Neuropsychopharmacotherapeutic efficacy of curcumin in experimental paradigm of autism spectrum disorders
Graphical abstract
Curcumin treatment ameliorates the various neurobehavioural, biochemical and molecular deficits induced by PPA in the rat model of ASD.
Introduction
Autism spectrum disorders (ASD) is a complex syndrome which is characterized by a heterogeneous group of neuropsychiatric disorders that affects the brain in the developmental stage [70]. US Center for Disease Control & Prevention (CDC) has reported the prevalence of ASD to be 1 in 68 children in 2014 as compared to 1 in 88 in 2010. Autism Society of India has reported the prevalence rate of autism to be 1 in 250. Currently 10 million people are suffering from ASD in India. ASD shows significant skewness with respect to occurrence in boys having a sex ratio of 4:1 [19], [27], [62]. ASD is characterized by core symptoms like loss of social interaction, non-social approach, impairment of communication as well as by associated symptoms like irritable nature, anxiety, aggression, epilepsy and sensory processing disorder [5], [25], [70].
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 [51], [58]. For the past two decades the scientific community is focusing on the exploration of neuropsychopharmacotherapeutic potential of phytochemicals in the plethora of human ailments. Curcumin (diferuloyl methane) is the primary curcuminoid which is present in the Indian spice turmeric (Curcuma longa) and is regarded as “Indian Solid Gold”. Its several pharmacological activities like being anti-inflammatory, antioxidant, anti-carcinogenic and neuroprotective have been highlighted in various studies [2], [15], [30], [34], [46], [61], [64], [71], [74], [81], [56]. With this background, the current study was designed to explore neuropsychopharmacotherapeutic potential of curcumin against PPA-induced autistic behavior in Sprague–Dawley rats.
Section snippets
Animals
Male Sprague–Dawley rats (250–280 g), 3–4 months old, bred in the Central Animal House Facility of the Panjab University, Chandigarh (India) were used. The animals were housed under standard laboratory conditions, maintained on a 12 h light and dark cycle and had free access to food (Ashirwad Industries, Chandigarh, India) and water. The experimental protocols were approved by the Institutional Animal Ethics Committee of the Panjab University, Chandigarh, and conducted according to the Indian
Effect of curcumin on the time spent in non-social and social interaction in reciprocal social interaction test
The time spent in non-social interaction like self grooming and arena exploration was significantly increased after the administration of PPA (450.8 ± 10 s) as compared to the control group (50.0 ± 20 s), sodium acetate control group (98.0 ± 15 s), PBS control group (99.3 ± 30.0 s) and propanol group (95.3 ± 35.0 s) [F7,32 = 46.30 (p < 0.0001)]. There was significant and dose dependent reduction in the non-social interaction time after regular administration of curcumin (50, 100 and 200 mg/kg), as compared to the
Discussion
Propanoic acid (PPA) serves as an important link between dietary metabolic products and genetic predisposition for development of clinical pathology of ASD [4], [66]. PPA induced ASD model has a clinical significance because short chain fatty acids (SCFAs) such as PPA are produced as a result of breakdown of dietary carbohydrates and amino acids [24] by many gut bacteria such as Clostridia and Desulfovibrio. These bacteria have also been proposed as infectious causes of ASDs [18]. MacFabe et
Statement of interest
There is no conflict of interest.
Acknowledgments
Research grants sanctioned by SERB, Department of Science & Technology (grant no SB/FT/LS-284/2012), All India Council of Technical Education (11-25/RIFD/CAYT/POL-II/2013-14) and University Grants Commission (20-29(12)/2012(BSR), New Delhi to Dr. Anurag Kuhad are gratefully acknowledged. Senior Research Fellowship sanctioned by Indian Council of Medical Research (45/13/2014-Nan/BMS), New Delhi to Ms. Ranjana Bhandari is also gratefully acknowledged.
References (81)
- et al.
Curcumin promotes degradation of inducible nitric oxide synthase and suppresses its enzyme activity in RAW 264.7 cells
Int. Immunopharmacol.
(2011) - et al.
Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment
Brain Res.
(1998) - et al.
Protective effect of curcumin, the active principle of turmeric (Curcuma longa) in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes in rat brain
Pharmacol. Biochem. Behav.
(2008) - et al.
Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children
Pediatr. Neurol.
(2007) - et al.
A note on a simple apparatus for detecting neurological deficit in rats and mice
J. Am. Pharm. Assoc.
(1957) - et al.
Pyrosequencing study of fecal microflora of autistic and control children
Anaerobe
(2010) - et al.
GABAergic and nitriergic modulation by curcumin for its antianxiety-like activity in mice
Brain Res.
(2010) - et al.
Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids
Anal. Biochem.
(1982) - et al.
Water T-maze: a useful assay for determination of repetitive behaviours in mice
J. Neurosci. Methods
(2013) - et al.
The amelioration of phagocytic ability in microglial cells by curcumin through the inhibition of EMF-induced pro-inflammatory responses
J. Neuroinflammation
(2014)