Magnesium diboride nanoparticles alleviate hippocampal neurons and synapses by upregulating BDNF to improve behavioral and brain structural abnormalities in diabetes mellitus mice complicated with depression

Zuo Xiaofei; Fan Huaju; Wu Qianying; Yin Hao; Chen Qichun; Zhang Huaxin; Pan Wenqing; Wang Yingshuai; Yang Nana

doi:10.16016/j.2097-0927.202604004

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Magnesium diboride nanoparticles alleviate hippocampal neurons and synapses by upregulating BDNF to improve behavioral and brain structural abnormalities in diabetes mellitus mice complicated with depression

Neuroscience | 更新时间：2026-09-16

- Magnesium diboride nanoparticles alleviate hippocampal neurons and synapses by upregulating BDNF to improve behavioral and brain structural abnormalities in diabetes mellitus mice complicated with depression
- Journal of Army Medical University Vol. 48, Issue 17, Pages: 2440-2452(2026)
- 作者机构：
  
  1.山东第二医科大学，生命科学与技术学院，山东潍坊
  2.山东第二医科大学，基础医学院，山东潍坊
  3.四川省第二退伍军人医院心理健康服务中心，四川成都
- 作者简介：
  
  Wang Yingshuai，E-mail： yingshuaiwang1987@163.com
  Yang Nana，E-mail： benben1980@126.com
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(81600360);the Key Project of Natural Science Foundation of Shandong Province(ZR2020KH008);the Joint Innovation and Development Project of Natural Science Foundation of Shandong Province(ZR2024LSW011);the Yuandu Scholar Foundation(000007060);the Horizontal Project Funded by Jiangsu Wukong Biotechnology Co., LTD(02191004)
- DOI：10.16016/j.2097-0927.202604004
  CLC： R587.2;R749.4;R914.3
- Received：01 April 2026，
  
  Revised：2026-07-30，
  
  Accepted：03 August 2026，
  
  Published：15 September 2026
- 稿件说明：
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左晓飞，范华菊，吴倩盈，等.硼化镁纳米颗粒通过上调BDNF减轻海马神经元及突触损伤改善糖尿病并发抑郁症小鼠行为和脑结构异常［J］.陆军军医大学学报，2026，48（17）：2440-2452.DOI：,10.16016/j.2097-0927.202604004.

Zuo X F，Fan H J，Wu Q Y，,et al.Magnesium diboride nanoparticles alleviate hippocampal neurons and synapses by upregulating BDNF to improve behavioral and brain structural abnormalities in diabetes mellitus mice complicated with depression［J］.J Army Med Univ，2026，48（17）：2440-2452.DOI：,10.16016/j.2097-0927.202604004.
左晓飞，范华菊，吴倩盈，等.硼化镁纳米颗粒通过上调BDNF减轻海马神经元及突触损伤改善糖尿病并发抑郁症小鼠行为和脑结构异常［J］.陆军军医大学学报，2026，48（17）：2440-2452.DOI：,10.16016/j.2097-0927.202604004. DOI：

Zuo X F，Fan H J，Wu Q Y，,et al.Magnesium diboride nanoparticles alleviate hippocampal neurons and synapses by upregulating BDNF to improve behavioral and brain structural abnormalities in diabetes mellitus mice complicated with depression［J］.J Army Med Univ，2026，48（17）：2440-2452.DOI：,10.16016/j.2097-0927.202604004. DOI：

摘要

目的

糖尿病并发抑郁症（diabetes mellitus complicated with depression，DD）是糖尿病患者常见的精神心理共病，表现为持续情绪低落以及糖代谢紊乱加重，严重影响疾病预后与患者生存质量。本研究通过构建DD小鼠模型，探讨硼化镁（MgB

）纳米颗粒对其行为和脑结构的影响。

方法

本研究利用扫描电子显微镜、X射线衍射对所制备的MgB

纳米颗粒进行表征，利用氢气微电极检测该纳米颗粒在体外以及体内胃、肠组织和血液中的释氢性能，通过动物实验评估其体内安全性。40只7~8周龄雄性C57BL/6J小鼠（体质量18~23 g）按照随机数字表法分为对照（Control）组、模型（DD）组、20 mg/kg MgB

