Endocrine Abstracts

Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disease which is characterized by hypocalcaemia and undetectable or inappropriately low serum parathyroid hormone (PTH). Post-surgical HypoPT (PS-HypoPT) is the most common cause, caused by accidental parathyroid removal/injury during neck surgery. From a neuropsychological standpoint, patients with PS-HypoPT present cognitive and neuropsychological symptoms: the more plausible pathophysiological mechanism resides in a direct effect of PTH in the central nervous system (CNS), since PTH Receptor 1 (PTHR1) and more abundantly PTH Receptor 2 (PTHR2) have been shown to be present in many areas of brain. However, these mechanisms are still not completely elucidated. The aim of this study was to evaluate the effects of PTH deprivation on CNS in an animal model (rat) of post-surgical hypoparathyroidism, by a cognitive/behavioural assessment approach.

Methods: A rat model (Sprague Dawley) of PS-HypoPT was obtained by the surgical removal of parathyroids at 5 weeks of age and treated with gluconate calcium 1% in drinking water to maintain normocalcemia. An experimental group of 20 PS-HypoPT rats and 20 healthy Sprague Dawley controls (WT) shamed operated, underwent biochemical testing (serum calcium) and behavioural testing namely Open Field and Elevated Plus Maze. Open Field (OF) provides information about locomotion and anxiety-related behaviours: when rats are placed into an open field, the higher is the “anxiety” level, the higher the proportion of time spent close to the wall. Elevated Plus Maze (EPM) assesses anxiety-related behaviours in rodents to explore open, unprotected spaces, compared to dark, enclosed spaces. The higher the “anxiety” levels, the lower the proportion of explorations in the open spaces in favour of the dark spaces.

Results: In OF test, the time and distance spent in the zone of interest (centre of arena) were significantly lower in the PTx group, compared with WT (P<0.01 and P<0.01). These data suggest a higher level of anxiety in PTx animals. In the EPM experiment the time spent in the close arm was significantly higher in the PTx group, compared with WT (P<0.01, Figure 6). This suggests a higher level of anxiety and stress in PTx group.

Conclusions: Animal model of PS-Hypo shows a higher level of anxiety and stress compared to controls. The model resembles the condition of patients with PS-Hypo. This condition could be related to the direct effect of PTH deprivation in brain in PSHypo. Further study are ongoing to highlight the molecular mechanisms.