Neurodegenerative Changes in Rat Brain in Streptozotocin Model of Alzheimer’s Disease

Воронков, Д. Н.; Stavrovskaya, A. V.; Stelmashook, E. V.; Генрихс, Е. Е.; Isaev, N. K.

doi:10.1007/s10517-019-04442-y

Cited by 10 publications

(4 citation statements)

References 11 publications

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“…Follow-up period after the injection: the majority of the published studies applied a one month long post-injection period (Li et al, 2012;Correia et al, 2013;Zhou et al, 2013;Hashemi-Firouzi et al, 2018;Zappa Villar et al, 2018) or even shorter, 2-3 weeks intervals (Blokland and Jolles, 1993;Sonkusare et al, 2005;Jee et al, 2008;Deng et al, 2009;Yamini et al, 2018). There are some studies where longer, 3 months follow-up periods were used (Salkovic-Petrisic et al, 2006, Salkovic-Petrisic et al, 2011Knezovic et al, 2015;Samy et al, 2016; Knezovic et al, 2018;Ilieva et al, 2019;Voronkov et al, 2019) In two very much informative longitudinal studies (Knezovic et al, 2015;Osmanovic Barilar et al, 2015) changes/impairments were followed up to 9 months. In our study we chose a 3-3.5 months follow up period considering that the method is intended to be a model of Alzheimer's disease, which would imply slowly evolving long term pathological changes and that it allowed to conduct learning tasks requiring several weeks training, like 5-CSRTT.…”

Section: Discussionmentioning

confidence: 99%

Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats

et al. 2021

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Intracerebroventricularly injected streptozotocin (STZ)-induced learning impairment has been an increasingly used rat model of Alzheimer disease. The evoked pathological changes involve many symptoms of the human disease (cognitive decline, increase in β-amyloid and phospho-tau level, amyloid plaque-like deposits). However, the model has predominantly been used with Wistar rats in the literature. The objective of the current study was to transfer it to Long-Evans rats with the ulterior aim to integrate it in a complex cognitive test battery where we use this strain because of its superior cognitive capabilities. We performed two experiments (EXP1, EXP2) with three months old male animals. At EXP1, rats were treated with 2 × 1.5 mg/kg STZ (based on the literature) or citrate buffer vehicle injected bilaterally into the lateral ventricles on days 1 and 3. At EXP2 animals were treated with 3 × 1.5 mg/kg STZ or citrate buffer vehicle injected in the same way as in EXP1 at days 1, 3, and 5. Learning and memory capabilities of the rats were then tested in the following paradigms: five choice serial reaction time test (daily training, started from week 2 or 8 post surgery in Exp1 or Exp2, respectively, and lasting until the end of the experiment); novel object recognition (NOR) test (at week 8 or 14), passive avoidance (at week 11 or 6) and Morris water-maze (at week 14 or 6). 15 or 14 weeks after the STZ treatment animals were sacrificed and brain phospho-tau/tau protein ratio and β -amyloid level were determined by western blot technique. In EXP1 we could not find any significant difference between the treated and the control groups in any of the assays. In EXP2 we found significant impairment in the NOR test and elevated β-amyloid level in the STZ treated group in addition to slower learning of the five-choice paradigm and a trend for increased phospho-tau/tau ratio. Altogether our findings suggest that the Long-Evans strain may be less sensitive to the STZ treatment than the Wistar rats and higher doses may be needed to trigger pathological changes in these animals. The results also highlight the importance of strain diversity in modelling human diseases.

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Section: Discussionmentioning

confidence: 99%

Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats

et al. 2021

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“…Most studies using the ICV-STZ model are focused on the description of the behavioral [ 20 ] and morphological [ 21 ] aspects of the disease. The molecular factors of the ICV-STZ model are often assessed through techniques that target only a few genes, such as qRT-PCR [ 22 ] and Western blot [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of a Rat Streptozotocin Model Shows Dysregulated Biological Pathways Implicated in Alzheimer’s Disease

da Silva,

Fischer,

Souza

et al. 2024

IJMS

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Alzheimer’s Disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory loss and cognitive impairment, affecting 35 million individuals worldwide. Intracerebroventricular (ICV) injection of low to moderate doses of streptozotocin (STZ) in adult male Wistar rats can reproduce classical physiopathological hallmarks of AD. This biological model is known as ICV-STZ. Most studies are focused on the description of behavioral and morphological aspects of the ICV-STZ model. However, knowledge regarding the molecular aspects of the ICV-STZ model is still incipient. Therefore, this work is a first attempt to provide a wide proteome description of the ICV-STZ model based on mass spectrometry (MS). To achieve that, samples from the pre-frontal cortex (PFC) and hippocampus (HPC) of the ICV-STZ model and control (wild-type) were used. Differential protein abundance, pathway, and network analysis were performed based on the protein identification and quantification of the samples. Our analysis revealed dysregulated biological pathways implicated in the early stages of late-onset Alzheimer’s disease (LOAD), based on differentially abundant proteins (DAPs). Some of these DAPs had their mRNA expression further investigated through qRT-PCR. Our results shed light on the AD onset and demonstrate the ICV-STZ as a valid model for LOAD proteome description.

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“…An increasing number of studies have shown that intracerebroventricular (ICV) injection of streptozotocin, a glucosamine-nitrosourea compound with diabetogenic action, triggers a sporadic AD-like pathology. [14][15][16] In this study, we aimed to assess the effects of a posttraining MFB-ICSS treatment on spatial learning and memory, neurodegeneration, and serum expression of 14 neural plasticity-related miRNAs in a rat model of sporadic AD created by ICV injection of streptozotocin. The first experiment was designed to confirm whether rats that received streptozotocin exhibited the main hallmarks of AD according to the references mentioned above.…”

Section: Introductionmentioning

confidence: 99%

Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease

Riberas-Sánchez,

Puig-Parnau,

Vila-Solés

et al. 2024

jpn

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Background The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs. Methods We performed Morris water maze and light–dark transition tests. Levels of various proteins, specifically amyloid-β precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction. Results Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS. Limitations The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest. Conclusion Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.

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Neurodegenerative Changes in Rat Brain in Streptozotocin Model of Alzheimer’s Disease

Cited by 10 publications

References 11 publications

Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats

Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats

Proteomic Analysis of a Rat Streptozotocin Model Shows Dysregulated Biological Pathways Implicated in Alzheimer’s Disease

Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease

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