组、30 mg/kg MgB

组和40 mg/kg MgB

组。DD组和3个不同剂量的MgB

组小鼠通过一次性腹腔注射链脲佐菌素（streptozotocin，STZ，150 mg/kg），在第5 d测空腹血糖（fasting blood glucose，FBG），若FBG≥11.3 mmol/L则持续喂养7 d，随后连续7 d腹腔注射脂多糖（lipopolysaccharide，LPS，0.5 mg/kg）来构建DD小鼠模型，Control组小鼠注射等剂量的柠檬酸-柠檬酸钠缓冲溶液。DD造模成功后，MgB

组小鼠连续灌胃对应剂量的MgB

纳米颗粒治疗7 d，其余组小鼠灌胃等体积的生理盐水。末次灌胃治疗24 h后通过行为学实验确定最佳治疗剂量。最佳MgB

纳米颗

粒剂量治疗后检测小鼠体质量、血清葡萄糖（glucose，GLU）含量；脑部MRI观察小鼠海马体体积、各向异性分数（fractional anisotropy，FA）和平均弥散系数（mean diffusivity，MD）；ELISA检测小鼠海马脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）；透射电子显微镜观察海马超微结构的变化。

结果

MgB

纳米颗粒在酸性条件下具有优异释氢特性，且释放过程均匀稳定。该材料兼具高储氢效能和安全性，可在胃内快速释放，在肠组织中缓慢释放，在血液中维持稳定。在旷场实验中，3个不同剂量的MgB

组小鼠在中央区域和外周区域的运动距离和穿格次数较DD组显著增加（

0.01）；在高架十字迷宫实验中，3个不同剂量的MgB

组小鼠在开放臂上的停留时间与运动距离较DD组显著增加（

0.05），在封闭臂上的停留时间显著降低、运动距离较DD组显著增加（

0.01）；在悬尾实验和强迫游泳实验中，3个不同剂量的MgB

组小鼠的不动时间较DD组显著缩短（

0.01）。以上行为学实验结果发现3种剂量的MgB

纳米颗粒组间疗效相当，因此选择20 mg/kg作为MgB

纳米颗粒的最佳治疗剂量。与DD组相比，MgB

纳米颗粒能够有效增加小鼠的体质量［（21.85±1.24）

（19.30±1.20）g，

0.01］、海马体积［（3.77±0.68）

（2.63±0.47）mm

，

0.01］、BDNF［（2 295.78±259.47）

（1 913.69±262.05）pg/mL，

0.05］和FA（左侧：0.23±0.03

0.16±0.02；右侧：0.22±0.04

0.15±0.02，

0.01），降低血清GLU含量［（25.97±4.66）

（38.25±8.42）mmol/L，

0.01］和MD［左侧：（5.11±0.09）×10

-4

（5.42±0.23）×10

-4

/s；右侧：（5.19±0.45）×10

-4

（5.60±0.27）×10

-4

/s，

0.05］，使得海马神经元核膜完整、核内染色质较均匀，细胞器较丰富，海马突触数量增加（5.33±1.22

3.56±1.50，

0.05），突触间隙增加［（21.66±2.72）

（17.23±2.69）nm，

0.01］，结构较为清晰。

结论

MgB

纳米颗粒通过上调BDNF水平，减少对海马神经元和突触的损伤，从而改善DD小鼠的行为和脑结构异常。

Abstract

Objective

Diabetes mellitus complicated with depression (DD) is a common psychiatric comorbidity in diabetic patients

characterized by persistent low mood and disordered glucose metabolism

which severely impacts di

sease prognosis and patient's quality of life. This study aims to investigate the effects of magnesium diboride (MgB

) nanoparticles on the behavior and brain structure of mice in a mouse model of DD.

