Dendritic Spine Abnormalities in Hippocampal CA1 Pyramidal Neurons Underlying Memory Deficits in the SAMP8 Mouse Model of Alzheimer's Disease

Abstract

Abstract. SAMP8 is a strain of mice with accelerated senescence. These mice have recently been the focus of attention as they show several alterations that have also been described in Alzheimer's disease (AD) patients. The number of dendritic spines, spine plasticity, and morphology are basic to memory formation. In AD, the density of dendritic spines is severely decreased. We studied memory alterations using the object recognition test. We measured levels of synaptophysin as a marker of neurotransmission and used Golgi staining to quantify and characterize the number and morphology of dendritic spines in SAMP8 mice and in SAMR1 as control animals. While there were no memory differences at 3 months of age, the memory of both 6-and 9-month-old SAMP8 mice was impaired in comparison with age-matched SAMR1 mice or young SAMP8 mice. In addition, synaptophysin levels were not altered in young SAMP8 animals, but SAMP8 aged 6 and 9 months had less synaptophysin than SAMR1 controls and also less than 3-month-old SAMP8 mice. Moreover, while spine density remained stable with age in SAMR1 mice, the number of spines started to decrease in SAMP8 animals at 6 months, only to get worse at 9 months. Our results show that from 6 months onwards SAMP8 mice show impaired memory. This age coincides with that at which the levels of synaptophysin and spine density decrease. Thus, we conclude that together with other studies that describe several alterations at similar ages, SAMP8 mice are a very suitable model for studying AD.

Senescence-Accelerated Mice P8: A Tool to Study Brain Aging and Alzheimer's Disease in a Mouse Model

“…Furthermore, several studies have characterized alterations in the dendritic spine density in mouse models of AD, including a significant decrease in dendritic spine density in the hippocampus of the J20 and APP/PS1 mice [83] and in the CA1 subzone in Tg2576 and APP/Lo mice [84]. Dendritic spine state alterations have been described in SAMP8 [70].…”

“…Del Valle et al [70] demonstrated altered synaptic dendrite distribution and number in SAMP8 compared with SAMR1. This suggests that the learning capabilities of SAMP8 decrease, since thin spines have been related with information acquisition (learning) [108][109][110].…”

“…Furthermore, SAMP8 has been considered to be a sound model for investigating the pathophysiology of the early events in AD, due to Aβ accumulation [69,70], cerebral amyloid angiopathy [71], brain blood barrier alterations [71][72][73], and different hippocampal protein aggregates [74].…”

Application of APP/PS1 Transgenic Mouse Model for Alzheimer’s Disease

“…Synapses loss, especially dendritic spines loss which manifests as morphological changes is closely correlated with cognitive impairment [59]. The decrease of synaptic efficacy in the hippocampus is much earlier than the appearance of neuron degeneration [60]. Previous work has reported that the loss of synapses in the dendritic spines and dendrites was the main reason for the decrease of the synapse in APP/PS1 Tg mice [61].…”

Recent Progress of the Golgi Technique and Electron Microscopy To Examine Dendritic Pathology In Alzheimer‘s Disease

“…In an experimental study on mice with accelerated senescence, the use of Golgi staining revealed that the dendritic spines started to decrease as the age of the animals advanced and their memory declined [16].…”