Abstract
Scanning ultrasound (SUS) is a noninvasive approach that has recently been shown to ameliorate histopathological changes and restore memory functions in an Alzheimer's disease mouse model. Although no overt neuronal damage was reported, the short- and long-term effects of SUS on neuronal excitability and dendritic tree morphology had not been investigated. To address this, we performed patch-clamp recordings from hippocampal CA1 pyramidal neurons in wild-type mice 2 and 24 hours after a single SUS treatment, and one week and 3 months after six weekly SUS treatments, including sham treatments as controls. In both treatment regimes, no changes in CA1 neuronal excitability were observed in SUS-treated neurons when compared to sham-treated neurons at any time-point. For the multiple treatment groups, we also determined the dendritic morphology and spine densities of the neurons from which we had recorded. The apical trees of sham-treated neurons were reduced at the 3 month time-point when compared to one week; however, surprisingly, no longitudinal change was detected in the apical dendritic trees of SUS-treated neurons. In contrast, the length and complexity of the basal dendritic trees were not affected by SUS treatment at either time-point. The apical dendritic spine densities were reduced, independent of the treatment group, at 3 months compared to one week. Collectively, these data suggest that ultrasound can be employed to prevent an age-associated loss of dendritic structure without impairing neuronal excitability.
Highlights
Our group has reported that repeated scanning ultrasound (SUS) treatments reduced the amyloid plaque pathology in the APP23 transgenic mouse model of Alzheimer's disease (AD) and improved hippocampal-dependent spatial memory performance by activating brain-PLOS ONE | DOI:10.1371/journal.pone.0164278 October 11, 2016Ultrasound Treatment Maintains Dendritic Structure
In our analysis we focused on CA1 pyramidal neurons as this region and cell type has previously been reported to play an important role in hippocampal-dependent memory tasks [18, 19], the function of which was improved following SUS treatment in an amyloid-depositing mouse model of AD [1]
In the present study that had initially been designed as a safety study, we found no altered firing of CA1 pyramidal neurons after either a single SUS treatment or six repeated weekly doi:10.1371/journal.pone.0164278.g004
Summary
Our group has reported that repeated scanning ultrasound (SUS) treatments reduced the amyloid plaque pathology in the APP23 transgenic mouse model of Alzheimer's disease (AD) and improved hippocampal-dependent spatial memory performance by activating brain-. We evaluated the physiological effects of both a single and multiple SUS treatments on short- and long-term neuronal excitability, dendritic morphology and dendritic spine densities in the CA1 region of the hippocampus of wild-type mice (see Fig 1 for experimental design) This allowed us to determine the effect of different SUS treatments in a non-disease state system before eventually moving to a more complicated disease model, where alterations in neuronal function are already present at an early age. In our study using wild-type mice, we found that the different SUS treatment regimes had no deleterious effect on neuronal function or morphology In addition to this we made the interesting observation that repeated SUS treatments prevented reductions in the dendritic complexity and length of CA1 pyramidal neurons that occur in age-matched sham-treated wild-type mice over the course of three months, while a reduction in dendritic spine density was not halted. A more extensive follow-up study will determine, whether SUS treatments improves cognition in aging mice and what the underlying mechanism is of such an effect
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