Curcumin Potentiates α7 Nicotinic Acetylcholine Receptors and Alleviates Autistic-Like Social Deficits and Brain Oxidative Stress Status in Mice

Abstract

Autistic spectrum disorder (ASD) refers to a group of neurodevelopmental disorders characterized by impaired social interaction and cognitive deficit, restricted repetitive behaviors, altered immune responses, and imbalanced oxidative stress status. In recent years, there has been a growing interest in studying the role of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in the CNS. Influence of agonists for α7-nAChRs on the cognitive behavior, learning, and memory formation has been demonstrated in neuro-pathological condition such as ASD and attention-deficit hyperactivity disorder (ADHD). Curcumin (CUR), the active compound of the spice turmeric, has been shown to act as a positive allosteric modulator of α7-nAChRs. Here we hypothesize that CUR, acting through α7-nAChRs, influences the neuropathology of ASD. In patch clamp studies, fast inward currents activated by choline, a selective agonist of α7-nAChRs, were significantly potentiated by CUR. Moreover, choline induced enhancement of spontaneous inhibitory postsynaptic currents was markedly increased in the presence of CUR. Furthermore, CUR (25, 50, and 100 mg/kg, i.p.) ameliorated dose-dependent social deficits without affecting locomotor activity or anxiety-like behaviors of tested male Black and Tan BRachyury (BTBR) mice. In addition, CUR (50 and 100 mg/kg, i.p.) mitigated oxidative stress status by restoring the decreased levels of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and the cerebellum of treated mice. Collectively, the observed results indicate that CUR potentiates α7-nAChRs in native central nervous system neurons, mitigates disturbed oxidative stress, and alleviates ASD-like features in BTBR mice used as an idiopathic rodent model of ASD, and may represent a promising novel pharmacological strategy for ASD treatment.

An Update on the Exploratory Use of Curcumin in Neuropsychiatric Disorders

“…The first one, in which curcumin (20 mg/kg) was administered from PND 6 to 8, reported enhanced neural stem cell proliferation, along with increased sociability and improved short-term memory [ 102 ]. The second study evaluated three different doses of curcumin (25/50/100 mg/kg), showing restoration of different oxidative stress markers in the hippocampus and cerebellum, along with a dose-dependent increase in sociability in curcumin-treated mice [ 103 ].…”

Nano-Drug Design Based on the Physiological Properties of Glutathione

“…Based on the theory above, Ma et al [91] prepared Ag44(SR)30 silver nanoclusters with a ligand of 5-mercapto-2-nitrobenzoic acid, and completed the high precision detection of GSH, which enables more accurate and comprehensive diagnosis and assessment of Parkinson's disease. It had been reported that autism spectrum disorders (ASD) were also associated with GSH [92][93][94][95]. The research found that both reduced GSH and total GSH levels were lower in the ASD group than that in the control group [96].…”

Ameliorating potential of curcumin and its analogue in central nervous system disorders and related conditions: A review of molecular pathways

“…Additionally, curcumin at doses of 25, 50, and 100 mg/kg demonstrated improvement in social deficit among BTBR mice without affecting their anxiety‐like behavior and locomotor activity. At doses of 50 and 100 mg/kg, i.p., it also resulted in a marked decrease in oxidative stress by restoring decreased levels of antioxidant enzymes such as catalase and superoxide dismutase in the cerebellum and hippocampus of treated mice (Jayaprakash et al, 2021). Collectively, these findings demonstrate that curcumin potentiates α7‐nAChRs, attenuates oxidative stress, and alleviates ASD‐like characteristics in mice.…”