Stimulation of hippocampal neurogenesis by transcranial focused ultrasound and microbubbles in adult mice

Abstract

Transcranial focused ultrasound (FUS) and microbubble contrast agent, applied at parameters known to transiently increase blood-brain barrier permeability, were tested for the potential to stimulate hippocampal neurogenesis. In adult mice, FUS treatment significantly increased the number of proliferating cells and newborn neurons in the dentate gyrus of the dorsal hippocampus. This provides evidence that FUS with microbubbles can stimulate hippocampal neurogenesis, a process involved in learning and memory and affected in neurological disorders, such as Alzheimer's disease.

Keywords: Astrogenesis; Cell proliferation; Focused ultrasound; Hippocampus; Neurogenesis.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Figure 1

Hippocampal cell proliferation, neurogenesis and astrogenesis in adult mice 18 days following MRIgFUS treatment. Confocal z-stacks imaging the subgranular zone (SGZ) and granular cell layer (GCL) were acquired for both treated and untreated hemispheres (A) and utilized for analysis. Proliferating cells are labeled with BrdU (red), mature neurons with NeuN (blue) and astrocytes with S100β (green). From these images, the total number of BrdU-positive cells in the treated and untreated hemispheres were counted, extrapolated for the entire hippocampus and compared (B). Co-localization with the mature neuronal marker NeuN (C) and the astrocyte marker S100β (D) were determined, indicative of neurogenesis and astrogenesis, respectively. Overall, the proportion of hippocampal cell populations in the untreated and treated hemispheres (E) were examined to elucidate MRIgFUS effects on the hippocampus as a whole. Significant differences were defined as *p