Bacopa monniera (L.) Wettst Ameliorates Behavioral Alterations and Oxidative Markers in Sodium Valproate Induced Autism in Rats

Department of Pharmacology, G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad, 500027 Andhra Pradesh, India.
Neurochemical Research (Impact Factor: 2.59). 02/2012; 37(5):1121-31. DOI: 10.1007/s11064-012-0717-1
Source: PubMed

ABSTRACT Early prenatal or post natal exposure to environmental insults such as valproic acid (VPA), thalidomide and ethanol could induce behavioral alterations similar to autistic symptoms. Bacopa monniera, a renowned plant in ayurvedic medicine is useful in several neurological disorders. The purpose of the present study was to evaluate the effect of B. monniera on VPA induced autism. On 12.5 day of gestation the female pregnant rats were divided into control and VPA treated groups. They were administered saline/VPA (600 mg/kg, i.p.) respectively and allowed to raise their own litters. Group I-male pups of saline treated mothers. On postnatal day (PND) 21 VPA induced autistic male pups were divided into two groups (n = 6); Group II-received saline and Group III-received B. monniera (300 mg/kg/p.o.) from PND 21-35. Behavioral tests (nociception, locomotor activity, exploratory activity, anxiety and social behavior) were performed in both adolescence (PND 30-40) and adulthood (PND 90-110) period. At the end of behavioral testing animals were sacrificed, brain was isolated for biochemical estimations (serotonin, glutathione, catalase and nitric oxide) and histopathological examination. Induction of autism significantly affected normal behavior, increased oxidative stress and serotonin level, altered histoarchitecture of cerebellum (decreased number of purkinje cells, neuronal degeneration and chromatolysis) when compared with normal control group. Treatment with B. monniera significantly (p < 0.05) improved behavioral alterations, decreased oxidative stress markers and restored histoarchitecture of cerebellum. In conclusion, the present study suggests that B. monniera ameliorates the autistic symptoms possibly due to its anti-anxiety, antioxidant and neuro-protective activity.

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    • "Nociceptive changes have also been reported in the past. Single administration of VPA (600 mg/kg) on gestational day (GD) 12.5 shows abnormal pain sensitivity in the adulthood, which is similar to the human autistic patients [5] [14] [15]. Neuroanatomical disorder including a decreased number of neuron in the cranial nerve motor nuclei, cerebellar abnormality [16] and lower number of purkinje cells in the cerebellar vermis [17] in the offspring has been reported after the prenatal VPA administration on GD 12.5. "
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    ABSTRACT: Prenatal exposure to valproic acid on gestational day 12.5 may lead to the impaired behaviour in the offspring, which is similar to the human autistic symptoms. To the contrary, astaxanthin shows neuroprotective effect by its antioxidant mechanism. We aimed to (i) develop mice model of autism and (ii) investigate the effect of astaxanthin on such model animals. Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12.5. Prenatal valproic acid-exposed mice were divided into 2 groups on postnatal day 25 and astaxanthin (2 mg/kg) was given to the experimental group (VPA_AST, n = 10) while saline was given to the control group (VPA, n = 10) for 4 weeks. Behavioural test including social interaction, open field and hot-plate were conducted on postnatal day 25 and oxidative stress markers such as lipid peroxidation, advanced protein oxidation product, nitric oxide, glutathione, and activity of superoxide dismutase and catalase were estimated on postnatal day 26 to confirm mice model of autism and on postnatal day 56 to assess the effect of astaxanthin. On postnatal day 25, prenatal valproic acid-exposed mice exhibited (i) delayed eye opening (ii) longer latency to respond painful stimuli, (iii) poor sociability and social novelty and (iv) high level of anxiety. In addition, an increased level of oxidative stress was found by determining different oxidative stress markers. Treatment with astaxanthin significantly (p < 0.05) improved the behavioural disorder and reduced the oxidative stress in brain and liver. In conclusion, prenatal exposure to valproic day in pregnant mice leads to the development of autism-like features. Astaxanthin improves the impaired behaviour in animal model of autism presumably by its antioxidant activity.
    Behavioural Brain Research 02/2015; 30. DOI:10.1016/j.bbr.2015.02.041 · 3.03 Impact Factor
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    • "We hypothesise that the increased social interactions in our VPA rats reflect an inconsistency between olfactory development and the ability to understand intraspecific communicating signals. In a more rudimentary form this was observed by Schneider and Przewlocki (2005) and also Sandhya et al. (2012) as decreased olfactory discrimination of home bedding odour at the age of 9 days. This delay in olfactory development disappeared in subsequent days. "
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    ABSTRACT: Autism is a neurodevelopmental disorder characterised by the disruption of social interactions. Autistic animal models play a crucial role in neurophysiologic research on this disorder. One of these models is based on rats that have been prenatally treated with valproic acid - VPA rats. The aim of our study performed with this model was to investigate changes in sociability and gene expression of neuropeptides and receptors involved in regulating social behaviour. We focused on gene expression in the hypothalamus, where the neuropeptides oxytocin (OT) and arginine-vasopressin (AVP) are produced, as well as oxytocin receptors (OTR) in certain neuronal structures involved in the creation of social abilities. Our research showed that VPA rats spent more time in the part with an unknown animal and less time in the central part of a three chamber sociability test apparatus than control animals. The latency period of VPA rats before initiating social contact was decreased. In addition, during weaning, VPA female rats spent more time in direct interaction with an unknown rat. We also found that adult VPA rats had an increased expression of OT in the hypothalamic supraoptic and paraventricular nuclei and of OTR in the medial prefrontal cortex, piriform cortex, cortex-amygdala transition zone and the region of the basolateral and basomedial amygdaloid nuclei compared with controls. To sum up, we observed that a single prenatal injection of VPA increased social behaviour and gene expression of OT and OTR in neurological structures connected with the social behaviour of rats. One unanticipated finding was the absence of one of the core symptoms of autism in VPA rats, suggesting a decreased ability to understand intraspecific communication signals. Copyright © 2015. Published by Elsevier Inc.
    Pharmacology Biochemistry and Behavior 02/2015; 131. DOI:10.1016/j.pbb.2015.01.021 · 2.78 Impact Factor
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    ABSTRACT: Effect of standardized Bacopa monniera (BM; family: Scrophulariaceae) extract (100 and 300 mg/kg) against sodium fluoride (NaF; 100 and 200 ppm)-induced behavioural, biochemical, and neuropathological alterations in mice was evaluated. Akinesia, rotarod (motor coordination), forced swim test (depression), open field test (anxiety), transfer latency (memory), cholinesterase (ChE), and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation) were determined in mice treated with NaF for 30 days alone and in combination with BM. NaF induced motor incoordination, depression, and memory impairment, and these were prevented by coadministration of BM in mice. However, NaF did not alter the weight gain, feed/water consumption, and anxiety profile. Suppression of ChE levels and increased oxidative stress were observed in mice treated with NaF. Coadministration of BM significantly improved the memory, ChE levels, and antioxidant enzymes but failed to alter the fluoride levels in NaF-treated mice. Histopathological studies revealed that BM protected the neuropathological alterations induced by NaF.
    Toxicology and Industrial Health 12/2012; 31(1). DOI:10.1177/0748233712468018 · 1.86 Impact Factor
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