PCR and phenotypic progression. We found that BMPC from rats with impaired memory have a lower capacity to differentiate into osteoblasts and a higher osteoclastogenic profile vs. control. Because both diseases have been related to oxidative stress, we also evaluated serum TBARS and conjugated dienes, and found these parameters to be elevated in rats with impaired memory vs. control. Our results suggest that oxidative stress could be a causal link between the decrease in bone quality and impaired memory observed in old individuals.