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

Abstract

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.

Prophylactic effects of sulforaphane on depression-like behavior and dendritic changes in mice after inflammation

“…Subsequently, we also reported that dietary intake of SFN-rich broccoli sprout extracts during juvenile and adolescence can prevent PCP-induced cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the prefrontal cortex (PFC) at adulthood [30,31]. These finding suggest that SFN could be a potential prophylactic natural compound for neuropsychiatric diseases [29][30][31].…”

“…LPS and SFN were administered intraperitoneally (ip) into mice. The doses of LPS (0.5 mg/kg) and SFN were selected by previous reports [10][11][12][13][29][30][31]]. …”

“…2.3 mmol GF per 1 kg-diet), the extract powder was mixed with a basal diet CE-2 (CLEA Japan Inc., Tokyo, Japan) and then pelletized at a processing facility (Oriental Yeast Co., ltd., Tokyo, Japan). The GF content in the diet was determined by high-performance liquid chromatography as previously described [31].…”

“…We previously reported that SFN showed antiinflammatory and antioxidative effects in methamphetamine (or PCP)-induced behavioral abnormalities in mice thorough antiinflammatory and antioxidant activities [29][30][31]. Therefore, the present study was undertaken to examine whether SFN or dietary intake of glucoraphanin (GF) (a glucosinolate precursor of SFN) food can prevent the onset of depressionlike behaviors in mice after inflammation.…”

Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats

“…Previous study reported that dietary intake of sulforaphane-rich broccoli sprout extracts during juvenile and adolescence prevented phencyclidine-induced cognitive deficits [16]. That indicated the pharmacological activity of SFN in recovery of memory impairment.…”