PUBLICATION
Modulation of adenosine signaling reverses 3-nitropropionic acid-induced bradykinesia and memory impairment in adult zebrafish
- Authors
- Wiprich, M.T., Altenhofen, S., Gusso, D., da Rosa Vasques, R., Zanandrea, R., Kist, L.W., Bogo, M.R., Bonan, C.D.
- ID
- ZDB-PUB-220720-5
- Date
- 2022
- Source
- Progress in neuro-psychopharmacology & biological psychiatry 119: 110602 (Journal)
- Registered Authors
- Bonan, Carla Denise
- Keywords
- 3-nitropropionic acid, Huntington's disease, Memory, A(2)A receptors antagonist, Motor dysfunction, Zebrafish
- MeSH Terms
-
- Adenosine/pharmacology
- Animals
- Caffeine*/pharmacology
- Dipyridamole/pharmacology
- Dopamine
- Hypokinesia
- Nitro Compounds
- Propionates
- Receptor, Adenosine A2A/genetics
- Zebrafish*
- PubMed
- 35843370 Full text @ Prog. Neuropsychopharmacol. Biol. Psychiatry
Citation
Wiprich, M.T., Altenhofen, S., Gusso, D., da Rosa Vasques, R., Zanandrea, R., Kist, L.W., Bogo, M.R., Bonan, C.D. (2022) Modulation of adenosine signaling reverses 3-nitropropionic acid-induced bradykinesia and memory impairment in adult zebrafish. Progress in neuro-psychopharmacology & biological psychiatry. 119:110602.
Abstract
Huntington's disease (HD) is a neurodegenerative disorder, characterized by motor dysfunction, psychiatric disturbance, and cognitive decline. In the early stage of HD, occurs a decrease in dopamine D2 receptors and adenosine A2A receptors (A2AR), while in the late stage also occurs a decrease in dopamine D1 receptors and adenosine A1 receptors (A1R). Adenosine exhibits neuromodulatory and neuroprotective effects in the brain and is involved in motor control and memory function. 3-Nitropropionic acid (3-NPA), a toxin derived from plants and fungi, may reproduce HD behavioral phenotypes and biochemical characteristics. This study investigated the effects of acute exposure to CPA (A1R agonist), CGS 21680 (A2AR agonist), caffeine (non-selective of A1R and A2AR antagonist), ZM 241385 (A2AR antagonist), DPCPX (A1R antagonist), dipyridamole (inhibitor of nucleoside transporters) and EHNA (inhibitor of adenosine deaminase) in an HD pharmacological model induced by 3-NPA in adult zebrafish. CPA, CGS 21680, caffeine, ZM 241385, DPCPX, dipyridamole, and EHNA were acutely administered via i.p. in zebrafish after 3-NPA (at dose 60 mg/kg) chronic treatment. Caffeine and ZM 241385 reversed the bradykinesia induced by 3-NPA, while CGS 21680 potentiated the bradykinesia caused by 3-NPA. Moreover, CPA, caffeine, ZM 241385, DPCPX, dipyridamole, and EHNA reversed the 3-NPA-induced memory impairment. Together, these data support the hypothesis that A2AR antagonists have an essential role in modulating locomotor function, whereas the activation of A1R and blockade of A2AR and A1R and modulation of adenosine levels may reduce the memory impairment, which could be a potential pharmacological strategy against late-stage symptoms HD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping