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Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
Another highly toxic compound which is specific to catecholaminergic neurons is 6-hydroxydopamine (6-OHDA), also known as oxidopamine [53]. It is a synthetic compound used by researchers to selectively destroy dopaminergic and noradrenergic neurons in the brain. 6-OHDA is structurally similar to DA and NE and has high affinity for their transporters, DAT and NET, respectively. Administration of selective noradrenaline reuptake inhibitors, such as dismethylimipramine or imipramine, before 6-OHDA protects the noradrenergic neurons from damage in these animals and selectively destroys dopaminergic neurons. Because 6-OHDA does not cross the BBB, it is injected directly into the substantia nigra pars compacta, medial forebrain bundle (MFB), which consists of efferent fibers from nigral neuronal cell bodies to the striatum, or into the striatum, where it specifically kills DA and NE neurons.
Understanding host responses to equine encephalitis virus infection: implications for therapeutic development
Published in Expert Review of Anti-infective Therapy, 2022
Kylene Kehn-Hall, Steven B. Bradfute
Acriflavine suppressed VEEV TC-83, VEEV TrD, EEEV, WEEV, WNV, but not VSV replication. Acriflavine is typically used as an antiseptic, but more recently was shown to inhibit Ago2, a protein involved in miRNA processing [144]. The importance of Ago2 for alphavirus replication was further shown through MEFs lacking Ago2 having decreased VEEV TC-83 viral RNA levels, structural protein production, and infectious titers [141]. In addition, multiple inhibitors of the miRNA machinery, including aurintricarboxylic acid (ATA), oxidopamine hydrochloride (OXD) and suramin (SUR), acriflavine, and poly L lysine, suppressed VEEV TC-83 replication, with acriflavine being the most potent. Acriflavine partially protected C3H/HeN mice from VEEV TC-83 infection, but did not have a protective effect on BALB/c mice infected with VEEV TrD, indicating that inhibition of Ago2 alone is not sufficient to protect mice from a fully virulent VEEV infection.
Neuroprotective effects of catechins in an experimental Parkinson’s disease model and SK-N-AS cells: evaluation of cell viability, anti-inflammatory and anti-apoptotic effects
Published in Neurological Research, 2022
Gülşen Özduran, Eda Becer, Hafize Seda Vatansever, Sevinç Yücecan
Neurotoxin compounds such as 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) are widely used to establish models of PD both in vivo and in vitro. 6-OHDA, also known as oxidopamine, is a toxic oxidative metabolite with a chemical structure similar to catecholamines (especially dopamine and norepinephrine) and can poorly cross the blood-brain barrier. 6-OHDA has a high affinity for dopaminergic neurons of SNpc. Thus, it induces oxidative stress, neuroinflammation, apoptosis and neurodegeneration processes in the nigrostriatal system and allows the development of PD models [6,7]. The mechanisms of action of 6-OHDA can be explained as follows: initially, intracellular and extracellular autoxidation of OHDA increases the production of ROS such as hydrogen peroxide (H2O2), superoxide radical (•O2–), and hydroxyl radical (•OH–). Then, increased in ROS levels cause oxidative stress, lipid peroxidation, biomembrane and protein damage, and damage to ribonucleic acid and deoxyribonucleic acid. Mitochondria, which is responsible for cell viability, is also affected. When exposed to increased ROS levels and oxidative stress, deterioration of mitochondrial Ca2+ homeostasis, an increase in cytoplasmic-free calcium level, a reduction in mitochondrial respiratory-chain complex I and IV activity, increased permeability of mitochondrial membrane and mitochondrial dysfunction are observed. In that case, caspase 3-dependent apoptotic mechanisms are induced in neurons. Neuronal cell loss increases with the occurrence of apoptosis [6–8].