Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood. (2015)

An interesting research direction for ‘prophylactic psychiatry’:

Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood. (2015)

Oxidative 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 γ-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.

“Neurodevelopment during early adolescence is a key stage during maturation, with various structural, neurochemical, and molecular changes taking place in response to genetic and environmental cues. The formation of new neuronal connections during early adolescence also means a high level of vulnerability to pathologic insults ranging from stress to dietary deficiencies. The nutritional status during early adolescence has a great impact on the onset and severity of psychiatric diseases at adulthood. In the past decade, increasing interest in the potential benefits of early intervention for psychiatric diseases, such as schizophrenia, has been seen. Subjects at a high risk of developing psychosis exhibit cognitive impairments, compared with healthy subjects. Approximately one-third of subjects at a high risk develop psychosis within three years, and most are diagnosed as having schizophrenia. In this study, we found that the dietary intake of SFN-rich food during the juvenile and adolescence was capable of preventing PCP-induced cognitive deficits and oxidative stress at adulthood in mice. Although the precise mechanism underlying the preventive effect of SFN-rich food is currently unclear, the dietary intake of SFN-rich foods may be capable of regulating gene expression through epigenetic mechanisms. Since SFN has potent antioxidant and anti-inflammatory effects, SFN may prevent the onset of psychosis in subjects at a high risk and who exhibit oxidative stress and inflammation. Therefore, a randomized, double-blinded, placebo-controlled study of the dietary intake of SFN-rich foods in subjects at a high risk of psychosis is of great interest.”

“In the present study, we found that SFN exhibited prophylactic and therapeutic effects in a PCP-induced cognitive deficits model. Very recently, we found that supplementation with SFN-rich broccoli sprout extract for 8 weeks was effective for the treatment of cognitive impairment in medicated patients with schizophrenia, although other scores (such as psychotic symptoms) were not altered. Furthermore, a recent randomized, double-blinded, placebo-controlled study demonstrated that treatment with SFN-rich broccoli sprout extract significantly improved social interaction, abnormal behavior, and verbal communication in young men with autism spectrum disorder. Glucoraphanin (GF), a glucosinolate precursor of SFN, is widely consumed in cruciferous plant-rich diets; therefore, SFN is considered to have a low toxicity, and its administration in humans is well tolerated. It is reported that SFN readily crosses the blood-brain barrier of mouse after i.p. administration, suggesting that SFN in the brain can improve PCP-induced cognitive deficits. Together, these results suggest that SFN-rich broccoli sprout extract could have a potential therapeutic effect in patients with a number of psychiatric diseases including schizophrenia and autism spectrum disorder, since patients with these psychiatric diseases exhibit cognitive impairment”

As covered in Natural products for schizophrenia :

A small study found benefits from sulforaphane administration [1]: “Sulforaphane (SFN) is a molecule belonging to the isothiocyanate group of organosulfur compounds found in broccoli sprouts. It is known to have potent anti-oxidant and anti-inflammatory activity. Previously, we reported that SFN attenuated behavioral abnormalities in mice after administration of methamphetamine or phencyclidine, suggestive of a potential therapeutic potency in schizophrenia. Recently, we found that SFN improved cognitive deficits in phencyclidine-treated mice”.

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See also:

New Targets for Prevention of Schizophrenia: Is it Time for Interventions in the Premorbid Phase? (2015)

Stage specific and prophylactic treatments?

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