curcumin and Autism-Spectrum-Disorder

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.

Topics: Allosteric Regulation; alpha7 Nicotinic Acetylcholine Receptor; Animals; Autism Spectrum Disorder; Autistic Disorder; Choline; Curcumin; Disease Models, Animal; Hippocampus; Male; Mice; Mice, Inbred C57BL; Neurons; Nicotinic Agonists; Oxidative Stress; Social Behavior

Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders characterized by deficits in social communication and interaction, repetitive stereotyped behaviors, and cognitive impairments. Curcumin has been indicated to be neuroprotective against neurological and psychological disorders. However, the role of curcumin in autistic phenotypes remains unclear.. C57BL/6J (C57) and BTBR mouse pups were treated with 0.1% dimethyl sulfoxide (DMSO) or curcumin (20 mg/kg) from postnatal day 6 (P6) to P8. Neural progenitor cells (NPCs) in the hippocampal dentate gyrus (DG) were evaluated on P8, and neurogenesis was measured on P24 by immunofluorescence. A battery of behavioral tests was carried out when the mice were 8 weeks of age.. Neonatal curcumin treatment improved autism-related symptoms in BTBR mice, enhancing sociability, reducing repetitive behaviors, and ameliorating cognitive impairments. Furthermore, the suppression of hippocampal neurogenesis in BTBR mice was greatly rescued after neonatal curcumin treatment, leading to an increase in neurogenic processes and an increase in NPC proliferation concomitant with an expansion of the NPC pool on P8, and NPC differentiation towards the neuronal lineage was promoted in the DG of BTBR mice on P24.. Our findings suggest that neonatal curcumin treatment elicits a therapeutic response through the restoration of hippocampal neurogenesis in BTBR mice and thus may represent a promising novel pharmacological strategy for ASD treatment.

Topics: Animals; Animals, Newborn; Autism Spectrum Disorder; Behavior, Animal; Cell Proliferation; Curcumin; Dentate Gyrus; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Neural Stem Cells; Neurogenesis; Neuroprotective Agents; Social Behavior

Neuroinflammatory response triggered by the stimulation of matrix metalloproteinases plays a pivotal role in the development of autistic phenotype. MMPs stimulate inflammatory cytokines release along with mitochondrial deficits that ultimately lead to neuronal dysfunction and precipitate autistic symptoms. The aim of the present study was to explore the neuropsychopharmacotherapeutic efficacy of curcumin in the experimental paradigm of autism spectrum disorders.. 1M propanoic acid (4μl) was infused over 10min into the anterior portion of the caudoputamen to induce autistic behavior in rats. Curcumin (50, 100 and 200mg/kg) was administered per orally starting from 2nd day of surgery and continued up to 28th day. Rats were tested for various neurobehavioural paradigms like social interaction, stereotypy, locomotor activity, anxiety, novelty, depression, spatial learning and memory as well as for repetitive and pervasive behavior. In addition, biochemical tests for oxidative stress, mitochondrial complexes, TNF-α and MMP-9 were also carried out.. Intracerebroventricular injection of propanoic acid produced neurological, sensory, behavioral, biochemical and molecular deficits which were assessed as endophenotype of autism spectrum disorders. Regular treatment with curcumin for four weeks significantly and dose dependently restored neurological, behavioral, biochemical and molecular changes associated with autistic phenotype in rats.. The major finding of the study is that curcumin restored the core and associated symptoms of autistic phenotype by suppressing oxidative-nitrosative stress, mitochondrial dysfunction, TNF-α and MMP-9 in PPA-induced autism in rats. Therefore, curcumin can be developed as a potential neuropsychopharmacotherapeutic adjunct for autism spectrum disorders (ASD).

Topics: Animals; Anxiety; Autism Spectrum Disorder; Behavior, Animal; Caudate Nucleus; Central Nervous System Agents; Curcumin; Injections, Intraventricular; Interpersonal Relations; Male; Maze Learning; Memory; Motor Activity; Oxidative Stress; Propionates; Psychotropic Drugs; Putamen; Rats; Rats, Sprague-Dawley; Stereotyped Behavior