Effects of 20-hydroxyecdysone on improving memory deficits in streptozotocin-induced type 1 diabetes mellitus in rat

Xia, Xuan; Zhang, Qingyuan; Liu, Rongzhi; Wang, Zhongxiao; Tang, Nianya; Liu, Fei; Huang, Guosheng; Jiang, Xiao Ling; Gui, Gaixia; Wang, Lijuan; Sun, Xiuli

doi:10.1016/j.ejphar.2014.06.026

Cited by 33 publications

(25 citation statements)

References 22 publications

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“…It is well known that BDNF binds to tropomyosin-related kinase receptor B (TrkB), induces autophosphorylation of TrkB, and then triggers several signaling cascades that affect multiple cellular processes [21]. The expression level of BDNF is significantly decreased in the hippocampus of both type 1 and type 2 diabetes rats [11, 12]. Therefore, we examined the level of phosphorylated TrkB after BDNF overexpression in the hippocampus.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, it was reported that low expression levels of BDNF are associated with cognitive deficits in patients with diabetes [10]. The expression level of BDNF is significantly decreased in the hippocampus of both type 1 and type 2 diabetes rats [11, 12]. To date, however, whether BDNF is sufficient to mitigate synaptic impairments and reduce neuroinflammation in the diabetic brain has not been investigated.…”

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confidence: 99%

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BDNF Alleviates Neuroinflammation in the Hippocampus of Type 1 Diabetic Mice via Blocking the Aberrant HMGB1/RAGE/NF-κB Pathway

Han¹,

Liu²,

Sun³

et al. 2019

Aging and disease

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Diabetes is a systemic disease that can cause brain damage such as synaptic impairments in the hippocampus, which is partly because of neuroinflammation induced by hyperglycemia. Brain-derived neurotrophic factor (BDNF) is essential in modulating neuroplasticity. Its role in anti-inflammation in diabetes is largely unknown. In the present study, we investigated the effects of BDNF overexpression on reducing neuroinflammation and the underlying mechanism in mice with type 1 diabetes induced by streptozotocin (STZ). Animals were stereotactically microinjected in the hippocampus with recombinant adeno-associated virus (AAV) expressing BDNF or EGFP. After virus infection, four groups of mice, the EGFP+STZ, BDNF+STZ, EGFP Control and BDNF Control groups, received STZ or vehicle treatment as indicated. Three weeks later brain tissues were collected. We found that BDNF overexpression in the hippocampus significantly rescued STZ-induced decreases in mRNA and protein expression of two synaptic plasticity markers, spinophilin and synaptophysin. More interestingly, BDNF inhibited hyperglycemia-induced microglial activation and reduced elevated levels of inflammatory factors (TNF-α, IL-6). BDNF blocked the increase in HMGB1 levels and specifically, in levels of one of the HMGB1 receptors, RAGE. Downstream of HMGB1/RAGE, the increase in the protein level of phosphorylated NF-κB was also reversed by BDNF in STZ-treated mice. These results show that BDNF overexpression reduces neuroinflammation in the hippocampus of type 1 diabetic mice and suggest that the HMGB1/RAGE/NF-κB signaling pathway may contribute to alleviation of neuroinflammation by BDNF in diabetic mice.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

BDNF Alleviates Neuroinflammation in the Hippocampus of Type 1 Diabetic Mice via Blocking the Aberrant HMGB1/RAGE/NF-κB Pathway

Han¹,

Liu²,

Sun³

et al. 2019

Aging and disease

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“…Their function in plants is unclear; however, they may be involved in the deterrence of invertebrate predators by acting as antifeed-systems, or yet by interfering in the ingestion of phytophagous insects ( 16 ). In mammals, 20E has demonstrated therapeutic properties including memory improvement, reduction of lipid storage and anabolic effects ( 28 – 30 ).…”

Section: Discussionmentioning

confidence: 99%

Sida tuberculata (Malvaceae): a study based on development of extractive system and in silico and in vitro properties