Methods

Scanning electron microscopy and X-ray diffraction were performed to characterize the prepared MgB

nanoparticles

and hydrogen microelectrodes were employed to detect the hydrogen release properties of the nanoparticles

in vitro

and in the gastric

intestinal

and blood tissues in mice.

In vivo

safety was evaluated through animal experiments. Forty male C57BL/6J mice (7 to 8 weeks old

weighing 18 to 23 g) were randomly divided into a Control group

a model (DD) group

and 20

30 and 40 mg/kg MgB

groups. The mice in the DD group and the 3 MgB

groups were administered a single intraperitoneal injection of streptozotocin (STZ

150 mg/kg)

and fasting blood glucose (FBG) was measured on day 5. If FBG was ≥11.3 mmol/L

the mice were fed continuously for 7 d

followed by consecutive intraperitoneal injections of lipopolysaccharide (LPS

0.5 mg/kg) for 7 d to establish the DD mouse model

while the mice in the Control group were injected with an equal dose of citric acid-sodium citrate buffer. After successful DD modeling

the mice in the MgB

groups were intragastrically administered corresponding doses of MgB

nanoparticles for 7 consecutive days

while the mice in the other groups were given an equivalent volume of normal saline by gavage. Behavioral tests were performed 24 h after the final administration to determine the optimal therapeutic dose. Following treatment with the optimal dose of MgB

nanoparticles

body weight and serum glucose (GLU) levels were measured. Brain MRI scanning was performed to assess hippocampal volume

fractional anisotropy (FA) and mean diffusivity (MD). Hippocampal brain-derived neurotrophic factor (BDNF) levels were measured by ELISA. Ch

anges in hippocampal ultrastructure were observed by transmission electron microscopy.

Results

MgB

nanoparticles exhibited excellent hydrogen release properties under acidic conditions

with a uniform and stable release process. The nanoparticles possessed both high hydrogen storage capacity and safety

enabling rapid hydrogen release in the stomach

slow release in intestinal tissue

and stable maintenance in the blood. In the open field test

the mice in the 3 MgB

groups showed significant increases in the traveled distance and the crossing numbers in both the central and peripheral zones compared with the DD group (

0.01). In the elevated plus maze test

treatment of MgB

nanoparticles resulted in increased time spent and traveled distance on the open arms compared with those in the DD group (

0.05)

decreased time spent and more traveled distance in the closed arms compared with that in the DD group (

0.01). In the tail suspension and forced swim tests

the immobility time of mice in the 3 different MgB

dose groups was significantly shorter than that of the DD group (

0.01). These behavioral findings indicated comparable efficacy among the 3 MgB

nanoparticle doses; consequently

20 mg/kg was selected as the optimal therapeutic dose. Compared with the DD group

MgB

nanoparticles effectively increased body weight [(21.85±1.24)

(19.3±1.20) g

0.01

]

hippocampal volume [(3.77±0.68)

(2.63±0.47) mm

0.01

]

BDNF expression [(2 295.78±259.47)

(1 913.69±262.05) pg/mL

0.05

]

and FA (Left side: 0.23±0.03

0.16±0.02; right side: 0.22±0.04

0.15±0.02

0.01)

while reducing serum GLU levels [(25.97±4.66)

(38.25±8.42) mmol/L

0.01

]

and MD [Left side: (5.11±0.09)×10

-4

(5.42±0.23)×10

-4

/s; right side: (5.19±0.45)×10

-4

(5.60±0.27)×10

-4

0.05

]

. These improvements resulted in intact nuclear membranes in hippocampal neurons

relatively uniform intranuclear chromatin

abundant organelles

increased number of hippocampal synapses (5.33±1.22

3.56±1.50

0.05)

elevated synaptic cleft width [(21.66±2.72)

(17.23±2.69) nm

0.01

]

and clearer structural features.

Conclusion

MgB

nanoparticles improve behavioral and structural abnormalities in the brains of DD mice by upregulating BDNF levels and reducing damage to hippocampal neurons and synapses.

关键词

Keywords

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