Frontiers in cellular neuroscience
January 1, 2022
Charles Sutton, Erin Q Williams, Hoomam Homsi et al.
13 citations
Mutations in the dopamine transporter gene cause Dopamine Transporter Deficiency Syndrome (DTDS), a fatal infantile parkinsonism-dystonia with no current treatment. Pharmacological chaperones can rescue some disease-causing variants. This study examined structure-activity relationships for two known chaperones, bupropion and ibogaine. The isoquinuclidine substituent of ibogaine and its analogs is important for chaperone efficacy. For bupropion, the secondary amine group is essential. Additional analogs with varying chemical modifications showed variable chaperone efficacies, contributing to the design of improved dopamine transporter pharmacological chaperones.
Frontiers in cellular neuroscience
January 1, 2023
Cristina Delgado-Sallent, Thomas Gener, Pau Nebot et al.
Blocking NMDA receptors with phencyclidine (PCP) in mice impairs short-term and long-term object recognition memory and disrupts auditory processing, modeling cognitive deficits in schizophrenia. Memory impairments were linked to increased theta oscillations in the medial prefrontal cortex, decreased gamma oscillations and theta-gamma coupling in the dorsal hippocampus, and disrupted communication between the two regions. The atypical antipsychotic risperidone, given daily for two weeks after PCP, rescued memory deficits and partly normalized hippocampal activity but did not fully restore prefrontal cortex or circuit connectivity. Auditory processing deficits were also partially reversed. The findings suggest that NMDA receptor hypofunction disconnects prefrontal-hippocampal circuits, and risperidone may improve cognition by acting on this circuitry.
Frontiers in cellular neuroscience
January 1, 2018
Farah Chamaa, Hisham F Bahmad, Ahmad-Kareem Makkawi et al.
Sub-anesthetic doses of nitrous oxide (N2O), an NMDA antagonist, increase hippocampal cell proliferation in adult male rats. Single exposure to 70% N2O with 30% oxygen led to a 1.4-fold increase in cell proliferation in the dentate gyrus after seven days compared to sham groups, while multiple exposures doubled the rate. Cell proliferation rates were comparable between N2O and sham groups at day one. The findings suggest that N2O, like ketamine, may ultimately enhance neurogenesis, pointing to potential antidepressant effects.