Cognitive impairments in type 1 diabetes mellitus model mice are associated with synaptic protein disorders

Wang, Yiming; Yang, Yueqi; Liu, Y.; Guo, Angyang; Zhang, Yan

doi:10.1016/j.neulet.2022.136587

Cited by 13 publications

(7 citation statements)

References 39 publications

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“…1A), unlike what was observed by Raymundi et al (2020) in non-diabetic animals. This difference between nondiabetic and STZ animals after acute treatment with CBD is not surprising as several studies demonstrate that experimental T1DM induces encephalopathy in these animals characterised by increased oxidative stress and neuroinflammation, dysregulation of the neurotransmitter systems, impaired synaptic plasticity, and neurogenesis (Waltrick et al, 2022: Wang et al, 2022Redivo et al, 2016;da Silva Dias et al, 2016;Zhao et al, 2016;de Morais et al, 2014de Morais et al, , 2016. In addition, studies have already reported that the endogenous cannabinoid system of STZ animals seems to be dysregulated (Duarte et al, 2007;de Morais et al, 2016).…”

Section: Discussionmentioning

confidence: 97%

“…At this point, it is important to reinforce that changes in several brain areas have been implicated in this impaired regulation of emotions and fear-related memory, including the hippocampus. For example, preclinical findings have demonstrated in the hippocampus from experimental T1DM animals increased neuroinflammation and oxidative stress-related parameters along with dysregulation of the neurotransmitter systems, impaired synaptic plasticity, and neurogenesis (Wang et al, 2022;Waltrick et al, 2022;Redivo et al, 2016;da Silva Dias et al, 2016;Zhao et al, 2016;de Morais et al, 2014de Morais et al, , 2016. In the same direction, clinical studies showed significant changes in this same brain area of diabetic individuals associated with cognitive decline (Hamed, 2017;Moheet et al, 2015), being these changes also linked to an increased predisposition to anxiety and stress-related disorders, such as PTSD (Renna et al, 2016;Bystritsky et al, 2014).…”

Section: Introductionmentioning

confidence: 96%

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Cannabidiol modulates contextual fear memory consolidation in animals with experimentally induced type-1 diabetes mellitus

Chaves

Raymundi

Waltrick

et al. 2023

Acta Neuropsychiatr.

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Objectives: In view of the neuroprotective characteristic of cannabidiol (CBD) and its beneficial action on aversive memory in non-diabetic animals, we aimed to investigate in animals with experimentally induced type-1 diabetes mellitus (T1DM) whether CBD treatment would be able to impair the contextual fear memory consolidation, its generalization and whether the effect would be lasting. We also investigated the CBD effect on anxiety-like responses. Methods: After T1DM induction, animals received single or more prolonged treatment with CBD and were submitted to the contextual fear conditioning (CFC) test. As expression of activity-regulated cytoskeletal-associated (Arc) protein is necessary for memory consolidation, we evaluated its expression in the dorsal hippocampus (DH). For evaluating anxiety-related responses, animals were submitted to the elevated plus maze test (EPMT), in which the time and number of entries in the open arms were used as anxiety index. Results: A single injection of CBD impaired the contextual fear memory consolidation and its generalization, which was evaluated by exposing the animal in a neutral context. This single injection was able to reduce the elevated expression of Arc in the DH from these animals. Interestingly, more prolonged treatment with CBD also impaired the persistence of context-conditioned fear memory and induced an anxiolytic-like effect, as the treated group spent more time in the open arms of the EPMT. Conclusion: CBD interferes with contextual fear memory and the dosage regimen of treatment seems to be important. Moreover, we cannot rule out the involvement of emotional aspects in these processes related to fear memory.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 96%

Cannabidiol modulates contextual fear memory consolidation in animals with experimentally induced type-1 diabetes mellitus

Chaves

Raymundi

Waltrick

et al. 2023

Acta Neuropsychiatr.

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“…High glucose treatment triggers AIS elongation accompanied by increased neuronal excitability. Neurons from 270 kDa AnkG-expressing mice display reduced AIS plasticity, while neurons from 480 kDa AnkG-expressing mice exhibit restoration of AIS plasticity and dual spacing of the AIS lattice structure after glucose treatment ( Wang et al, 2022a ).…”

