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Heroin addiction and relapse-induced axonal transport impairment in the brain and detected by in vivo MRI
Yueyuan Luo1, Jun Yang2, Chengde Liao2, and Zhongping Zhang3
1Department of Radiology., The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China, 2Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China, 3Philips Healthcare China, Guangzhou, China

Synopsis

Heroin plays role in heroin-induced cognitive dysfunction is unclear. We used manganese-enhanced magnetic resonance imaging for to evaluate the effect of heroin on axon transport in the body.

Purpose

Drug addiction has become a considerable health problem due to the abuse drug and toxicity of the drug being abused and the resultant neuronal death and axon degeneration. Though it is a highly addictive drug, the effects of heroin on axonal transport function remain unclear. The aim of this study was to use magnetic resonance imaging (MRI) to characterize heroin addiction (HA)- and heroin-relapse (HR)-induced axon transport impairment and to explore the underlying mechanisms.

Methods

Heroin injections were administered to rats at different times and doses to establish HA and HR rodent models. Heroin-induced learning and memory dysfunction were evaluated by observing the rats in the Morris water maze. MRI was used to dynamically evaluate axonal transport from the olfactory pathway. The protein levels of ATPB, KIF5, COX IV and cytoplasmic dynein were assessed by western blot. TEM was used to observe ultrastructure changes. Neurofilament heavy chain (NF-H) protein levels were analyzed by immunofluorescence staining.

Result

HA model rats, and especially HR model rats, showed worse spatial learning and memory abilities than control rats. The escape latency of HR model rats was significantly increased, and the number of crossings and the stay time in the quadrant decreased significantly compared with that of HA model rats and control rats. The transport rate of Mn2+ in HA model rats was accelerated. HR model rats had a severely insufficient capacity for Mn2+ uptake and transport, and their axonal transport rate was significantly reduced compared to that of control rats (P<0.001). The levels of cytoplasmic dynein and KIF5 in rats in the HR group were significantly decreased (P<0.001), and the levels of energy-related proteins, including COX IV and ATPB, were lower than those in rats in the control group (P<0.001). The ultrastructure of the brains of heroin-exposed rats became abnormal, with neuronal apoptosis and mitochondrial disorders. Heroin-induced decreased expression of NF-Hs, and the staining intensity on the tissues from HA and HR model rats was significantly reduced (P<0.05).

Conclusion

Long-term relapse of heroin use can cause severe axonal transport disorders, which can be detected by MRI. The reduction in motor proteins and mitochondrial disorders may be the main reasons for this axonal transport damage. Thus, MRI is a potential tool for visualizing axon transport in individuals experiencing drug addiction, which also provides a new direction for the evaluation of addictive drug withdrawal.

Acknowledgements

No acknowledgement found.

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Figures

Mn2+ enhanced T1WI and quantification of signal intensity in AHE, HA and HR rats. Coronal T1W images of rats at 6 h (A) and 24 h (C) after MnCl2 injection. (B) The enhancement of Mn2+ in the OB and POT in AHE rats can be observed, and POT was higher in HA rats. In HR rats, a reduction in SI was observed in the OB. (D) SI in the OB, POT and DOT were higher in AHE rats, and that in the DOT and POT in HA rats increased. In HR rats, SI in the OB, POT and DOT was significantly lower. Data are represented as the mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, ns represents statistically no difference between the two groups.

The effect of heroin on the learning and memory abilities of rats in the MWM test.

The navigation test showed the escape latency of rats after heroin exposure was prolonged compared to control (B). The speed among all groups did not show difference (C). In the probe test, the swimming trajectory after evacuating the platform (A), the time spent in the target zone (D) and the number of crossings (E). Significant expression differences are represented as *P < 0.05, **P < 0.01, ***P < 0.001, in escape latency; # indicates the comparison between HR and HA rats; # # #P<0.001.


The expression levels of axonal motor proteins and energy metabolism proteins. (A) The protein expression levels of ATPB and cytoplasmic dynein were reduced in HA model rats. (B) ATPB, COX IV, cytoplasmic dynein and KIF5 protein levels were decreased in HR model rats. Each bar represents the mean±SEM (n=6), and significant expression differences are represented as *P < 0.05, **P < 0.01, ***P < 0.001.

Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)
2738
DOI: https://doi.org/10.58530/2022/2738