A paper on NAC and environmental enrichment in early psychosis and prevention efforts

Long, but includes both mouse and human research.

The aim of this study was to (1) compare the efficacy of NAC and/or EE provided during juvenile and/or adolescent periods for PVI/PNN impairments rescue in an SZ model, (2) understand the underlying mechanisms associated with the timely beneficial effects, and (3) explore in EP patients the effect of NAC on the described mechanisms.

We evaluated the short and long-term benefits of NAC and/or EE provided at different timing on PVI, following the early-life oxidative challenge. We found that NAC administration during the juvenile/peripubertal period, when followed by EE during the adolescence, prevents the long-term impairment of PVIs through inhibition of the MMP9/RAGE cascade.[59] NAC add-on treatment in EP patients also mitigates the MMP9/RAGE mechanism in association with increased prefrontal GABA levels and improvements of clinical symptoms and cognitive function.

Thus, NAC and EE may have similar or overlapping effects on pathological mechanisms mediated by oxidative stress and neuroinflammation, such as impairments of parvalbumin interneurons (PVI). Anomaly of PVI and their enwrapping perineuronal nets (PNN) is a hallmark of SZ[43–46]and contributes to abnormal high-frequency neuronal synchronization,[47][48] impacting multiple information processing critical for sensory perception and cognition, and possibly promoting hyperdopaminergia related to positive symptoms.[49–53] PVI are vulnerable to oxidative stress and inflammation, especially during their development.[54–58]A deleterious feedforward interaction between oxidative stress and neuroinflammation through MMP9/RAGE pathway during specific developmental periods appears to be central to PVI impairments.