Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth, 6021, South Africa. Electronic address:
Published: January 2023
AI Article Synopsis
Article Abstract
The neurotoxic, non-proteinogenic amino acid β-N-methylamino-l-alanine (BMAA) has been implicated in the development of neurodegenerative diseases; however, the mechanism(s) and mode(s) of toxicity remain unclear. Similarities in the neuropathology and behavioural deficits of neonatal rats exposed to either BMAA or reserpine, a known vesicular monoamine transporter 2 (VMAT2) inhibitor, suggest a similar mode of action. The aims of this study were therefore to determine if BMAA could prevent the uptake of serotonin into dense granules via inhibition of VMAT2, and, if so, the type of inhibition caused by BMAA. Exposing platelet dense granules to BMAA resulted in a concentration-dependent reduction in serotonin uptake. The inhibition of VMAT2 was non-competitive. The findings from this study support previous reports that BMAA-associated neuropathologies in a neonatal rat model may be due to VMAT2 inhibition during critical periods of neurogenesis.
Background: Apathy is a syndrome of decreased goal-directed activity, one of the main features of different brain disorders. Despite its high prevalence and life-threatening potential, there are currently very few options for its pharmacological treatment, which may be related to the lack of valid animal models.
Aims: The vesicular monoamine transporter 2 inhibitor tetrabenazine (TBZ) was used in this study to model apathy-related behavior in pathologies linked to a depletion of dopamine.
The quantitative analysis of vesicular neurotransmitters in neurons in situ is paramount for investigating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease (PD). Unfortunately, a direct approach for monitoring neurotransmitter chemistry in single vesicles in fresh brain tissue has remained inaccessible so far. Here, we introduce an innovative platform of single-vesicle electrochemistry (SVE) in fresh brain tissue, enabling the quantification of neurotransmitters at the single-vesicle level for both soma and varicosity.
Vesicular monoamine transporter 2 inhibitors (VMAT2i) are currently Food and Drug Administration-approved for the treatment of Huntington disease chorea and tardive dyskinesia. Additionally, they are often used for other hyperkinetic movement disorders in clinical practice. Due to a lack of head-to-head clinical trials, management of VMAT2i in the clinical setting may be unclear and rely on the clinical experience of the practitioner.
We aimed to examine the relationship of Dopamine transporter (DAT) and vesicular monoamine transporter (VMAT-2) gene and protein levels with psychic experiences and other clinical parameters in individuals with Methamphetamine Use Disorder (MUD). This study included 50 males diagnosed with MUD and 50 males as a smoking control (SC) and nonsmoking control (NSC). Community Assessment of Psychic Experiences (CAPE) was administered to patients and controls; Addiction Profile Index, Treatment Motivation Questionnaire, and Substance Craving Scale were administered only to the patient group.
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA.
In recent years, methamphetamine (METH) misuse in the US has been rapidly increasing, and there is no FDA-approved pharmacotherapy for METH use disorder (MUD). In addition to being dependent on the drug, people with MUD develop a variety of neurological problems related to the toxicity of this drug. A variety of molecular mechanisms underlying METH neurotoxicity has been identified, including the dysfunction of the neuroprotective protein parkin.
