Nauclea officinalis extract rescues working memory deficits in adolescent maternal immune activation offspring by restoring cholinergic sign

Maternal immune activation (MIA) serves as a significant environmental risk factor for the development of schizophrenia-associated cognitive impairments. These deficits are mechanistically associated with dysfunction within the prefrontal cortex, particularly regarding cholinergic neurotransmission. Understanding how natural compounds might modulate this specific pathway is relevant for metabolic and neurodevelopmental research contexts.

Researchers utilized a poly (I:C)-induced MIA rat model to investigate the effects of Nauclea officinalis extract (NOE). Adolescent offspring from these models were administered NOE at doses of 5, 10, and 20 mg/kg. The study employed behavioral assessments, in vivo electrophysiology, and molecular assays to evaluate neuronal activity and inflammatory markers within the infralimbic medial prefrontal cortex (IL-mPFC).

The primary findings indicate that NOE treatment dose-dependently attenuated MIA-induced neuroinflammation, specifically reducing levels of IL-1β, IL-6, and TNF-α. Furthermore, the extract restored acetylcholine levels while reducing acetylcholinesterase activity without altering M1 or M3 receptor expression. Behavioral testing revealed that NOE (20 mg/kg) significantly improved 30-second delay working memory performance. This cognitive improvement was blocked by the muscarinic receptor antagonist scopolamine and mimicked by the AChE inhibitor physostigmine.

Electrophysiological data demonstrated that NOE rescued MIA-impaired long-term potentiation (LTP) and paired-pulse ratio (PPR), while enhancing delay-related firing of IL pyramidal neurons. These restorative effects were replicated by physostigmine and antagonized by scopolamine, confirming the involvement of cholinergic transmission. The authors conclude that NOE alleviates MIA-induced working memory deficits by reducing neuroinflammation and functionally potentiating cholinergic signaling in the IL-mPFC.

While these results position NOE as a promising multi-target agent for cognitive impairments in neurodevelopmental disorders, the study is limited to rodent models. The findings highlight the IL cholinergic system as a critical therapeutic target but do not provide clinical recommendations or dosages for human application. This research serves as a laboratory reference for understanding metabolic and neuroprotective mechanisms rather than medical advice.