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Amyloid beta (1-42) downregulates adenosine-2b receptors in addition to mitochondrial impairment and cholinergic dysfunction in memory-sensitive mouse brain regions.
- Source :
-
Journal of receptor and signal transduction research [J Recept Signal Transduct Res] 2020 Dec; Vol. 40 (6), pp. 531-540. Date of Electronic Publication: 2020 Jun 04. - Publication Year :
- 2020
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Abstract
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment. Adenosinergic receptors are considered as a potential alternative in the management of several neurodegenerative disorders. However, there is no information available on the role of A2b receptor in the pathophysiology of AD. Therefore, the effect of Aβ on the level of expression of A2b receptor was investigated in discrete memory-sensitive mouse brain regions. Aβ (1-42) was injected intracerebroventricularly to healthy male mouse to induce AD-like behavioral manifestations on Day-1 (D-1) of the experimental protocol. The animals were subjected to the Morris water maze (MWM) test on D-14 to D-18. On D-18, the animals were subjected to the Y-maze test after 30 min lag to the MWM paradigm. Aβ significantly attenuated the spatial working memory in MWM and Y-maze tests. In addition, Aβ significantly increased cholinergic dysfunction in terms of decrease in the activity of ChAT and ACh level and increase in the AChE activity in the hippocampus, pre-frontal cortex and amygdala of AD-like animals. Further, there was a significant increase in the extent of apoptosis in the selected mouse brain regions. Moreover, Aβ caused a substantial reduction in the mitochondrial function, integrity and bioenergetics in all the mouse brain regions. Furthermore, there was a significant decrease in the level of expression of A2b receptors in the selected brain regions of the rodents. Hence, it can be assumed that A2b receptor downregulation could be another therapeutic target in the management of AD.
- Subjects :
- Acetylcholine metabolism
Acetylcholinesterase
Alzheimer Disease chemically induced
Animals
Cognition Disorders etiology
Cognition Disorders metabolism
GPI-Linked Proteins antagonists & inhibitors
Male
Memory Disorders etiology
Memory Disorders metabolism
Mice
Mitochondria drug effects
Alzheimer Disease complications
Amyloid beta-Peptides toxicity
Cognition Disorders pathology
Memory Disorders pathology
Mitochondria pathology
Peptide Fragments toxicity
Receptor, Adenosine A2B chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1532-4281
- Volume :
- 40
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of receptor and signal transduction research
- Publication Type :
- Academic Journal
- Accession number :
- 32496898
- Full Text :
- https://doi.org/10.1080/10799893.2020.1767136