Oligodendrocyte distribution in the Hippocampus

: Implications for Understanding Ultrasound-Enhanced Remyelination Mechanisms

Abstract

Demyelination is a feature of several neurodegenerative diseases including Alzheimer’s and Parkinsons disease. The regeneration of myelin, known as “remyelination” is possible, and one mediator of remyelination is neural activity. In neurodegenerative diseases, the loss of neural activity hinders remyelination. Transcranial focused ultrasound (TFUS) may have the potential to enhance remyelination. When pulses of ultrasound are delivered to brain tissue, it can stimulate neural activity with high spatial specificity. This project builds upon unpublished proteomics data indicating that in vitro exposure of acute rat hippocampal slices to 40 Hz ultrasound for 1 hour increased the expression of myelin basic protein (MBP) – a key component of myelin.

The first aim was to establish an acute model of demyelination in rat hippocampal slices using the demyelinating agent lysophosphatidylcholine (LPC). Demyelination was measured using immunoblots for MBP, and Oligodendrocyte transcription factor 2 (Olig2). Separate experiments investigated the effect of 1-hour of 40 Hz ultrasound on MBP and Olig2 expression by immunoblots in acute hippocampal slices. Finally, immunofluorescence was used to determine the distribution of oligodendrocytes and the mechanoreceptor Piezo1 in the hippocampus.

No differences in MBP or Olig2 were found using 10µM and 50µM LPC for 3 hours. No MBP expression changes were found following 1 hour of 40Hz ultrasound exposure in untreated hippocampal slices. Although Piezo1 was undetected, there were differences in oligodendrocyte distribution between hippocampal regions. The most densely populated area, the Stratum Lucidum was 1.7 times more populated than the least populated area, the Stratum Lacunosum-Moleculare.

Although we were unable to establish an acute model of demyelination to test the hypothesis that ultrasound stimulation enhances remyelination, the finding of a differential distribution of oligodendrocytes in hippocampus provides valuable insight into how ultrasound may differentially influence remyelination in these regions and lays the groundwork for future investigations in this field.

Date of Award	9 Oct 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Elek Molnar (Supervisor) & Daniel Whitcomb (Supervisor)