The GSK3β inhibitor, TDZD-8, rescues cognition in a zebrafish model of okadaic acid-induced Alzheimer's disease

Koehler, Daniel; Shah, Zahoor A.; Williams, Frederick

doi:10.1016/j.neuint.2018.10.022

Cited by 44 publications

(32 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quantification and analysis of the expression of GLT-1, NR2A, NR2B, HMGB1, RAGE, TNF-α, and β-tubulin blots were performed using ImageJ software (v1.53a). Water-control group data were represented as 100% (relative to water-control) to assess any changes in the expression of protein of interest in the AcbCo and AcbSh as described in our previous studies [62][63][64][65][66][67]. Therefore, in the same gel run, the expression of the protein in each group was normalized to the average values of the water-control group.…”

Section: Western Blot Analysesmentioning

confidence: 99%

Ampicillin/Sulbactam Treatment Modulates NMDA Receptor NR2B Subunit and Attenuates Neuroinflammation and Alcohol Intake in Male High Alcohol Drinking Rats

et al. 2020

View full text Add to dashboard Cite

Exposure to ethanol commonly manifests neuroinflammation. Beta (β)-lactam antibiotics attenuate ethanol drinking through upregulation of astroglial glutamate transporters, especially glutamate transporter-1 (GLT-1), in the mesocorticolimbic brain regions, including the nucleus accumbens (Acb). However, the effect of β-lactam antibiotics on neuroinflammation in animals chronically exposed to ethanol has not been fully investigated. In this study, we evaluated the effects of ampicillin/sulbactam (AMP/SUL, 100 and 200 mg/kg, i.p.) on ethanol consumption in high alcohol drinking (HAD1) rats. Additionally, we investigated the effects of AMP/SUL on GLT-1 and N-methyl-d-aspartate (NMDA) receptor subtypes (NR2A and NR2B) in the Acb core (AcbCo) and Acb shell (AcbSh). We found that AMP/SUL at both doses attenuated ethanol consumption and restored ethanol-decreased GLT-1 and NR2B expression in the AcbSh and AcbCo, respectively. Moreover, AMP/SUL (200 mg/kg, i.p.) reduced ethanol-increased high mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in the AcbSh. Moreover, both doses of AMP/SUL attenuated ethanol-elevated tumor necrosis factor-alpha (TNF-α) in the AcbSh. Our results suggest that AMP/SUL attenuates ethanol drinking and modulates NMDA receptor NR2B subunits and HMGB1-associated pathways.

show abstract

Section: Western Blot Analysesmentioning

confidence: 99%

Ampicillin/Sulbactam Treatment Modulates NMDA Receptor NR2B Subunit and Attenuates Neuroinflammation and Alcohol Intake in Male High Alcohol Drinking Rats

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In addition, PrP C inihibits GSK3β activity [36], and the kinase is proposed as playing a central role in AD under the GSK3 hypothesis [57] as it is involved in the mechanisms underlying learning and memory, the hyperphosphorylation of tau, the increased production of Aβ, local cerebral inflammatory responses, and finally in tau exon 10 splicing [19,21,43]. In fact, the neuroprotective role of GSK3 inhibitors in cellular and animal models of AD has been widely reported [58][59][60][61] and it continues to be a topic of study and clinical investigation [62]. To date, the consequences of the PrP C inhibitory effect on GSK3β have been associated…”

Section: Discussionmentioning

confidence: 99%

Tau Exon 10 Inclusion by PrPC through Downregulating GSK3β Activity

Lidón

Llaó-Hierro

Aguzzi

et al. 2021

IJMS

View full text Add to dashboard Cite

Tau protein is largely responsible for tauopathies, including Alzheimer’s disease (AD), where it accumulates in the brain as insoluble aggregates. Tau mRNA is regulated by alternative splicing, and inclusion or exclusion of exon 10 gives rise to the 3R and 4R isoforms respectively, whose balance is physiologically regulated. In this sense, one of the several factors that regulate alternative splicing of tau is GSK3β, whose activity is inhibited by the cellular prion protein (PrPC), which has different physiological functions in neuroprotection and neuronal differentiation. Moreover, a relationship between PrPC and tau expression levels has been reported during AD evolution. For this reason, in this study we aimed to analyze the role of PrPC and the implication of GSK3β in the regulation of tau exon 10 alternative splicing. We used AD human samples and mouse models of PrPC ablation and tau overexpression. In addition, we used primary neuronal cultures to develop functional studies. Our results revealed a paralleled association between PrPC expression and tau 4R isoforms in all models analyzed. In this sense, reduction or ablation of PrPC levels induces an increase in tau 3R/4R balance. More relevantly, our data points to GSK3β activity downstream from PrPC in this phenomenon. Our results indicate that PrPC plays a role in tau exon 10 inclusion through the inhibitory capacity of GSK3β.

show abstract

“…The behavior is recorded by camera and the time spent on finding the objective is quantified. A simple apparatus and procedure have been developed based on the T-maze (Williams et al, 2002;Koehler et al, 2018: Koehler et al, 2019. The tank is separated by a central white divider and adequate space at the bottom is reserved for zebrafish to swim freely between the two sections.…”

Section: T/y-maze Testmentioning

confidence: 99%

Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery

Wang

Zhang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Neurodegenerative disease (NDD), including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by the progressive loss of neurons which leads to the decline of motor and/or cognitive function. Currently, the prevalence of NDD is rapidly increasing in the aging population. However, valid drugs or treatment for NDD are still lacking. The clinical heterogeneity and complex pathogenesis of NDD pose a great challenge for the development of disease-modifying therapies. Numerous animal models have been generated to mimic the pathological conditions of these diseases for drug discovery. Among them, zebrafish (Danio rerio) models are progressively emerging and becoming a powerful tool for in vivo study of NDD. Extensive use of zebrafish in pharmacology research or drug screening is due to the high conserved evolution and 87% homology to humans. In this review, we summarize the zebrafish models used in NDD studies, and highlight the recent findings on pharmacological targets for NDD treatment. As high-throughput platforms in zebrafish research have rapidly developed in recent years, we also discuss the application prospects of these new technologies in future NDD research.

show abstract

The GSK3β inhibitor, TDZD-8, rescues cognition in a zebrafish model of okadaic acid-induced Alzheimer's disease

Cited by 44 publications

References 45 publications

Ampicillin/Sulbactam Treatment Modulates NMDA Receptor NR2B Subunit and Attenuates Neuroinflammation and Alcohol Intake in Male High Alcohol Drinking Rats

Ampicillin/Sulbactam Treatment Modulates NMDA Receptor NR2B Subunit and Attenuates Neuroinflammation and Alcohol Intake in Male High Alcohol Drinking Rats

Tau Exon 10 Inclusion by PrPC through Downregulating GSK3β Activity

Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery

Contact Info

Product

Resources

About