Protective effects of low-intensity pulsed ultrasound on aluminum overload-induced cerebral damage through epigenetic regulation of brain-derived neurotrophic factor expression
Juan Li, Dong-dong Zhang, Chao-qing Wang, Miao Shi, Liang-liang Wang
Bioscience Reports 2019 · 10.1042/bsr20181185
Abstract
In consideration of its noninvasive administration and endogenous stimulation property, the enhancement of brain-derived neurotrophic factor (BDNF) via low-intensity pulsed ultrasound (LIPUS) could be a novel strategy for aluminum (Al) overload-induced cerebral damage. LIPUS was pre-treated 7 days before concomitantly given with aluminum chloride (AlCl 3 ) daily for a period of 42 days. Morris water maze and elevated plus maze were performed to analyze spatial learning and memory. Western Blot and immunoprecipitation were used to detect BDNF and histone acetylation of histone H3 lysine 9 (H3K9) and histone H4 lysine 12 (H4K12) in the hippocampus. Assay of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) indicated the extent of oxidative damages. Aluminium exposure in rats can cause attenuated spatial learning and memory, followed by up-regulated histone deacetylase 6 (HDAC6) expression, down-regulated H3K9 and H4K12 acetylation at the PIII and PIV promoter of BDNF, all of which will eventually inhibit BDNF expression. LIPUS can recover reduced cognitive function by restoring histone acetylation and BDNF expression, accompanied with increased SOD, GSH, and GSH-Px activity. LIPUS treatment might alleviate aluminium exposure-induced cognitive decline by acetylation regulation of BDNF expression and reducing oxidative stress in the hippocampus.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS, alone or with AlCl3
Target: other — “3.0 mm posterior and 2.5 mm lateral region of the bregma”
Device: Olympus / Panametrics · Panametrics, Waltham, MA, U.S.A. · A392S ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | ⚑ |
| Pulse duration (ms) | 50 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.528 | ✓✓✓ |
| 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 |
1 Hz, 5% duty cycle, 50 ms burst lengths; three sonications of 5 min with 5 min intervals, daily for 42 days (LIPUS-plus-AlCl3 rats started 7 days before AlCl3), under isoflurane.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Paper says 50 ms burst lengths; 5% duty cycle at 1 Hz is consistent with 50 ms, so burst was read as the pulse.exposures[0].fundamental_frequency_khz— Frequency not stated.exposures[0].target— Target not named; only coordinates relative to bregma given (hippocampus was the tissue analysed).n_subjects— Only group size (n=10 per group) given; 40 rats in four groups; two groups received LIPUS.exposures[0].unspecified_domain.ispta_w_cm2— 528 mW/cm2 converted to 0.528 W/cm2; measured by radiation force balance, domain not stated.n_sessions_per_subject— Daily for 42 days, with LIPUS-plus-AlCl3 rats pre-treated 7 days; total sessions not stated as a number.exposures[0].timing.sonication_duration_s— From 'three sonications, 5 min duration, and 5 min interval'.