Corsi P, Coyle J T
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1793-7. doi: 10.1073/pnas.88.5.1793.
The trisomy 16 (Ts16) mouse, which shares genetic and phenotypic homologies with Down syndrome, exhibits impaired development of the basal forebrain cholinergic system. Basal forebrains obtained from Ts16 and euploid littermate fetuses at 15 days of gestation were dissociated and cultured in completely defined medium, with cholinergic neurons identified by choline acetyltransferase (ChAT) immunoreactivity. The Ts16 cultures exhibited fewer ChAT-immunoreactive neurons, which were smaller and emitted shorter, smoother, and more simplified neurites than those from euploid littermates. Whereas the addition of beta-nerve growth factor (100 ng/ml) augmented the specific activity of ChAT and neuritic extension for both Ts16 and euploid cholinergic neurons, only Ts16 cultures exhibited an increase in the number and size of ChAT-immunoreactive neurons. Furthermore, Ts16 ChAT-immunoreactive neurites formed varicosities only in the presence of beta-nerve growth factor.
16三体（Ts16）小鼠与唐氏综合征存在遗传和表型同源性，其基底前脑胆碱能系统发育受损。在妊娠15天时，从Ts16和整倍体同窝胎儿获取基底前脑并解离，在完全限定培养基中培养，通过胆碱乙酰转移酶（ChAT）免疫反应性鉴定胆碱能神经元。Ts16培养物中ChAT免疫反应性神经元较少，这些神经元比整倍体同窝小鼠的神经元更小，发出的神经突更短、更平滑且更简单。虽然添加β-神经生长因子（100 ng/ml）可增强Ts16和整倍体胆碱能神经元的ChAT比活性和神经突延伸，但只有Ts16培养物中ChAT免疫反应性神经元的数量和大小有所增加。此外，只有在存在β-神经生长因子的情况下，Ts16 ChAT免疫反应性神经突才会形成膨体。
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