The Effects of Transcranial Focused Ultrasound Stimulation of Nucleus Accumbens on Neuronal Gene Expression and Brain Tissue in High Alcohol-Preferring Rats
Erdem Deveci, Fahri Akbaş, Arif Şanlı Ergun, Ayse Kurtulmuş, Ali Barlas Koçak, Rabia Kevser Boyraz, Olgu Enis Tok, Mehmet Şerif Aydın, Özge Kılıç, Ayhan Bozkurt, Ömer Uysal, Mukaddes Eşrefoğlu, Abdurrahim Koçyiğit, Ahmet Öztürk, Andrew J. Lawrence, Ismet Kırpınar
Molecular Neurobiology 2023, 60, 1099-1116 · 10.1007/s12035-022-03130-9
Abstract
We investigated the effect of low-intensity focused ultrasound (LIFU) on gene expression related to alcohol dependence and histological effects on brain tissue. We also aimed at determining the miRNA-mRNA relationship and their pathways in alcohol dependence-induced expression changes after focused ultrasound therapy. We designed a case-control study for 100 days of observation to investigate differences in gene expression in the short-term stimulation group (STS) and long-term stimulation group (LTS) compared with the control sham group (SG). The study was performed in our Experimental Research Laboratory. 24 male high alcohol-preferring rats 63 to 79 days old, weighing 270 to 300 g, were included in the experiment. LTS received 50-day LIFU and STS received 10-day LIFU and 40-day sham stimulation, while the SG received 50-day sham stimulation. In miRNA expression analysis, it was found that LIFU caused gene expression differences in NAc. Significant differences were found between the groups for gene expression. Compared to the SG, the expression of 454 genes in the NAc region was changed in the STS while the expression of 382 genes was changed in the LTS. In the LTS, the expression of 32 genes was changed in total compared to STS. Our data suggest that LIFU targeted on NAc may assist in the treatment of alcohol dependence, especially in the long term possibly through altering gene expression. Our immunohistochemical studies verified that LIFU does not cause any tissue damage. These findings may lead to new studies in investigating the efficacy of LIFU for the treatment of alcohol dependence and also for other psychiatric disorders.
Abstract via europepmc.
Exposures
Exposure 1: LIFU to bilateral nucleus accumbens (NAc) in high alcohol-preferring rats
Target: nucleus accumbens — “nucleus accumbens (NAc), bilateral”
Device: IGT / Imasonic · Imasonic SAS, France · custom 10-element 1D array (2.4 MHz, dual simultaneous NAc targeting) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 2,400 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.002 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 250,000 | ✓✓✓⚑ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Isppa, domain unspecified (W/cm²) | 4.06 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.305 | ✓✓✓ |
Rats were anesthetized and received daily 30-min sessions (EG: 10 or 50 days depending on subgroup; sham group 50 days). Ultrasound parameters: PRF 250 kHz, duty cycle 50%, sonification duration 300 ms, delay 1700 ms, Isppa 4.06 W/cm2, Ispta 305 mW/cm2. STS received 10 days of real LIFU followed by 40 days of sham; LTS received 50 days of real LIFU; the sham group received 50 days of sham stimulation (kept in the device without stimulation).
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— PRF is stated as '250 kHz', an unusually high value for a pulse repetition frequency (typically Hz-range in tFUS protocols); recorded literally as stated rather than corrected, since the units cannot be verified from the text.n_sessions_per_subject— The two tFUS-exposed subgroups received different numbers of real-stimulation sessions (STS: 10 days; LTS: 50 days), so both values are recorded as a list rather than a single number.n_subjects— n_subjects (16) is the combined Experimental Group (STS+LTS) that received real LIFU stimulation at some point; the Sham Group (n=8) never received active stimulation and is excluded.