Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.
Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Chile.
J Alzheimers Dis. 2021;82(s1):S5-S18. doi: 10.3233/JAD-201195.
Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. This neurodegenerative syndrome affects cognition, memory, behavior, and the visual system, particularly the retina.
This work aims to determine whether the 5xFAD mouse, a transgenic model of AD, displays changes in the function of retinal ganglion cells (RGCs) and if those alterations are correlated with changes in the expression of glutamate and gamma-aminobutyric acid (GABA) neurotransmitters.
In young (2-3-month-old) and adult (6-7-month-old) 5xFAD and WT mice, we have studied the physiological response, firing rate, and burst of RGCs to various types of visual stimuli using a multielectrode array system.
The firing rate and burst response in 5xFAD RGCs showed hyperactivity at the early stage of AD in young mice, whereas hypoactivity was seen at the later stage of AD in adults. The physiological alterations observed in 5xFAD correlate well with an increase in the expression of glutamate in the ganglion cell layer in young and adults. GABA staining increased in the inner nuclear and plexiform layer, which was more pronounced in the adult than the young 5xFAD retina, altering the excitation/inhibition balance, which could explain the observed early hyperactivity and later hypoactivity in RGC physiology.
These findings indicate functional changes may be caused by neurochemical alterations of the retina starting at an early stage of the AD disease.
阿尔茨海默病（AD）是全球最常见的痴呆症形式。这种神经退行性综合征影响认知、记忆、行为和视觉系统，特别是视网膜。
本研究旨在确定 AD 的转基因模型 5xFAD 小鼠是否表现出视网膜神经节细胞（RGC）功能的变化，以及这些变化是否与谷氨酸和γ-氨基丁酸（GABA）神经递质表达的变化相关。
在年轻（2-3 月龄）和成年（6-7 月龄）5xFAD 和 WT 小鼠中，我们使用多电极阵列系统研究了各种类型视觉刺激对 RGC 的生理反应、放电率和爆发。
在年轻小鼠的 AD 早期，5xFAD RGC 的放电率和爆发反应表现出过度活跃，而在成年 AD 晚期则表现出活动不足。在年轻和成年 5xFAD 中观察到的生理变化与节细胞层中谷氨酸表达的增加密切相关。GABA 染色在内核和神经纤维层增加，在成年 5xFAD 视网膜中比在年轻 5xFAD 中更为明显，改变了兴奋/抑制平衡，这可以解释 RGC 生理中观察到的早期过度活跃和后期活动不足。
这些发现表明，功能变化可能是由 AD 疾病早期视网膜的神经化学改变引起的。
