Dettori Cristina, Ronca Francesca, Di Buono Giulia, Saba Alessandro, Di Lupo Francesca, Polini Beatrice, Ricardi Caterina, Frascarelli Sabina, Cetani Filomena, Marcocci Claudio, Zucchi Riccardo, Chiellini Grazia, Scalese Marco, Saponaro Federica
Department of Surgical, Medical and Molecular Pathology and Critical Care, 56126 Pisa, Italy.
Endocrine Unit, University Hospital of Pisa, 56124 Pisa, Italy.
J Pers Med. 2024 Feb 17;14(2):215. doi: 10.3390/jpm14020215.
Hypoparathyroidism (HypoPT) is characterized by hypocalcemia and undetectable/inappropriately low PTH. Post-surgical HypoPT (PS-HypoPT) is the most common cause. Patients with PS-HypoPT present neuropsychological symptoms, probably due to the PTH deprivation in the central nervous system (CNS). However, these mechanisms are still not elucidated. The aim of this study was to evaluate the effects of PTH deprivation on CNS in an animal model of PS-HypoPT via a cognitive/behavioral assessment approach.
A surgical rat model of PS-HypoPT was obtained and treated with calcium to maintain normocalcemia. Twenty PS-HypoPT rats and twenty sham-operated controls (Crl) underwent behavioral testing in a Morris Water Maze (MWM), Open Field (OF), and Elevated Plus Maze (EPM).
In the MWM, PTx rats showed a higher Escape Latency Time compared to Crl rats ( < 0.05); we observed a statistically significant improvement in the performance (day 1 to 8 < 0.001), which was less pronounced in PTx group. In the OF test, the time and distance spent in the zone of interest were significantly lower in the PTx group compared with the Crl ( < 0.01 and < 0.01). In the EPM experiment, the time spent in the close arm was significantly higher in the PTx group compared with the Crl ( < 0.01).
This animal model of PS-HypoPT shows an impairment in spatial memory, which improved after training, and a marked anxiety-like behavior, resembling the condition of patients with PS-HypoPT. Further studies are needed to elucidate mechanisms.
甲状旁腺功能减退症（HypoPT）的特征是低钙血症以及无法检测到/不适当的低甲状旁腺激素（PTH）水平。术后甲状旁腺功能减退症（PS-HypoPT）是最常见的病因。PS-HypoPT患者会出现神经心理症状，这可能是由于中枢神经系统（CNS）中PTH缺乏所致。然而，这些机制仍未阐明。本研究的目的是通过认知/行为评估方法，评估在PS-HypoPT动物模型中PTH缺乏对中枢神经系统的影响。
建立PS-HypoPT大鼠手术模型，并用钙进行治疗以维持血钙正常。20只PS-HypoPT大鼠和20只假手术对照组（Crl）在莫里斯水迷宫（MWM）、旷场试验（OF）和高架十字迷宫（EPM）中进行行为测试。
在MWM中，甲状旁腺切除（PTx）大鼠的逃避潜伏期比Crl大鼠更长（<0.05）；我们观察到其行为表现有统计学意义的改善（第1天至第8天<0.001），但PTx组的改善不太明显。在OF试验中，PTx组在感兴趣区域花费的时间和移动距离显著低于Crl组（<0.01和<0.01）。在EPM实验中，PTx组在封闭臂中花费的时间显著高于Crl组（<0.01）。
这种PS-HypoPT动物模型表现出空间记忆受损，训练后有所改善，以及明显的焦虑样行为，类似于PS-HypoPT患者的情况。需要进一步研究以阐明其机制。
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