scholarly journals N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jose A. Morales-Garcia ◽  
Javier Calleja-Conde ◽  
Jose A. Lopez-Moreno ◽  
Sandra Alonso-Gil ◽  
Marina Sanz-SanCristobal ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Spatial Learning And Memory ◽  
South American ◽  
New Production ◽  
Sigma 1 Receptor ◽  
Neurogenic Niche ◽  
Sigma 1 ◽  
Functional Relevance

Abstract N,N-dimethyltryptamine (DMT) is a component of the ayahuasca brew traditionally used for ritual and therapeutic purposes across several South American countries. Here, we have examined, in vitro and vivo, the potential neurogenic effect of DMT. Our results demonstrate that DMT administration activates the main adult neurogenic niche, the subgranular zone of the dentate gyrus of the hippocampus, promoting newly generated neurons in the granular zone. Moreover, these mice performed better, compared to control non-treated animals, in memory tests, which suggest a functional relevance for the DMT-induced new production of neurons in the hippocampus. Interestingly, the neurogenic effect of DMT appears to involve signaling via sigma-1 receptor (S1R) activation since S1R antagonist blocked the neurogenic effect. Taken together, our results demonstrate that DMT treatment activates the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and improving spatial learning and memory tasks.

scholarly journals In vitro and in vivo sigma 1 receptor imaging studies in different disease states

2020 ◽  
Author(s):  
Hebaalla Agha ◽  
Christopher R. McCurdy
Keyword(s):  
Clinical Trials ◽  
Molecular Imaging ◽  
Receptor Imaging ◽  
Imaging Studies ◽  
Sigma 1 Receptor ◽  
The Road ◽  
Disease States ◽  
Sigma 1

Molecular imaging studies have paved the road for the development of successful σ1R ligands currently in clinical trials.

scholarly journals Synthesis and evaluation of sigma receptor ligands

2010 ◽  
Author(s):  
◽  
Kuo-Hsien Fan
Keyword(s):  
Sigma Receptor ◽  
Imaging Agents ◽  
Receptor Ligands ◽  
Receptor Ligand ◽  
Sigma 1 Receptor ◽  
Lead Compounds ◽  
In Vivo Distribution ◽  
Sigma 1

Sigma receptors are unique binding sites located in the central nervous system (CNS) and peripheral organs. Two sigma receptor subtypes ([signma]1 and [sigma]2) have been described so far. It is known that the [sigma]1 receptor is involved in a number of CNS disorders and the [sigma]2 receptor is involved in tumor proliferation among others. Because of the important biological functions of the [sigma] receptor, development of structure activity relationships (SAR) can aid in the identification of potential medications and imaging agents. Three series of analogs based on three lead compounds have been synthesized and evaluated for their in vitro affinity and selectivity for the [sigma]1 and [sigma]2 subtypes. Lead I is a selective [sigma]1 receptor ligand with anti-cocaine activity, but its in vivo distribution is unknown. Our in vitro binding results showed that all the Lead I analogs are potent [sigma]1 receptor ligands. Furthermore, one of the Lead I analogs was radioiodinated and evaluated for its in vivo distribution. In vivo evaluation of the radioiodinated Lead I analog has shown high brain uptake and specific binding to [sigma]1 receptor of the radioligand. Lead II is also a selective [sigma]1 receptor ligand and radioiodinated Lead II has been shown to be a potential imaging agent for the [sigma]1 receptor. Two of the Lead II analogs were shown to be potent [sigma]1 receptor ligands. The radioiodinated Lead II analogs were demonstrated to be potential imaging agents for [sigma]1 receptor in vivo. Lead III is one of the most selective [sigma]2 receptor ligands known to date. Only one of the newly synthesized Lead III analogs was found to be a selective [sigma]2 receptor ligand. The SAR study of Lead III analogs successfully indentified the important structural features in Lead III for [sigma]2 receptor binding. To summarize, the SAR studies based on the lead compounds have generated useful information and three potential [sigma]1 imaging agents were prepared in the studies.

scholarly journals Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 211 ◽  
Author(s):  
Maximilian Christ ◽  
Heike Huesmann ◽  
Heike Nagel ◽  
Andreas Kern ◽  
Christian Behl
Keyword(s):  
Clinical Investigation ◽  
Receptor Activation ◽  
Autophagic Flux ◽  
Neuroprotective Effects ◽  
Sigma 1 Receptor ◽  
C Elegans ◽  
Protein Clearance ◽  
Sigma 1

Dysfunction of autophagy and disturbed protein homeostasis are linked to the pathogenesis of human neurodegenerative diseases and the modulation of autophagy as the protein clearance process has become one key pharmacological target. Due to the role of sigma-1 receptors (Sig-1R) in learning and memory, and the described pleiotropic neuroprotective effects in various experimental paradigms, Sig-1R activation is recognized as one potential approach for prevention and therapy of neurodegeneration and, interestingly, in amyotrophic lateral sclerosis associated with mutated Sig-1R, autophagy is disturbed. Here we analyzed the effects of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73), a muscarinic receptor ligand and Sig-1R agonist, on autophagy and proteostasis. We describe, at the molecular level, for the first time, that pharmacological Sig-1R activation a) enhances the autophagic flux in human cells and in Caenorhabditis elegans and b) increases proteostasis capacity, ultimately ameliorating paralysis caused by protein aggregation in C. elegans. ANAVEX2-73 is already in clinical investigation for the treatment of Alzheimer’s disease, and the novel activities of this compound on autophagy and proteostasis described here may have consequences for the use and further development of the Sig-1R as a drug target in the future. Moreover, our study defines the Sig-1R as an upstream modulator of canonical autophagy, which may have further implications for various conditions with dysfunctional autophagy, besides neurodegeneration.

SA4503, a sigma-1 receptor agonist, suppresses motor neuron damage in in vitro and in vivo amyotrophic lateral sclerosis models

2014 ◽  
Vol 559 ◽  
pp. 174-178 ◽  
Author(s):  
Yoko Ono ◽  
Hirotaka Tanaka ◽  
Masafumi Takata ◽  
Yuki Nagahara ◽  
Yasuhiro Noda ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Receptor Agonist ◽  
Sigma 1 Receptor ◽  
Sigma 1 ◽  
Neuron Damage ◽  
Lateral Sclerosis

[123I]TPCNE: A novel SPET tracer for the sigma-1 receptor binds irreversibly in humans in vivo

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S655-S655
Author(s):  
James M Stone ◽  
Erik Arstad ◽  
Kjell Erlandsson ◽  
Rikki N Waterhouse ◽  
Peter J Ell ◽  
...  
Keyword(s):  
Sigma 1 Receptor ◽  
Sigma 1

In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Outcome ◽  
Neuroprotective Effect ◽  
Sirna Delivery ◽  
Repeated Administration ◽  
Spatial Learning And Memory ◽  
In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

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