1型糖尿病大鼠皮质神经元与突触数量变化对认知功能的影响

doi:10.3969/j.issn.1006-5725.2025.13.008

Abstract

Abstract:

Objective To explore the alterations in the numbers of cortical neurons and synapses in type 1 diabetic rats and their correlation with cognitive dysfunction. Methods A type 1 diabetes model was induced by intraperitoneal injection of streptozotocin （STZ）. Four-month-old specific pathogen-free （SPF）-grade Sprague-Dawley （SD） rats were randomly allocated into a control group and a diabetic group， with five rats in each group. After three months of continuous feeding， optical fractionator stereology was employed to quantitatively analyze the volume of the cerebral cortex， the number of neurons， and the number of synapses. Results In comparison with the control group， the volume of the cerebral cortex in the diabetic group decreased by 6.00%， and the number of neurons decreased by 14.09%. However， these differences were not statistically significant （P > 0.05）. Never theless， the density of synapses significantly decreased by 70.14% （P < 0.05）， and there was a significant difference in the number of Spinophilin/Neurabin-positive synaptic boutons per neuron in the cortex （P < 0.05）. Conclusion Although early-stage type 1 diabetes does not lead to a significant loss of cortical neurons， the substantial reduction in synaptic numbers might be a crucial pathological basis for cognitive dysfunction.

Key words: type 1 diabetes, cognitive dysfunction, cerebral cortex, stereology, neurons, synapses

CLC Number:

R587.1

Yuanyu ZHAO,Min TAN,Hui ZHAO,Jing YANG,Feng ZHAO,Jiang DU. Effects of cortical neuronal and synaptic number changes on cognitive function in rats with type 1 diabetes mellitus⁃unbiased stereoscopic study[J]. The Journal of Practical Medicine, 2025, 41(13): 1997-2003.

