Polysaccharides from Laminaria japonica protect memory abilities and neurogenesis in mice after cranial irradiation through ameliorating neuroinflammation and collagen IV degradation

Abstract

Background

Radiation-induced brain injury (RIBI) is one of the most common long-term complications for patients with malignant brain tumors after radiotherapy. At present, there is no effective treatment for RIBI. Recent studies have also confirmed that polysaccharides from laminaria japonica (LJP) display potential neuroprotective function. However, its mechanisms of neuroprotection remain unclear.

Aim

In this study, we aimed to explore the effect and underlying mechanism of LJP on neurogenesis in radiation-induced brain injury mice.

Methods

SPF two-month-old male mice were randomly divided into control group (Con), LJP treatment group (LJP), irradiation group (IR), and irradiation with LJP treatment group (IR + LJP). LJP (40 mg/kg/day) was intraperitoneally injected at one day before radiation for seven consecutive days (once daily). The mice were exposed to 10 Gy × 2 fractionated doses, once every other day, with a total dose of 20 Gy. Changes in cognitive function of mice following radiation were evaluated by the Morris water maze test. Furthermore, body weight and general status of mice were measured throughout the experiment. Immunohistochemical staining for neural proliferating cells (Ki67+ cells) and immature neurons (DCX + cells) was utilized to assay changes of neurogenesis in hippocampus. Microglial activation and collagen IV deposition within the neurogenic microenvironment were observed respectively by immunohistochemical staining for Iba-1 and Collagen IV in the hippocampus. Levels of pro-inflammatory cytokines (TNF-α and IL-1β) in the hippocampus were detected by ELISA kits post-radiation.

Results

Morris water maze test showed that LJP therapy markedly reduced the escape latency and increased the times of crossing platform and percent time of the target quadrant in the radiated mice. In addition, the decrease of the neural proliferating cells (Ki67+ cells) and immature neurons (DCX + cells) in the hippocampus of mice following irradiation was significantly mitigated by the LJP treatment, suggesting that LJP could prevent from neurogenesis damage after irradiation. LJP injection significantly attenuated degradation of collagen IV, activation of microglia, and increase of pro-inflammatory cytokines (TNF-α and IL-1β) levels in the neurogenic microenvironment of the hippocampus after radiation.

Conclusion

These findings suggest that LJP early treatment may mitigate radiation-induced cognitive impairments and that its mechanism may relate to its protection of neurogenesis by alleviating neuroinflammation and collagen IV degradation within the neurogenic microenvironment.

Keywords:

• Polysaccharides from laminaria japonica
• cognitive function
• neurogenesis
• microglia
• collagen IV
• radiation-induced brain injury

Author contributions

LW and WQL designed the study and supervised the project. SQZ, SYC, PA, and RC carried out the experiments. PA and RC collected and interpreted the experimental data. SQZ and SYC were significant contributors to drafting and revising the original manuscript. All authors read and approved the final manuscript.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by grants from the National Nature Science Foundation of China [81460479], the Natural Science Foundation of Guangxi Zhuang [2018GXNSFAA281299]

Notes on contributors

Siqin Zhang

Siqin Zhang, PhD student, at the College of Stomatology, Guangxi Medical University, Nanning, Guangxi, China. She is experienced in animal experiments.

Shaoyong Chen

Shaoyong Chen is a Master at the department of Dental Public Health, College of Stomatology, Guangxi Medical University, Nanning, Guangxi, China. He is experienced in data collection and analysis.

Pian Ao

Pian Ao is a Master student at the College of Stomatology, Guangxi Medical University, Nanning, China. She is experienced in histological experiments.

Rong Cai

Rong Chai is a Master student at the College of Stomatology, Guangxi Medical University, Nanning, Guangxi, China. She is experienced in establishing the irradiation-induced brain injury of animal model.

Wenqi Liu

Wenqi Liu, doctoral supervisor, MD, PhD, is a Professor/chief physician at the Head of the oncology Teaching and Research Section, Director of Radiotherapy Department of the Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. He is experienced in the Oncology radiology and directing the establishment of radiation models.

Li Wei

Li Wei, research supervisor, is a full Professor at the Department of Haman Anatomy, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China. He is experienced in designing the study and directing neuroanatomy.