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. Conventional therapy with calcium and vitamin D analogues does not restore calcium homeostasis and patients with chronic PS-HypoPT complain with several complications. From a neuropsychological standpoint, patients with PS-HypoPT present cognitive and affective symptoms: the more plausible pathophysiological mechanism resides in a direct effect of PTH in the central nervous system (CNS), but 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 15 PS-HypoPT rats and 15 healthy Sprague Dawley controls (WT) underwent biochemical testing (serum calcium) and behavioural testing namely Morris Water Maze MWM-to assess spatial learning and memory at 9 weeks of age.
Results: PS-HypoPT animals treated with standard calcium therapy and controls did not statistically differ in serum calcium levels (11.5±0.5 vs 11.2±0.2, P<0.001) and body weight (320±20 vs 335±20 gr). At MWM, during the training test PS-HypoPT animals displayed a significantly worse performance compared to controls, as suggested by a higher escape latency parameter (1° day 23.8±11.9 vs 14.6±9.3 sec,P=0.02; 2° day 13.3±11.6 vs 8.7±4.7 sec,P=0.02; 3° day 14.5±7.9 vs 11.01±8.4 secP=0.01). Both groups improved their results from the firs to the last day of training (escape latency PHPT 23.8±11.9 vs 9.2±4.5 sec P<0.001; WT 14.6±9.3 vs 5.5±0.6 sec P<0.001), even if PS-HypoPT group had a higher improvement compared to WT (multivariate analysisP=0.04). In the last day at the probe test, PS-HypoPT group and WT did not differ for the principal parameter escape latency and for secondary parameters, namely time in platform zone, entrance in the platform zone, total distance and platform crossings.
Conclusions: Animal model of HypoPT shows an impairment in spatial learning and memory compared to WT; training could ameliorate this condition. Further studies are ongoing evaluating other cognitive functions in such a model and could help to understand the physiopathological bases of neuropsychological symptom in patients with HypoPT.
21 May 2022 - 24 May 2022