Section: Potential Late-onset Sad Models and MCI Modelsmentioning

confidence: 99%

Animal models of Alzheimer’s disease: Applications, evaluation, and perspectives

Chen

Zhang

2022

Zoological Research

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Although great advances in elucidating the molecular basis and pathogenesis of Alzheimer’s disease (AD) have been made and multifarious novel therapeutic approaches have been developed, AD remains an incurable disease. Evidence shows that AD neuropathology occurs decades before clinical presentation. AD is divided into three stages: preclinical stage, mild cognitive impairment (MCI), and AD dementia. In the natural world, some animals, such as non-human primates (NHPs) and canines, can develop spontaneous AD-like dementia. However, most animals do not develop AD. With the development of transgenic techniques, both invertebrate and vertebrate animals have been employed to uncover the mechanisms of AD and study treatment methods. Most AD research focuses on early-onset familial AD (FAD) because FAD is associated with specific genetic mutations. However, there are no well-established late-onset sporadic AD (SAD) animal models because SAD is not directly linked to any genetic mutation, and multiple environmental factors are involved. Moreover, the widely used animal models are not able to sufficiently recapitulate the pathological events that occur in the MCI or preclinical stages. This review summarizes the common models used to study AD, from yeast to NHP models, and discusses the different applications, evaluation methods, and challenges related to AD animal models, as well as prospects for the evolution of future studies.

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“…Bununla birlikte reboksetin'in SSS'de diyabet ile indüklenen moleküler düzeydeki bozuklukları restore etmiş olması da mümkün olabilir. Nitekim reboksetin'in de üyesi olduğu antidepresan ilaçların diyabetik deneklerin beyinlerindeki yetersiz LTP indüksiyonunu, azalan sinaptik protein seviyelerini (sinaptofizin, postsinaptik yoğunluk 95 gibi) ve zayıflayan sinaptik gücü [75,76] iyileştirme potansiyeline sahip oldukları bilinmektedir [73,[77][78][79]. Bu düşünceyi destekler nitlikte olmak üzere; araştırma grubumuz tarafından daha önce yapılan bir çalışmada antidepresan bir ilaç olan agomelatin'in (40 ve 80 mg/kg, 2 hafta) STZ-diyabetik sıçanların öğrenme ve bellek performanslarında kayda değer bir iyileşme sağladığı ve bu hayvanların beyinlerinde hipokampal alt alanlardaki nöron kayıplarını önlediği gösterilmiştir [80].…”

Section: Morris Su Tankı Testine İlişkin Bulgularunclassified

Rebokseti̇n’i̇n Di̇yabeti̇k Siçanlarda Bozulmuş Davraniş Parametreleri̇ Üzeri̇ndeki̇ Yararli Etki̇leri̇

Yücel

Kandemir

Üçel

et al. 2022

Ankara Ecz. Fak. Derg.

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Amaç: Diyabetik hastalarda duygu-durum hastalıklarının ve kognitif bozukluk insidansının genel popülasyona oranla daha yüksek olduğu bilinmektedir. Bu çalışmada, klinikte antidepresan etkinliği için reçete edilen reboksetin’in sıçanlarda diyabet ile indüklenen davranışsal ve bilişsel değişiklikler üzerine etkinliğinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Sıçanlarda deneysel diyabet modeli 50 mg/kg tek doz streptozotosin enjeksiyonu (i.v.) ile oluşturulnuştur. Reboksetin tedavisine diyabetik komplikasyonların oluşması için 4 hafta beklendikten sonra başlanmıştır. Deney hayvanlarının depresyon ve anksiyete düzeyleri sırasıyla modifiye zorlu yüzme ve yükseltilmiş artı şekilli labirent testleri ile araştırılmış; kognitif performansları ise Morris su tankı ve pasif sakınma testleri ie değerlendirilmiştir. Hayvanlarının motor aktiviteleri de aktivite kafesi ve Rota-rod testleri ile incelenmiştir. Sonuç ve Tartışma: Deneyler sonucunda, diyabetik sıçanların depresyon ve anksiyete düzeylerinin yükseldiği ve bilişsel performanslarının zayıfladığı belirlenmiştir. İki hafta süre ile uygulanan reboksetin tedavisi (8 ve 16 mg/kg) diyabetik sıçanların yüksek depresyon ve anksiyete düzeylerini azaltırken, zayıflamış olan bilişsel performanslarını kayda değer ölçüde güçlendirmiştir. Elde edilen bulgular reboksetin’in diyabete bağlı olarak ortaya çıkan davranışsal ve bilişsel bozuklukların tedavisinde terapötik bir potansiyele sahip olabileceğine işaret etmiştir.

show abstract

Cognitive impairments in type 1 diabetes mellitus model mice are associated with synaptic protein disorders

Cited by 13 publications

References 39 publications

Cannabidiol modulates contextual fear memory consolidation in animals with experimentally induced type-1 diabetes mellitus

Cannabidiol modulates contextual fear memory consolidation in animals with experimentally induced type-1 diabetes mellitus

Animal models of Alzheimer’s disease: Applications, evaluation, and perspectives

Rebokseti̇n’i̇n Di̇yabeti̇k Siçanlarda Bozulmuş Davraniş Parametreleri̇ Üzeri̇ndeki̇ Yararli Etki̇leri̇

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