Quantitative profiling of neurotransmitter abnormalities in brain, cerebrospinal fluid, and serum of experimental diabetic encephalopathy male rat

Han, Xiaowen; Min, Mengjun; Wang, Juan; Bao, Zejun; Fan, Huiying; Li, Xinyu; Adelusi, Temitope Isaac; Zhou, Xueyan; Yin, Xiaoxing

doi:10.1002/jnr.24098

Cited by 22 publications

(14 citation statements)

References 62 publications

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“…It may be due to different experimental designs, such as T1DM or T2DM, and different study specimens, such as cerebrospinal fluid, hippocampus, and urine (15)(16)(17)(18)(19). This animal model has also been established to explore its potential metabolic mechanisms based on the metabonomic approach between STZ-induced diabetic rats with cognitive impairment (DMMCI) and agematched groups (NC) when they focused on changes in cerebrospinal fluid, brain tissue, or urine metabolites (19)(20)(21), but to our knowledge serum metabolomics has been rarely reported.…”

Section: Discussionmentioning

confidence: 99%

LC-MS-Based Untargeted Metabolomics Reveals Early Biomarkers in STZ-Induced Diabetic Rats With Cognitive Impairment

et al. 2021

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Diabetes in the elderly increases cognitive impairment, but the underlying mechanisms are still far from fully understood. A non-targeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) was performed to screen out the serum biomarkers of diabetic mild cognitive impairment (DMMCI) in rats. Total 48 SD rats were divided into three groups, Normal control (NC) group, high-fat diet (HFD) fed group and type 2 diabetes mellitus (T2DM) group. The T2DM rat model was induced by intraperitoneal administration of streptozotocin (STZ, 35 mg/kg) after 6 weeks of high-fat diet (HFD) feeding. Then each group was further divided into 4-week and 8-week subgroups, which were calculated from the time point of T2DM rat model establishment. The novel object recognition test (NORT) and the Morris water maze (MWM) method were used to evaluate the cognitive deficits in all groups. Compared to the NC-8w and HFD-8w groups, both NOR and MWM tests indicated significant cognitive dysfunction in the T2DM-8w group, which could be used as an animal model of DMMCI. Serum was ultimately collected from the inferior vena cava after laparotomy. Metabolic profiling analysis was conducted using ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to verify the stability of the model. According to variable importance in the project (VIP > 1) and the p-value of t-test (P < 0.05) obtained by the OPLS-DA model, the metabolites with significant differences were screened out as potential biomarkers. In total, we identified 94 differentially expressed (44 up-regulated and 50 down-regulated) endogenous metabolites. The 10 top up-regulated and 10 top down-regulated potential biomarkers were screened according to the FDR significance. These biomarkers by pathway topology analysis were primarily involved in the metabolism of sphingolipid (SP) metabolism, tryptophan (Trp) metabolism, Glycerophospholipid (GP) metabolism, etc. Besides, SP metabolism, Trp metabolism and GP metabolism mainly belonging to the lipid metabolism showed marked perturbations over DMMCI and may contribute to the development of disease. Taken collectively, our results revealed that T2DM could cause cognitive impairment by affecting a variety of metabolic pathways especially lipid metabolism. Besides, serum PE, PC, L-Trp, and S1P may be used as the most critical biomarkers for the early diagnosis of DMMCI.

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Section: Discussionmentioning

confidence: 99%

LC-MS-Based Untargeted Metabolomics Reveals Early Biomarkers in STZ-Induced Diabetic Rats With Cognitive Impairment

et al. 2021

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“…Diabetes mellitus (DM) is a chronic and common metabolic disease with a worldwide prevalence and is associated with high glucose and a deficit in insulin production or sensitivity [1]. Diabetic encephalopathy is one of the main complications of DM [2], it is characterized by atrophy of the brain (gray matter and hippocampus), changes in cerebrovascular morphology and function, impairment of synaptic plasticity, and dysfunction of neuroglia [3]. Patients with DM show neuropsychiatric disorders, and emerging epidemical studies indicate that DM has a close relationship with depression.…”

Section: Introductionmentioning

confidence: 99%

Gastrodin Alleviates Cognitive Dysfunction and Depressive-Like Behaviors by Inhibiting ER Stress and NLRP3 Inflammasome Activation in db/db Mice

