Scott Daniel S, Zaric Violeta, Tamminga Carol A, Butler Ryan K
Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Genes (Basel). 2025 Jul 24;16(8):863. doi: 10.3390/genes16080863.
BACKGROUND/OBJECTIVES: Prader-Willi Syndrome (PWS) is a neurodevelopmental disease associated with multiple behavioral features, including a prevalence for psychosis. The genetic causes of PWS are well characterized and involve the silencing or deletion of the paternal copy of a region of chromosome 15q11-13. One gene within this region, , a non-coding RNA, has been determined to have a determinant role in the manifestation of PWS. However, it remains unclear as to how the deletion of this allele can affect activity in the brain and influence psychosis-like behaviors.
In this study, we assessed the effects of the microdeletion of the paternal copy of on regional neural activity in psychosis-associated brain regions and psychosis-like behaviors in mice.
The results suggest that deletion causes increased c-Fos expression in the hippocampus and anterior cingulate cortex. deletion also results in behavioral phenotypes consistent with psychosis, most notably in stressful paradigms, with deficits in sensorimotor gating and augmented contextual as well as cued fear conditioning.
These results implicate the targets of in the presentation of a psychosis-like state with regional specificity.
背景/目的：普拉德-威利综合征（PWS）是一种神经发育疾病，与多种行为特征相关，包括精神病患病率。PWS的遗传病因已得到充分表征，涉及15号染色体q11 - 13区域父本拷贝的沉默或缺失。该区域内的一个基因，一种非编码RNA，已被确定在PWS的表现中起决定性作用。然而，尚不清楚该等位基因的缺失如何影响大脑活动并影响类似精神病的行为。
在本研究中，我们评估了父本拷贝的微缺失对与精神病相关的脑区区域神经活动以及小鼠类似精神病行为的影响。
结果表明，缺失导致海马体和前扣带回皮质中c-Fos表达增加。缺失还导致与精神病一致的行为表型，最明显的是在应激范式中，感觉运动门控缺陷以及情境性和线索性恐惧条件反射增强。
这些结果表明该基因的靶点在具有区域特异性的类似精神病状态的表现中起作用。
