An open-label, multicenter, controlled pharmaco-dynamic clinical trial to explore the Amyloid beta draining effect of Thiethylperazine (TEP) in subjects with early-to-mild dementia due to Alzheimer’s Disease in comparison to healthy volunteers - drainAD

Start Date27 May 2015

Sponsor / Collaborator

Immungenetics AG

100 Clinical Results associated with D1 receptor x D4 receptor x D2 receptor

100 Translational Medicine associated with D1 receptor x D4 receptor x D2 receptor

0 Patents (Medical) associated with D1 receptor x D4 receptor x D2 receptor

Literatures (Medical) associated with D1 receptor x D4 receptor x D2 receptor

01 Aug 2024·Neuroscience Letters

Sex differences in sensitivity to fentanyl effects in mice: Behavioral and molecular findings during late adolescence

Article

Author: Orso, Rodrigo ; Grassi-Oliveira, Rodrigo ; Kestering-Ferreira, Érika ; Gobira, Pedro Henrique ; Heberle, Bernardo Aguzzoli ; Sindermann Lumertz, Francisco ; Viola, Thiago Wendt

PURPOSESex differences play a crucial role in understanding vulnerability to opioid addiction, yet there have been limited preclinical investigations of this effect during the transition from adolescence to adulthood. The present study compared the behaviors of male and female rodents in response to fentanyl treatment and targeted molecular correlates in the striatum and medial prefrontal cortex.MATERIALS AND METHODSThirty adolescent C57BL/6J mice underwent a 1-week fentanyl treatment with an escalating dose. In addition to evaluating locomotor activity and anxiety-related parameters, we also assessed naloxone-induced fentanyl acute withdrawal jumps. We employed real-time quantitative PCR (qPCR) to assess overall gene expression of dopaminergic receptors (Drd1, Drd2, Drd4 and Drd5) and the μ-opioid receptor Oprm1. The levels of epigenetic base modifications including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were assessed on CpG islands of relevant genes.RESULTSFemales had higher locomotor activity than males after chronic fentanyl treatment, and they exhibited higher fentanyl withdrawal jumping behavior induced by naloxone. Females also presented lower Drd4 gene expression and DNA methylation (5mC + 5hmC) in the striatum. We found that locomotor activity and fentanyl withdrawal jumps were negatively correlated with Drd4 methylation and gene expression in the striatum, respectively.CONCLUSIONSThe findings suggested that female mice displayed heightened sensitivity to the effects of fentanyl treatment during the transition from adolescence to adulthood. This effect may be associated with molecular alterations related to the Drd4 gene.

01 Feb 2024·Progress in Neuro-Psychopharmacology and Biological Psychiatry

Behavioral, neurochemical and neuroimmune features of RasGEF1b deficient mice

Article

Author: Carvalho, Brener Cunha ; Vieira, Érica Leandro Marciano ; da Silva, Maria Carolina M ; Oliveira, Bruna da Silva ; Fernandes, Heliana de Barros ; de Brito Toscano, Eliana Cristina ; de Oliveira, Antônio Carlos Pinheiro ; Machado, Caroline Amaral ; de Miranda, Aline Silva ; Teixeira, Antônio Lúcio ; da Silva, Aristóbolo Mendes

The factor RasGEF1b is a Ras guanine exchange factor involved in immune responses. Studies have also implicated RasGEF1b in the CNS development. It is still limited the understanding of the role of RasGEF1b in CNS functioning. Using RasGEF1b deficient mice (RasGEF1b-cKO), we investigated the impact of this gene deletion in behavior, cognition, brain neurochemistry and microglia morphology. We showed that RasGEF1b-cKO mice display spontaneous hyperlocomotion and anhedonia. RasGEF1b-cKO mice also exhibited compulsive-like behavior that was restored after acute treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (5 mg/kg). A down-regulation of mRNA of dopamine receptor (Drd1, Drd2, Drd4 and Drd5) and serotonin receptor genes (5Htr1a, 5Htr1b and 5Htr1d) was observed in hippocampus of RasGEF1b-cKO mice. These mice also had reduction of Drd1 and Drd2 in prefrontal cortex and 5Htr1d in striatum. In addition, morphological alterations were observed in RasGEF1b deficient microglia along with decreased levels of hippocampal BDNF. We provided original evidence that the deletion of RasGEF1b leads to unique behavioral features, implicating this factor in CNS functioning.

01 Aug 2023·Molecular biology reports

Dopamine receptors gene overexpression in the microenvironment of invasive gastric cancer and its potential implications.

Article

Author: Ghaffari-Hamedani, Mohammad Mehdi ; Amjadi, Omolbanin ; Hedayatizadeh-Omran, Akbar ; Zaboli, Ehsan ; Janbabaei, Ghasem ; Ahangari, Ghasem

BACKGROUNDGastric cancer (GC) is the fifth most common cancer worldwide and the most commonly diagnosed cancer in Iran. The nervous system provides proximity to tumor cells by releasing neurotransmitters such as dopamine and presenting them to the corresponding receptor-bearing tumors. While nerve fibers infiltrate the tumor microenvironment, little is known about the expression levels of dopamine (DA), dopamine receptors (DRs), and catechol-O-methyltransferase (COMT) in GC patients.METHODSDRs and COMT expression were analyzed in 45 peripheral blood mononuclear cells (PBMCs) and 20 paired tumor and adjacent tissue of GC patients by quantitative polymerase chain reaction. DA was measured in plasma specimens using enzyme-linked immunosorbent assay. Protein-protein interaction analysis was carried out to identify GC-related hub genes.RESULTSIncreased expression of DRD1-DRD3 was found in tumor specimens compared with adjacent non-cancerous specimens (P < 0.05). A positive correlation was found between DRD1 and DRD3 expression (P = 0.009); DRD2 and DRD3 expression (P = 0.04). Plasma levels of dopamine were significantly lower in patients (1298 pg/ml) than in controls (4651 pg/ml). DRD1-DRD4 and COMT were up-regulated in PBMCs of patients compared with controls (P < 0.0001). Bioinformatic analyses showed 30 hub genes associated with Protein kinase A and extracellular signal-regulated kinase signaling pathways.CONCLUSIONSThe findings indicated dysregulation of DRs and COMT mRNA expression in GC and suggest that the brain- gastrointestinal axis may mediate gastric cancer development. Network analysis revealed that combination treatments could be considered for optimizing and improving the precision treatment of GC.

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