Ye¹,

Meng

Wang

et al. 2018

IJMS

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Patients with diabetes mellitus (DM) suffer more risks from diabetic encephalopathy such as cognitive dysfunction and depressive-like behaviors. Numerous studies show that ER (endoplasmic reticulum) stress and inflammation play important roles in the development of diabetic encephalopathy. Gastrodin (Gas), one major component of Gastrodia elata, is traditionally used in central nervous system disorders and is believed to possess anti-inflammatory, anti-apoptotic, and other neuroprotective effects. This present study aims to explore the protective effects of Gas on diabetic encephalopathy. Gas was administrated daily (70 and 140 mg/Kg) for 12 weeks. Meanwhile, the fasting blood glucose and body weight of db/db mice were measured every two weeks. After Gas treatment, the Morris water maze (MWM) test and novel object recognition (NOR) test were performed to assess the learning and memory functions of db/db mice, and the forced swim test was performed to evaluate depressive-like behaviors of db/db mice. Additionally, the expression of ER stress and Nucleotide binding and oligomerization domain-like (Nod) receptor family pyrin domain-containing 3 (NLRP3) inflammasome related proteins were evaluated by using Western blot. Our study suggested that Gas attenuated blood glucose levels and dyslipidemia of db/db mice. It has been shown that Gas could improve learning and memory function and depressive-like behaviors of db/db mice. Moreover, Gas inhibited ER stress and NLRP3 inflammasome activation in the hippocampus. Taken together, this study demonstrates that Gas attenuates the diabetic encephalopathy by inhibiting ER stress and NLRP3 inflammasome activation.

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“…The decrease of 5-HT level in the pineal gland as a result of streptozotocin-induced diabetes is of special interest in terms of more general aspects concerning the effect of diabetes on the prevalence of depressive disorders in humans [ 51 ], which could be related to changes in serotoninergic brain systems. The decreased content of 5-HT was demonstrated in the brain cortex, hippocampus, striatum, and cerebrospinal fluid of rats with streptozotocin-induced diabetic encephalopathy, compared to control animals [ 52 ]. Changes in serotonin metabolism were also reported in streptozotocin-induced diabetic mice [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Streptozotocin-Induced Diabetes on the Pineal Gland in the Domestic Pig

Lewczuk

Prusik

Ziółkowska

et al. 2018

IJMS

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Several observations from experiments in rodents and human patients suggest that diabetes affects pineal gland function, including melatonin secretion; however, the accumulated data are not consistent. The aim of the present study was to determine the effects of streptozotocin-induced diabetes on the pineal gland in the domestic pig, a species widely used as a model in various biomedical studies. The study was performed on 10 juvenile pigs, which were divided into two groups: control and diabetic. Diabetes was evoked by administration of streptozotocin (150 mg/kg of body weight). After six weeks, the animals were euthanized between 12.00 and 14.00, and the pineal glands were removed and divided into two equal parts, which were used for biochemical analyses and for preparation of explants for the superfusion culture. The pineal contents (per 100 μg protein) of serotonin, 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid, 5-methoxytryptophol, and 5-methoxytryptamine were significantly lower in diabetic pigs than in control pigs. In contrast, the level of N-acetylserotonin was significantly higher in diabetic animals. No significant differences were found in the level of melatonin between control and experimental pigs. The amounts of 3,4-dihydroxyphenylalanine, dopamine, norepinephrine, and 3,4-dihydroxyphenylacetic acid were significantly lower in the pineal glands of diabetic animals. The level of vanillylmandelic acid was higher in diabetic pigs. No differences were observed in the level of basal and NE-stimulated release of N-acetylserotonin or melatonin between the pineal explants prepared from control and experimental animals. In vitro treatment with insulin was ineffective. In conclusion, streptozotocin-induced diabetes affects both indole metabolism and adrenergic neurotransmission in the pig pineal gland.

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Quantitative profiling of neurotransmitter abnormalities in brain, cerebrospinal fluid, and serum of experimental diabetic encephalopathy male rat

Cited by 22 publications

References 62 publications

LC-MS-Based Untargeted Metabolomics Reveals Early Biomarkers in STZ-Induced Diabetic Rats With Cognitive Impairment

LC-MS-Based Untargeted Metabolomics Reveals Early Biomarkers in STZ-Induced Diabetic Rats With Cognitive Impairment

Gastrodin Alleviates Cognitive Dysfunction and Depressive-Like Behaviors by Inhibiting ER Stress and NLRP3 Inflammasome Activation in db/db Mice

Effects of Streptozotocin-Induced Diabetes on the Pineal Gland in the Domestic Pig

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