Irisin levels are correlated with age and behavioural performance in Post-surgical HypoPT condition

Federica Saponaro; Grazia Chiellini; Beatrice Polini; Caterina Ricardi; Patrizia Pignataro; Roberta Zerlotin; Angela Oranger; Silvia Colucci; Carlo Manuela Di; Graziana Colaianni; Alessandro Saba; Maria Grano

doi:10.1530/endoabs.99.RC2.2

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Endocrine Abstracts (2024) 99 RC2.2 | DOI: 10.1530/endoabs.99.RC2.2

ECE2024 Rapid Communications Rapid Communications 2: Calcium and Bone | Part I (6 abstracts)

Irisin levels are correlated with age and behavioural performance in Post-surgical HypoPT condition

Federica Saponaro ¹ , Grazia Chiellini ¹ , Beatrice Polini ¹ , Caterina Ricardi ¹ , Patrizia Pignataro ² , Roberta Zerlotin ³ , Angela Oranger ³ , Silvia Colucci ² , Manuela Di Carlo ³ , Graziana Colaianni ³ , Alessandro Saba ¹ & Maria Grano ³

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¹Biochemistry Unit, Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy; ²Department of Translational Biomedicine and Neuroscience, University of Bari, Bari, Italy; ³Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Bari, Italy

Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disease and Post-surgical HypoPT (PS-HypoPT) is the most common cause, caused by accidental parathyroid injury. From a neuropsychological standpoint, patients with PS-HypoPT present cognitive and neuropsychological symptoms. Irisin is a myokine secreted by contracting muscle, which mediates beneficial effects on several targets, including brain. The aim of this study was to evaluate irisin in the context of PS-HypoPT condition.

Methods: a surgical rat model of PS-HypoPT was obtained, treated with gluconate-calcium to maintain normocalcemia. A cohort of 40 animals was included, divided in 4 subgroups: n=10 PS-HypoPT rats (PTx) 11 weeks of age, n=10 PTx rats 28 weeks of age, n=10 controls shamed-operated (Crl) 11 weeks of age and n=10 Crl 28 weeks of age. All animals underwent serum calcium and irisin measurement and behavioural testing Morris Water Maze (MWM).

Results: Both PTx (n=20) and Crl rats (n=20) showed a normal growth and comparable serum calcium levels. In the whole animal cohort, serum irisin levels were statistically significantly lower in younger animals compared to elderly (16.5±3.3 vs 13.0±3.5, P=0.014), regardless the belonging group (PTx or Crl). In the ANOVA analysis including the 4 groups, we observed that PTx old animals (28 weeks of age) showed the lowest levels of irisin (P=0.04) and the rate of irisin decrease between 11 and 28 weeks of age was significantly higher in PTx animals, compared with Crl (P=0.03). We also observed that in MWM test, animals with lower levels of irisin (<14 mg/dl as median cut-off), showed a worse performance at the test, measured as parameters in the probe day (last day): number of entries in the zone of the platform (P=0.04), time spent in the zone of platform (P=0.03), total distance (P=0.02), resting time in the zone of platform (P=0.02). Moreover, PTx animals with lower levels of irisin, showed a higher Escape Latency Time compared to the other groups (P=0.01).

Conclusions: Irisin is a myokine, with potential protective effects on CNS. We observed that irisin is decreased with age and it is reduced in the animal model of PS-HypoPT. Moreover, irisin levels are correlated with the worse performance at behavioural testing evaluating locomotory capacity and memory in the PS-HypoPT group of animals. This mechanism could explain the known neuropsychological and cognitive symptoms of patients with PS-HypoPT. Further studies are ongoing to understand the role of irisin and its downstream effectors on CNS in PS-HypoPT.