Dopamine transporter (SLC6A3) deficiency causes infantile Parkinson disease, for which there is no effective therapy. We have explored the effects of genetically deleting SLC6A3 in zebrafish. Unlike the wild-type, slc6a3-/- fish hover near the tank bottom, with a repetitive digging-like behavior. slc6a3-/- fish manifest pruning and cellular loss of particular tyrosine hydroxylase-immunoreactive neurons in the midbrain. Clozapine, an effective therapeutic for treatment-resistant schizophrenia, rescues the abnormal behavior of slc6a3-/- fish. Clozapine also reverses the abnormalities in the A8 region of the mutant midbrain. By RNA sequencing analysis, clozapine increases the expression of erythropoietin pathway genes. Transgenic over-expression of erythropoietin in neurons of slc6a3-/- fish partially rescues the mutant behavior, suggesting a potential mechanistic basis for clozapine's efficacy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642228 | PMC |
| http://dx.doi.org/10.1016/j.isci.2019.06.039 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Neural mechanisms of mutualistic fish cleaning behaviour: a study in the wild.
Biol Lett
October 2024
Swire Institute of Marine Science, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, People's Republic of China.
Article Synopsis
- Cleaner fish play a vital role in coral reef ecosystems by removing ectoparasites from other fish, known as clients, highlighting the importance of mutualistic relationships in marine communities.
- A study conducted in New Caledonia identified 233 genes that are activated in cleaner fish when interacting with clients, revealing new insights into the neural mechanisms behind their cleaning behavior.
- Key findings included the involvement of neurotransmitters and immediate early genes related to learning and memory, with a novel discovery of neuropeptide Y influencing feeding behavior in these interactions.
Biochemical and molecular responses to long-term salinity challenges in northern quahogs Mercenaria mercenaria.
Fish Shellfish Immunol
November 2024
School of Forest, Fisheries, and Geomatics Sciences, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, 32653, USA. Electronic address:
Article Synopsis
- Salinity is crucial for the survival and performance of aquatic organisms, particularly for species like the northern quahog, which is significant in US coastal aquaculture.
- The study aimed to assess how northern quahogs respond at cellular and molecular levels to long-term salinity changes, including effects on survival, hemocyte function, amino acid concentrations, and gene expression.
- Results indicated that quahogs survived well under varying salinity levels, showed significant changes in immune functions and amino acid concentrations correlated with salinity, and exhibited distinct gene expressions linked to salinity stress.
Long-term exposure to ionic liquid [Cmim]Br induces the potential risk of anxiety and memory deterioration through disturbing neurotransmitter systems.
Neurotoxicology
September 2024
College of Environmental Science and Engineering, State Environmental Protection Engineering Center for Pollution Treatment and Control in Textile Industry, Donghua University, Shanghai 201620, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address:
1-octyl-3-methylimidazolium bromide ([Cmim]Br), one of the ionic liquids (ILs), has been used in various fields as an alternative green solvent of conventional organic solvents. Increased application and stabilization of imidazole ring structure lead to its release into the aquatic environment and long-term retention. Structure-activity relationship consideration suggested that ILs may be acetylcholinesterase inhibitors; however, neurotoxicity in vivo, especially the underlying mechanisms is rarely studied.
View Article and Find Full Text PDFParental exposure to antidepressants has lasting effects on offspring? A case study with zebrafish.
Chemosphere
May 2024
Centre for Environmental and Marine Studies (CESAM), Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal. Electronic address:
Article Synopsis
- Fish share similar neurotransmitter pathways with humans, making them vulnerable to the effects of drugs like fluoxetine, which can lead to physiological changes.
- Study findings on zebrafish indicate that parental exposure to fluoxetine alters offspring development, causing issues such as early hatching, malformations, and behavioral impairments.
- The observed changes, including altered gene expression and neurotransmitter levels, suggest potential long-term effects that could influence multiple generations, highlighting the need for more research in this area.
The influence of acute dopamine transporter inhibition on manic-, depressive-like phenotypes, and brain oxidative status in adult zebrafish.
Prog Neuropsychopharmacol Biol Psychiatry
April 2024
Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS, Brazil; The International Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA 70458, USA. Electronic address:
Functional changes in dopamine transporter (DAT) are related to various psychiatric conditions, including bipolar disorder (BD) symptoms. In experimental research, the inhibition of DAT induces behavioral alterations that recapitulate symptoms found in BD patients, including mania and depressive mood. Thus, developing novel animal models that mimic BD-related conditions by pharmacologically modulating the dopaminergic signaling is relevant.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!