Figures/Tables 6

Tab.1

Tab.2

Fig.1

Fig.2

Fig.3

Fig.4

References 33

[1]	BUZZETTI R， ZAMPETTI S， POZZILLI P. Impact of obesity on the increasing incidence of type 1 diabetes ［J］. Diabetes Obes Metab， 2020， 22（7）： 1009-1013. doi:10.1111/dom.14022 doi: 10.1111/dom.14022
[2]	李赞，刘喜洋，贺卓佳，等. 1999-2019年中国糖尿病疾病负担的调查研究［J］. 解放军医学杂志， 2024， 49（7）： 776-782.
[3]	PAUL S， ALI A， KATARE R. Molecular complexities underlying the vascular complications of diabetes mellitus - A comprehensive review ［J］. J Diabetes Complications， 2020， 34（8）： 107613. doi:10.1016/j.jdiacomp.2020.107613 doi: 10.1016/j.jdiacomp.2020.107613
[4]	SRIKANTH V， SINCLAIR A J， HILL-BRIGGS F， et al. Type 2 diabetes and cognitive dysfunction-towards effective management of both comorbidities ［J］. Lancet Diabetes Endocrinol， 2020， 8（6）： 535-545. doi:10.1016/s2213-8587(20)30118-2 doi: 10.1016/s2213-8587(20)30118-2
[5]	HOU Y， CHEN Z， CHENG J， et al. The Mechanism and Treatment of Cognitive Dysfunction in Diabetes： A Review ［J］. Exp Clin Endocrinol Diabetes， 2025， 133（2）： 64-72. doi:10.1055/a-2480-7826 doi: 10.1055/a-2480-7826
[6]	TEMPLER S， ABDO S， WONG T. Preventing diabetes complications ［J］. Intern Med J， 2024， 54（8）： 1264-1274. doi:10.1111/imj.16455 doi: 10.1111/imj.16455
[7]	杨欢，程笑，王月华，等. 糖尿病并发症中血脑屏障功能损伤机制研究进展［J］. 中国药学杂志， 2016（2）： 86-90.
[8]	YU K K K， CHEING G L Y， CHEUNG C， et al. Gray Matter Abnormalities in Type 1 and Type 2 Diabetes： A Dual Disorder ALE Quantification ［J］. Front Neurosci， 2021， 15： 638861. doi:10.3389/fnins.2021.638861 doi: 10.3389/fnins.2021.638861
[9]	VESTERGAARD M B， LAURSEN J C， HEINRICH N S， et al. Patients with type 1 diabetes and albuminuria have a reduced brain glycolytic capability that is correlated with brain atrophy ［J］. Front Neurosci， 2023， 17： 1229509. doi:10.3389/fnins.2023.1229509 doi: 10.3389/fnins.2023.1229509
[10]	XU Y， LIU S， ZHU L， et al. Green tea protects against hippocampal neuronal apoptosis in diabetic encephalopathy by inhibiting JNK/MLCK signaling ［J］. Mol Med Rep， 2021， 24（2）：575. doi:10.3892/mmr.2021.12214 doi: 10.3892/mmr.2021.12214
[11]	GARCíA-MAGRO N， MESA-LOMBARDO A， BARROS-ZULAICA N， et al. Impairment of synaptic plasticity in the primary somatosensory cortex in a model of diabetic mice ［J］. Front Cell Neurosci， 2024， 18： 1444395. doi:10.3389/fncel.2024.1444395 doi: 10.3389/fncel.2024.1444395
[12]	付勤，袁爱红，杨骏，等. 电针通过影响海马突触可塑性改善糖尿病认知减退大鼠的学习和记忆［J］. 中国病理生理杂志， 2024， 40（4）： 619-626.
[13]	HRISTOV M， NANKOVA A， ANDREEVA-GATEVA P. Alterations of the glutamatergic system in diabetes mellitus ［J］. Metab Brain Dis， 2024， 39（2）： 321-333. doi:10.1007/s11011-023-01299-z doi: 10.1007/s11011-023-01299-z
[14]	GONZALEZ-RODRIGUEZ M， VILLAR-CONDE S， ASTILLERO-LOPEZ V， et al. Human amygdala involvement in Alzheimer's disease revealed by stereological and dia-PASEF analysis ［J］.Brain Pathol， 2023， 33（5）： e13180. doi:10.1111/bpa.13180 doi: 10.1111/bpa.13180
[15]	SANCHEZ-PUELLES C， FRAJ A， CANO-DAGANZO V， et al. The Alzheimer multifactorial therapeutic agent E2F4DN prevents long-term potentiation and cognitive loss and improves neuronal survival in homozygous 5xFAD mice ［J］. Alzheimer's & Dementia， 2023， 19（S13）： e076606. doi:10.1002/alz.076606 doi: 10.1002/alz.076606
[16]	BAHADER G A， NASH K M， ALMARGHALANI D A， et al. Type-I diabetes aggravates post-hemorrhagic stroke cognitive impairment by augmenting oxidative stress and neuroinflammation in mice ［J］. Neurochemistry International， 2021， 149： 105151. doi:10.1016/j.neuint.2021.105151 doi: 10.1016/j.neuint.2021.105151
[17]	OZKAN A， ASLAN M A， SINEN O， et al. Effects of adropin on learning and memory in rats tested in the Morris water maze ［J］. Hippocampus， 2022， 32（4）： 253-263. doi:10.1002/hipo.23403 doi: 10.1002/hipo.23403
[18]	SADEGHINEZHAD J， NYENGAARD J R. Morphometry of cervical spinal cord in cat using design-based stereology ［J］. Anat Histol Embryol， 2021， 50（4）： 746-755. doi:10.1111/ahe.12719 doi: 10.1111/ahe.12719
[19]	范金花，周春妮，蒋林，等. 跑步锻炼延缓APP/PS1双转基因小鼠内侧前额叶皮质树突棘数量的丢失［J］. 第三军医大学学报， 2019， 41（14）： 8.
[20]	GUNDERSEN H J， JENSEN E B， KIêU K， et al. The efficiency of systematic sampling in stereology--reconsidered ［J］. J Microsc， 1999， 193（Pt 3）： 199-211. doi:10.1046/j.1365-2818.1999.00457.x doi: 10.1046/j.1365-2818.1999.00457.x
[21]	LLORIáN-SALVADOR M， CABEZA-FERNáNDEZ S， GOMEZ-SANCHEZ J A， et al. Glial cell alterations in diabetes-induced neurodegeneration ［J］. Cell Mol Life Sci， 2024， 81（1）： 47. doi:10.1007/s00018-023-05024-y doi: 10.1007/s00018-023-05024-y
[22]	曹晴祎，田毅，王金浓. 神经丝轻链蛋白与2型糖尿病认知功能障碍关系的研究进展［J］. 中国医学科学院学报， 2024， 46（1）： 98-103.
[23]	WĄTROBA M， GRABOWSKA A D， SZUKIEWICZ D. Effects of Diabetes Mellitus-Related Dysglycemia on the Functions of Blood-Brain Barrier and the Risk of Dementia ［J］. Int J Mol Sci， 2023， 24（12）：10069. doi:10.3390/ijms241210069 doi: 10.3390/ijms241210069
[24]	SASAKI-HAMADA S， FUJIWARA A， SATOH S， et al. GLP-2 restores impairments in spatial working memory and hippocampal LTD via the MEK/ERK pathway in juvenile-onset diabetes rats ［J］. Behav Brain Res， 2021， 406： 113235. doi:10.1016/j.bbr.2021.113235 doi: 10.1016/j.bbr.2021.113235
[25]	REYES-PARDO H， SÁNCHEZ-HERRERA D P， SANTILLáN M. On the effects of diabetes mellitus on the mechanical properties of DRG sensory neurons and their possible relation with diabetic neuropathy ［J］. Phys Biol， 2022， 19（4）： 046002. doi:10.1088/1478-3975/ac6722 doi: 10.1088/1478-3975/ac6722
[26]	陈秋旋，贺娅旎，刘玉香，等. Aβ42寡聚体对突触内外谷氨酸受体表达的影响［J］. 中国病理生理杂志， 2024， 40（6）： 1025-1032.
[27]	MATSUURA K， KOBAYASHI S， KONNO K， et al. SIPA1L1/SPAR1 Interacts with the Neurabin Family of Proteins and is Involved in GPCR Signaling ［J］.J Neurosci， 2022， 42（12）： 2448-2473. doi:10.1523/jneurosci.0569-21.2022 doi: 10.1523/jneurosci.0569-21.2022
[28]	SYAGE A R， PACHOW C， MURRAY K M， et al. Cystatin F attenuates neuroinflammation and demyelination following murine coronavirus infection of the central nervous system ［J］. J Neuroinflammation， 2024， 21（1）： 157. doi:10.1186/s12974-024-03153-0 doi: 10.1186/s12974-024-03153-0
[29]	SAFWAT S M， TOHAMY M EL， ABOONQ M S， et al. Vanillic Acid Ameliorates Demyelination in a Cuprizone-Induced Multiple Sclerosis Rat Model： Possible Underlying Mechanisms ［J］. Brain Sci， 2023， 14（1）：12. doi:10.3390/brainsci14010012 doi: 10.3390/brainsci14010012
[30]	CHEN W， WANG R， CHEN C. Cerebral Myelination in a Bronchopulmonary Dysplasia Murine Model ［J］. Children （Basel）， 2023， 10（8）：1321. doi:10.3390/children10081321 doi: 10.3390/children10081321
[31]	BOTELLA J， SCHYTZ C T， PEHRSON T F， et al. Increased mitochondrial surface area and cristae density in the skeletal muscle of strength athletes ［J］. J Physiol， 2023， 601（14）： 2899-2915. doi:10.1113/jp284394 doi: 10.1113/jp284394
[32]	LI Z G， ZHANG W， GRUNBERGER G， et al. Hippocampal neuronal apoptosis in type 1 diabetes ［J］. Brain Res， 2002， 946（2）： 221-231. doi:10.1016/s0006-8993(02)02887-1 doi: 10.1016/s0006-8993(02)02887-1
[33]	GISPEN W H， BIESSELS G J. Cognition and synaptic plasticity in diabetes mellitus ［J］. Trends Neurosci， 2000， 23（11）： 542-549. doi:10.1016/s0166-2236(00)01656-8 doi: 10.1016/s0166-2236(00)01656-8