Rosa

Salgueiro

Colpo

et al. 2016

Braz J Med Biol Res

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Sida tuberculata (Malvaceae) is a medicinal plant traditionally used in Brazil as an antimicrobial and anti-inflammatory agent. Here, we aimed to investigate the different extractive techniques on phytochemical parameters, as well as to evaluate the toxicity and antioxidant capacity of S. tuberculata extracts using in silico and in vitro models. Therefore, in order to determine the dry residue content and the main compound 20-hydroxyecdysone (20E) concentration, extracts from leaves and roots were prepared testing ethanol and water in different proportions. Extracts were then assessed by Artemia salina lethality test, and toxicity prediction of 20E was estimated. Antioxidant activity was performed by DPPH and ABTS radical scavenger assays, ferric reducing power assay, nitrogen derivative scavenger, deoxyribose degradation, and TBARS assays. HPLC evaluation detected 20E as main compound in leaves and roots. Percolation method showed the highest concentrations of 20E (0.134 and 0.096 mg/mL of extract for leaves and roots, respectively). All crude extracts presented low toxic potential on A. salina (LD50 >1000 µg/mL). The computational evaluation of 20E showed a low toxicity prediction. For in vitro antioxidant tests, hydroethanolic extracts of leaves were most effective compared to roots. In addition, hydroethanolic extracts presented a higher IC50 antioxidant than aqueous extracts. TBARS formation was prevented by leaves hydroethanolic extract from 0.015 and 0.03 mg/mL and for roots from 0.03 and 0.3 mg/mL on egg yolk and rat tissue, respectively (P<0.05). These findings suggest that S. tuberculata extracts are a considerable source of ecdysteroids and possesses a significant antioxidant property with low toxic potential.

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“…Other factors that regulate the dendritic arbor and number of dendritic spines include neurotrophins such as BDNF (for reviews see Bennett and Logopoulus, 2014; Leal et al, ). In STZ‐induced diabetes in rats, the BDNF content and expression has been reported reduced in the hippocampus (Agrawal et al, ; Chen et al, ; Liu et al, ; Mao et al, ; Xia et al, ). Another important factor involved in the regulation of the dendritic plasticity is oxidative stress (for the review see Muriach et al, ).…”

Section: Discussionmentioning

confidence: 99%

Cerebrolysin reverses hippocampal neural atrophy in a mice model of diabetes mellitus type 1

Sanchez-Vega

Juárez

Gómez-Villalobos

et al. 2015

Synapse

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The animal model of streptozotocin-induced diabetes mellitus type 1 (DM1) is used to study neuronal and behavioral changes produced by an increase in blood-glucose levels. Our previous report showed that chronic streptozotocin administration induced atrophy of dendritic morphology of pyramidal neurons of the CA1 dorsal hippocampus. In addition, we showed that Cerebrolysin (Cbl), a neurotrophic peptide mixture, reduces the dendritic atrophy in animal models of aging. This study aimed to determine whether Cbl was capable of reducing behavioral and neuronal alterations, after 6 weeks of hyperglycemia in mice (streptozotocin-induced DM1). The levels of glucose in the blood were evaluated before and after streptozotocin administration and only animals with more than 240 mg/dL of blood-levels of glucose were used. After streptozotocin treatment, the mice received 6 weeks of Cbl, locomotor activity was measured and dendritic morphological changes were evaluated using Golgi-Cox stain procedure, and analyzed by the Sholl method. In mice treated with streptozotocin there was a clear reduction in the dendritic length of pyramidal neurons of the CA1 and granular cells of the dental gyrus of the dorsal hippocampus. Interestingly, Cbl reversed the morphological changes induced by streptozotocin. Our results extend the list of abnormal morphological changes detected in this model of DM, and support the possibility that Cbl may have beneficial effects in the management of brain alterations induced by DM.

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Effects of 20-hydroxyecdysone on improving memory deficits in streptozotocin-induced type 1 diabetes mellitus in rat

Cited by 33 publications

References 22 publications

BDNF Alleviates Neuroinflammation in the Hippocampus of Type 1 Diabetic Mice via Blocking the Aberrant HMGB1/RAGE/NF-κB Pathway

BDNF Alleviates Neuroinflammation in the Hippocampus of Type 1 Diabetic Mice via Blocking the Aberrant HMGB1/RAGE/NF-κB Pathway

Sida tuberculata (Malvaceae): a study based on development of extractive system and in silico and in vitro properties

Cerebrolysin reverses hippocampal neural atrophy in a mice model of diabetes mellitus type 1

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