ABSTRACT
Drosophila melanogaster is a useful and highly tractable model organism for understanding the molecular mechanisms of human diseases. We previously characterized a new dUbqn knockdown model that induces learning-memory and locomotive deficits mediated by impaired proteostasis. Although proteinopathies are the main causes of neurodegenerative diseases, limited information is currently available on the relationship between proteostasis and neurodegenerative-related behavioral perturbations, such as locomotion, wakefulness, and sexual activities. Thus, the present study aimed to elucidate the mechanisms by which dUbqn depletion which is known to cause proteinopathies, affects neurodegenerative-related behavioral perturbations. Pan-neuronal dUbqn-depleted flies showed significantly reduced evening activity along with altered pre- and postsynaptic structural NMJ's proteins by attenuating signals of Bruchpilot puncta and GluRIIA clustering. In addition, the neurochemical profiles of GABA, glutamate, dopamine, and serotonin were disturbed and these changes also affected courtship behaviors in dUbqn-depleted flies. Collectively, these results extend our understanding on how dUbqn depletion affects neurochemical regulation to drive behavioral disturbances that are generally found in the early stage of neurodegenerative diseases. Moreover, the present study may contribute a novel finding to the design of new agents that prevent disease progression or even treat diseases related to neurodegeneration.
Subject(s)
Drosophila melanogaster/metabolism , Ubiquitin/deficiency , Animals , Courtship , Dopamine/metabolism , Dopamine/physiology , Drosophila melanogaster/physiology , Female , Gas Chromatography-Mass Spectrometry , Glutamic Acid/metabolism , Glutamic Acid/physiology , Larva , Male , Mass Spectrometry , Motor Activity/physiology , Nervous System/metabolism , Nervous System/physiopathology , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/physiopathology , Neuromuscular Junction/metabolism , Neuromuscular Junction/physiology , Serotonin/metabolism , Serotonin/physiology , Tandem Mass Spectrometry , Ubiquitin/metabolism , Ubiquitin/physiology , gamma-Aminobutyric Acid/metabolism , gamma-Aminobutyric Acid/physiologyABSTRACT
Asparaptine, an inhibitor of angiotensin-converting enzyme (ACE), is a newly discovered compound in asparagus. Asparaptine is a conjugate of arginine and asparagusic acid; this compound is suggested to be effective for preventing high blood pressure. For this reason, asparaptine has attracted remarkable attention in recent years, and it was therefore necessary to carry out further research. No studies to date have investigated the localization of asparaptine in asparagus. In this study, the localization of asparaptine in asparagus was clarified using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), a powerful method to visualize molecules.
Subject(s)
Asparagus Plant/metabolism , Disulfides/metabolism , Molecular Imaging/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Drosophila melanogaster is a model organism in neurodegenerative disease research. In neurodegenerative study, the direct spatial information of neurotransmitters such as γ-aminobutyric acid (GABA) in the brain of Drosophila melanogaster is important to understand the role of GABA. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is an attractive method for direct visualization of neurotransmitters. In this paper, we describe methods to visualize GABA in the brain and head of Drosophila melanogaster using MALDI-IMS.