组别	例数	体质量/g	血糖/（mmol/L）
组别	例数	体质量/g	实验前	第1周	实验后
对照组	5	391.60 ± 101.07	6.02 ± 0.72	4.98 ± 1.92	6.02 ± 1.09
糖尿病组	5	238.00 ± 41.43	6.28 ± 0.93	23.44 ± 2.94	27.10 ± 5.64
t值		3.144	0.494	11.756	8.206
P值		0.137	0.634	< 0.001	< 0.001

组别	例数	第1天	第2天	第3天	第4天	第5天
对照组	5	48.11 ± 10.35	25.63 ± 25.11	10.39 ± 5.67	5.21 ± 5.06	36.24 ± 5.12
糖尿病组	5	75.14 ± 20.59	49.75 ± 49.01	47.43 ± 39.08	40.25 ± 35.24	36.37 ± 5.44
t值		2.623	0.979	2.097	2.201	0.039
P值		0.031	0.356	0.069	0.059	0.970

Effects of cortical neuronal and synaptic number changes on cognitive function in rats with type 1 diabetes mellitus⁃unbiased stereoscopic study

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 6

References 33

Related Articles 8

Recommended Articles

Metrics

Comments

[1]	Jiadong WANG,Fangzhou HUANG,Yan HUANG,Guanxiong CHEN,Jun LIU,Peiqi. HUANG. Role of eupatilin in protection of mitochondrial function through Sesn2⁃Nrf2 in septic brain injury [J]. The Journal of Practical Medicine, 2024, 40(5): 601-607.
[2]	Ruyue XUE,Yuexian LI,Defeng. SUN. Research progress on stellate ganglion block improving postoperative cognitive dysfunction [J]. The Journal of Practical Medicine, 2024, 40(11): 1500-1504.
[3]	Yingxiu CHEN,Yingqi GUO,Huimei ZHANG,Qi ZHANG,Jinkun WEN,Li LUO,Lixia. LI. Proanthocyanidins promotes neurite outgrowth of dorsal root ganglion neurons in rat [J]. The Journal of Practical Medicine, 2024, 40(10): 1357-1363.
[4]	XU Qingbo, YANG Yu, YANG Li, XIE Liling, ZHANG Dongguang, HUANG Hui.. Research progress of gut microbiota and type 1 diabetes mellitus [J]. The Journal of Practical Medicine, 2023, 39(2): 142-147.
[5]	PENG Guanfa, WANG Lifeng, ZHONG Maolin, LIANG Weidong, YE Junming.. RNARole of noncoding RNA in the pathogenesis of postoperative cognitivedysfunction [J]. The Journal of Practical Medicine, 2022, 38(17): 2128-2132.
[6]	YE Kaiyun, JIANG Guanyiqing, LIANG Ganxiong, SHANG Zhixin, WU Weiying.. Effect of integrated medical management in patients with type 1 diabetes mellitus [J]. The Journal of Practical Medicine, 2022, 38(12): 1563-1568.
[7]	CHEN Yu, LIN Yan, YOU Tianhui. Influence factors of hypoglycemia in children with type 1 diabetes [J]. The Journal of Practical Medicine, 2021, 37(2): 264-267.
[8]	LI Xinlu, XU Hong, LIANG Xi. Efficacy of levetiracetam combined with oxcarbazepine in treatment of cognitive dysfunction of adult pa⁃tients with temporal lobe epilepsy [J]. The Journal of Practical Medicine, 2021, 37(1): 87-90.