Effects and mechanism of action of isatin, a MAO inhibitor, on in vivo striatal dopamine release

Justo, Lorenzo; Durán, R.; Alfonso, Miguel Ángel Martínez; Fajardo, Daniel; Faro, L.R.F.

doi:10.1016/j.neuint.2016.06.012

Cited by 25 publications

(26 citation statements)

References 65 publications

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“…The dopamine neuronal network is related to an age-related decline in cognitive performance and executive function, and the dopamine precursor levodopa has been shown to improve the task-based learning rate and task performance in the elderly [14]. It has also been reported that MAO-B inhibitors improve cognitive function in rodents [15,16,17]. MAO-B is an enzyme for dopamine metabolism and thus decreases dopamine levels in the brain [18].…”

Section: Discussionmentioning

confidence: 99%

Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System

et al. 2019

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Tryptophan-tyrosine (WY)-related peptides including the β-lactopeptide of the glycine-threonine-tryptophan-tyrosine peptide, β-lactolin, improve spatial memory. However, whether and how the WY dipeptide as the core sequence in WY-related peptides improves memory functions has not been investigated. This study assessed the pharmacological effects of the WY dipeptide on memory impairment to elucidate the mechanisms. Here, we showed that oral administration of dipeptides of WY, tryptophan-methionine (WM), tryptophan-valine, tryptophan-leucine, and tryptophan-phenylalanine improved spontaneous alternation of the Y-maze test in scopolamine-induced amnesic mice. In contrast, tyrosine-tryptophan, methionine-tryptophan, tryptophan, tyrosine, and methionine had no effect. These results indicated that the conformation of dipeptides with N-terminal tryptophan is required for their memory improving effects. WY dipeptide inhibited the monoamine oxidase B activity in vitro and increased dopamine levels in the hippocampus and frontal cortex, whereas tryptophan did not cause these effects. In addition, the treatment with SCH-23390, a dopamine D1-like receptor antagonist, and the knockdown of the hippocampal dopamine D1 receptor partially attenuated the memory improvement induced by the WY dipeptide. Importantly, WY dipeptide improved the spontaneous alternations of the Y-maze test in aged mice. These results suggest that the WY dipeptide restores memory impairments by augmenting dopaminergic activity. The development of supplements rich in these peptides might help to prevent age-related cognitive decline.

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Section: Discussionmentioning

confidence: 99%

Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System

et al. 2019

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“…As β-lactolin is effectively distributed in the hippocampus 1 h after oral administration, MAO-B inhibition may be involved in the β-lactolin-induced increase of the extracellular dopamine in the hippocampus. It has been reported previously that MAO-B inhibitors enhance cognition in rodents [16,17,18]. In fact, lacto-peptides containing the WY sequence, such as β-lactolin, have been found to improve memory in a scopolamine-induced mouse model of amnesia, in addition to healthy young-adult and aged mice [7].…”

Section: Discussionmentioning

confidence: 99%

The Lacto-Tetrapeptide Gly–Thr–Trp–Tyr, β-Lactolin, Improves Spatial Memory Functions via Dopamine Release and D1 Receptor Activation in the Hippocampus

et al. 2019

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Scope: Peptides containing tryptophan–tyrosine sequences, including the lacto-tetrapeptide glycine–threonine–tryptophan–tyrosine (GTWY) and β-lactolin, from β-lactoglobulin in whey enzymatic digestion, enhance hippocampus-dependent memory functions, which are blocked by the systemic administration of dopamine D1-like antagonist. In this study, we investigated the role of the hippocampal dopaminergic system in the memory-enhancing effect of β-lactolin. Methods and Results: The results of in vivo microdialysis revealed that oral administration of β-lactolin increased the extracellular concentration of dopamine in the hippocampus and enhanced both spatial working memory, as measured in the Y-maze test, and spatial reference memory, as measured in the novel object location test. These memory-enhancing effects of β-lactolin, but not the baseline memory functions, were impaired by the knockdown of the dopamine D1 receptor subtype in the hippocampus. β-Lactolin also enhanced object memory, as measured by the novel object recognition test. However, D1 knockdown in the hippocampus spared this memory function either with or without the administration of β-lactolin. Conclusions: The present results indicate that oral administration of β-lactolin increases dopamine release and D1 receptor signaling in the hippocampus, thereby enhancing spatial memory, but it may improve object memory via a separate mechanism.

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“…Involvement of functional inhibition of MAO B in the neuroprotective effect of isatin in animal models of parkinsonism is also supported by the fact that isatin prevents the loss of striatal dopamine . In this context, it is especially interesting that intrastriatal administration of isatin to rats significantly increases extracellular striatal dopamine .…”

Section: Isatin As a Neuroprotectormentioning

confidence: 94%

“…In this context, it is especially interesting that intrastriatal administration of isatin to rats significantly increases extracellular striatal dopamine [102]. However, besides evident inhibition of MAO B-dependent biotransformation of MPTP, the neuroprotective dose of isatin significantly influences the repertoire of brain proteins bound to the ubiquitin receptor, the 19S proteasomal Rpn10 subunit, which is considered as ubiquitin receptor responsible for delivery of ubiquitinated proteins to the proteasome proteolytic machinery [17].…”

Section: Tablementioning

confidence: 99%

Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications

et al. 2018

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Isatin (indole-2,3-dione) is an oxidized indole. It is widely distributed in mammalian tissues and body fluids, where isatin concentrations vary significantly from <0.1 to > 10 µM. Isatin output is increased under conditions of stress. Exogenously administered isatin is characterized by low toxicity, mutagenicity, and genotoxicity in vivo. Cytotoxic effects of isatin on various cell cultures are usually observed at concentrations exceeding 100 µM. Binding of [ H]isatin to rat brain sections is consistent with its physiological concentrations. Proteomic analysis of mouse and rat brain isatin-binding proteins revealed about 90 individual proteins, which demonstrated significant interspecies differences (rat versus mouse). Certain evidence exist that redox state(s) and possibly other types of posttranslational modifications regulate affinity of target proteins to isatin. Recent data suggest that interacting with numerous intracellular isatin binding proteins, isatin can act as a regulator of complex protein networks in norm and pathology. Physiological concentrations of isatin in vitro inhibit monoamine oxidase B and natriuretic peptide receptor guanylate cyclase, higher (neuroprotective) concentrations (50-400 μM) cause apoptosis of various (including malignant tumor) cell lines and influence expression of certain apoptosis-related genes. Being administered in vivo, isatin exhibits various behavioral effects; it attenuates manifestations of MPTP-induced parkinsonism and tumor growth in experimental animal models. © 2017 BioFactors, 44(2):95-108, 2018.

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Effects and mechanism of action of isatin, a MAO inhibitor, on in vivo striatal dopamine release

Cited by 25 publications

References 65 publications

Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System

Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System

The Lacto-Tetrapeptide Gly–Thr–Trp–Tyr, β-Lactolin, Improves Spatial Memory Functions via Dopamine Release and D1 Receptor Activation in the Hippocampus

Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications

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