Hans-Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Integrated Research and Treatment Center-Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
Elife. 2017 Nov 14;6:e28685. doi: 10.7554/eLife.28685.
Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used knockout ( mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.
神经元蜡样脂褐质沉积症（JNCL 或巴滕病）是由 基因突变引起的，是儿童期最常见的遗传性神经退行性疾病，导致广泛的中枢神经系统功能障碍和过早死亡。 突变对疾病进展、神经元传递以及中枢神经网络功能障碍的影响知之甚少。我们使用 基因敲除（ 小鼠，并发现焦虑相关行为增加，厌恶学习受损，运动功能明显受到影响，包括协调障碍。膜片钳和松散膜片记录显示杏仁核、海马和小脑网络中的抑制性和兴奋性突触传递受到严重影响。突触前释放特性的变化可能是由于 CLN3 蛋白功能障碍。此外，中枢网络中钙结合蛋白、神经肽 Y、parvalbumin 和 GAD65 阳性中间神经元的丧失共同支持 GABA 能中间神经元退化可能是中枢 GABA 能抑制丧失的原因的假说。
