PUBLICATION
Behavioural, genomics and proteomic approach to examine Alzheimer's disease in zebrafish
- Authors
- Siddiqui, A., Abidin, S.A.Z., Shah, Z.A., Othman, I., Kumari, Y.
- ID
- ZDB-PUB-230427-54
- Date
- 2023
- Source
- Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 271: 109636 (Journal)
- Registered Authors
- Keywords
- Alzheimer's diseases, Neurodegeneration, Neuroinflammation, Okadaic acid, Zebrafish
- MeSH Terms
-
- Actins/metabolism
- Aged
- Alzheimer Disease*/drug therapy
- Alzheimer Disease*/genetics
- Alzheimer Disease*/metabolism
- Animals
- Brain/metabolism
- Disease Models, Animal
- Genomics
- Humans
- Okadaic Acid/adverse effects
- Okadaic Acid/metabolism
- Proteomics
- Zebrafish/metabolism
- PubMed
- 37100105 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Citation
Siddiqui, A., Abidin, S.A.Z., Shah, Z.A., Othman, I., Kumari, Y. (2023) Behavioural, genomics and proteomic approach to examine Alzheimer's disease in zebrafish. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 271:109636.
Abstract
Globally around 24 million elderly population are dealing with dementia, and this pathological characteristic is commonly seen in people suffering from Alzheimer's disease (AD). Despite having multiple treatment options that can mitigate AD symptoms, there is an imperative call to advance our understanding of the disease pathogenesis to unfold disease-modifying treatments/therapies. To explore the driving mechanisms of AD development, we stretch out further to study time-dependant changes after Okadaic acid (OKA)-induced AD-like conditions in zebrafish. We evaluated the pharmacodynamics of OKA at two-time points, i.e., after 4-days and 10-days exposure to zebrafish. T-Maze was utilized to observe the learning and cognitive behaviour, and inflammatory gene expressions such as 5-Lox, Gfap, Actin, APP, and Mapt were performed in zebrafish brains. To scoop everything out from the brain tissue, protein profiling was performed using LCMS/MS. Both time course OKA-induced AD models have shown significant memory impairment, as evident from T-Maze. Gene expression studies of both groups have reported an overexpression of 5-Lox, GFAP, Actin, APP, and OKA 10D group has shown remarkable upregulation of Mapt in zebrafish brains. In the case of protein expression, the heatmap suggested an important role of some common proteins identified in both groups, which can be explored further to investigate their mechanism in OKA-induced AD pathology. Presently, the preclinical models available to understand AD-like conditions are not completely understood. Hence, utilizing OKA in the zebrafish model can be of great importance in understanding the pathology of AD progression and as a screening tool for drug discovery.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping