Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader-Willi syndrome

• Published in: Journal of neurodevelopmental disorders 2020-07, Vol.12 (1), p.21-21, Article 21
• Main Authors: Wu, Rui-Ni, Hung, Wei-Chen, Chen, Ching-Tsuey, Tsai, Li-Ping, Lai, Wen-Sung, Min, Ming-Yuan, Wong, Shi-Bing
• Format: Article
• Language: English
• Subjects: A-type potassium current; Adrenergic Neurons - metabolism; Analysis; Animal cognition; Animal models; Animals; Animals, Newborn; Apnea; Arousal; Brain slice preparation; Carbon dioxide; Central nervous system; Cognitive ability; Disease Models, Animal; Electrophysiology; Emotional behavior; Excitability; Experiments; Female; Firing pattern; Gene Expression Regulation, Developmental; Genetic disorders; Heterozygotes; Hypercapnia; Hypotonia; Intellectual disabilities; Locus coeruleus; Locus Coeruleus - metabolism; Mice; Necdin; Neonates; Nerve Tissue Proteins; Neurodevelopmental disorders; Neurons; Norepinephrine; Nuclear Proteins; Pathophysiology; Phenotypes; Potassium channels (voltage-gated); Potassium currents; Prader-Willi syndrome; Prader-Willi Syndrome - metabolism; Reflexes; Respiration
• ISSN: 1866-1947; 1866-1955
• DOI: 10.1186/s11689-020-09323-4

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS. Heterozygous necdin-deficient mice (B6.Cg-Ndn ) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/-p) animals, which were examined of LC-NE neuronal activity, developmental reflexes, and plethysmography. On slice electrophysiology, LC-NE neurons of Ndn mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndn mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia. LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis.