1IDrugs 2009 Dec 12: 734-7
TitleSociety for Neuroscience - 39th Annual Meeting. Part 2 - Novel therapies for neurodegenerative disorders and other CNS diseases.
AbstractThe 39th Annual Meeting of the Society for Neuroscience (SFN), held in Chicago, included topics covering new therapeutic developments in the field of neuroscience. This conference report highlights selected presentations on novel neuroprotective and antiparkinsonian agents, and compounds in development for the treatment of dementia, schizophrenia, depression, obesity and spinal muscular atrophy. Investigational drugs discussed include velusetrag and TD-8954 (both from Theravance Inc), SEP-228791 and SEP-226330 (both from Sepracor Inc), ADL-5510 (Adolor Corp), PF-217830 (Pfizer Inc), KB-099520 (Karo Bio AB), tesofensine (NeuroSearch A/S) and TRP6-01 (Theraptosis).
SCZ Keywordsschizophrenia
2Clin Psychopharmacol Neurosci 2012 Aug 10: 94-8
TitleEffects of the antioxidant sulforaphane on hyperlocomotion and prepulse inhibition deficits in mice after phencyclidine administration.
AbstractAccumulating evidence suggests that oxidative stress plays a role in the pathophysiology of schizophrenia and that the potent antioxidants may be potential therapeutic drugs for schizophrenia. This study was undertaken to examine the effects of the potent antioxidant sulforaphane (SFN), found in cruciferous vegetables, on behavioral abnormalities (e.g., hyperlocomotion and prepulse inhibition [PPI] deficits) in mice after a single administration of the N-methyl-D-aspartate (NMDA)-receptor antagonist phencyclidine (PCP).
Effects of SFN (3, 10, and 30 mg/kg, intraperitoneally [i.p.]) on hyperlocomotion and PPI deficits in the adult male ddY mice after administration of PCP (3.0 mg/kg, subcutaneously [s.c.]) were examined.
Administration of SFN (30 mg/kg, intraperitoneally [i.p.]), but not low doses (3 and 10 mg/kg, i.p.), significantly attenuated hyperlocomotion in mice after PCP administration (3.0 mg/kg, subcutaneously [s.c.]). Furthermore, administration of SFN (3, 10, and 30 mg/kg, i.p.) attenuated the PPI deficits in mice after PCP administration (3.0 mg/kg, s.c.) in a dose-dependent manner.
These results suggest that SFN has antipsychotic activity in an animal model of schizophrenia. Therefore, it is likely that SFN may be a potential therapeutic drug for schizophrenia.
SCZ Keywordsschizophrenia
3PLoS ONE 2015 -1 10: e0127244
TitleDietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood.
AbstractOxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory ?-aminobutyric acid (GABA) neurons expressing parvalbumin (PV), which is also involved in cognitive impairment. Sulforaphane (SFN), an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP). Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN) during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed) in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.
SCZ Keywordsschizophrenia
4Clin Psychopharmacol Neurosci 2015 Apr 13: 62-7
TitleAn Open Study of Sulforaphane-rich Broccoli Sprout Extract in Patients with Schizophrenia.
Abstractschizophrenia is a mental disorder characterized by severe cognitive impairment. Accumulating evidence suggests a role for oxidative stress in the pathophysiology of schizophrenia. Sulforaphane (SFN) extracted from broccoli sprout is an agent with potent anti-oxidant and anti-inflammatory activity. In this study, we attempted to evaluate the effect of SFN on cognitive impairment in medicated patients with schizophrenia.
We recruited a total of 10 outpatients with schizophrenia, all of whom gave informed consent. Participants took 3 tablets of SFN, consisting of 30 mg of SFN-glucosinolate per day, for 8 weeks. Clinical symptoms using the Positive and Negative Syndrome Scale (PANSS) and cognitive function using the Japanese version of CogState battery were evaluated at the beginning of the study and at week 8.
A total of 7 patients completed the trial. The mean score in the Accuracy component of the One Card Learning Task increased significantly after the trial. However, we detected no other significant changes in participants.
This result suggests that SFN has the potential to improve cognitive function in patients with schizophrenia.
SCZ Keywordsschizophrenia