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

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.

Increased sociability and gene expression of oxytocin and its receptor in the brains of rats affected prenatally by valproic acid

“…Studies performed on VPA rats have mostly described a decreased time spent in exploring an unknown animal, a decreased amount of social exploration, an increased latency to social behaviour and a preference for familiar animals over new social partners (Kim et al, 2011;Ali and Elgoly, 2013;Kerr et al, 2013;Bambini-Junior et al, 2011Sandhya et al, 2012;Schneider and Przewlocki, 2005;Dufour-Rainfray et al, 2010;Foley et al, 2012). According to our knowledge, only a recently published Cohen et al (2013) study has recorded more social investigations and play-fighting in VPA rats compared to control animals.…”

“…According to human studies (Gregory et al, 2009) and studies performed with VPA rats (Kim et al, 2011;Kerr et al, 2013;Ali and Elgoly, 2013;Bambini-Junior et al, 2011Sandhya et al, 2012;Schneider and Przewlocki, 2005;Dufour-Rainfray et al, 2010;Foley et al, 2012), we expected decreased sociability and gene expression of OT and AVP in the hypothalamus connected with decreased expression of OTR in selected structures of the social brain. However, this prediction was not confirmed.…”

“…Studies on VPA rats have revealed alterations in various aspects of complex social behaviour. Pubertal and adult VPA rats showed decreased numbers of social interactions (Schneider and Przewlocki, 2005;Sandhya et al, 2012) as well as a decreased frequency of pinning in combination with increased latency to social behaviour in the social interaction test (Schneider and Przewlocki, 2005). In the three chamber sociability test, VPA rats explored unknown animals less frequently (Bambini-Junior et al, 2011;Foley et al, 2012;Kerr et al, 2013) and spent more time in a part without an unknown animal than controls (Kim et al, 2011;Foley et al, 2012;Ali and Elgoly, 2013;Kerr et al, 2013;Bambini-Junior et al, 2014).…”

“…Valproic acid, a common anticonvulsant, has a teratogenic effect when administered during pregnancy. Its application between gravidity days 11.5 and 12.5 affects the development of the central nervous system, leading to various neuroanatomical changes (Rodier et al, 1996(Rodier et al, , 1997Ingram et al, 2000;Markram et al, 2008;Rinaldi et al, 2008;Sui and Chen, 2012) as well as changes in behaviour related to autistic symptoms (Schneider and Przewlocki, 2005;Dufour-Rainfray et al, 2010;Bambini-Junior et al, 2011;Foley et al, 2012;Sandhya et al, 2012). Studies on VPA rats have revealed alterations in various aspects of complex social behaviour.…”

Valproic acid decreases cell proliferation and migration in the cerebellum of zebrafish larvae

“…However, VPA exposure during the prenatal and postnatal periods is also known to have severe negative effects on the brain and behavior at later adult stages. Adult rats that were prenatally exposed to VPA were found to have behavioral impairments such as decreased rearing and hole-poking along with increased locomotor activity in novel environments (Sandhya et al 2012). VPA reduce slow threshold (T type) calcium channel current and voltage-gated Na + channel activity while γ-aminobutyric acid (GABA) synthesis in the substantia nigra is increased (Kelly et al 1990;Löscher 1999;Ziyatdinova et al 2011).…”