Neuroprotective Potential of Bacopa monnieri and Bacoside A Against Dopamine Receptor Dysfunction in the Cerebral Cortex of Neonatal Hypoglycaemic Rats

Abstract

Neonatal hypoglycaemia initiates a series of events leading to neuronal death, even if glucose and glycogen stores return to normal. Disturbances in the cortical dopaminergic function affect memory and cognition. We recommend Bacopa monnieri extract or Bacoside A to treat neonatal hypoglycaemia. We investigated the alterations in dopaminergic functions by studying the Dopamine D1 and D2 receptor subtypes. Receptor-binding studies revealed a significant decrease (p < 0.001) in dopamine D1 receptor number in the hypoglycaemic condition, suggesting cognitive dysfunction. cAMP content was significantly (p < 0.001) downregulated in hypoglycaemic neonatal rats indicating the reduction in cell signalling of the dopamine D1 receptors. It is attributed to the deficits in spatial learning and memory. Hypoglycaemic neonatal rats treated with Bacopa extract alone and Bacoside A ameliorated the dopaminergic and cAMP imbalance as effectively as the glucose therapy. The upregulated Bax expression in the present study indicates the high cell death in hypoglycaemic neonatal rats. Enzyme assay of SOD confirmed cortical cell death due to free radical accumulation. The gene expression of SOD in the cortex was significantly downregulated (p < 0.001). Bacopa treatment showed a significant reversal in the altered gene expression parameters (p < 0.001) of Bax and SOD. Our results suggest that in the rat experimental model of neonatal hypoglycaemia, Bacopa extract improved alterations in D1, D2 receptor expression, cAMP signalling and cell death resulting from oxidative stress. This is an important area of study given the significant motor and cognitive impairment that may arise from neonatal hypoglycaemia if proper treatment is not implemented.

Oxidative stress and cell death in the cerebral cortex as a long-term consequence of neonatal hypoglycemia

“…Nesfatin-1, expressed also in neurones of various brain areas, including the hypothalamic and brainstem nuclei, is an 82 amino-acid peptide originated from post-translational processing of the N-terminal fragment of nucleobindin 2 (NUCB2) (Finelli et al 2014). Some results suggest that (i) a subpopulation of nesfatinergic neurones belongs to the central network activated by hypoglycemia and that nesfatin-1 participates in the triggering of physiological and hormonal counter-regulations observed in response to hypoglycemia (Bonnet et al 2013); (ii) in the rat experimental model of neonatal hypoglycemia, Bacopa extract improved alterations in D1 and D2 receptor expressions, cAMP signalling, and cell death resulting from oxidative stress (Thomas et al 2013). Disturbances in the cortical dopaminergic function affect memory and cognition.…”

“…Wistar neonatal rats used for the experiments were grouped into two groups as follows: (i) control (C), control rats were injected with saline, subcutaneously for 10 days starting from P7; (ii) hypoglycemic (H), hypoglycemic rats received human regular insulin (Actrapid) at a dosage of 10 IU·(kg body mass) −1 ·day −1 subcutaneously and fasted for 240 min in the presence of foster mother (Thomas et al 2013). The animals were injected once daily for 10 days from postnatal day 7 to postnatal day 17 (i.e., P7 to P17; Table 1).…”

Neuroprotective Effects of Bikaverin on H2O2-Induced Oxidative Stress Mediated Neuronal Damage in SH-SY5Y Cell Line

“…Many plant species in diverse regions of the world have been screened for their neuroprotective activity. Extracts of plants such as Green tea (Cho et al 2008), Tripterygium regelii (Choi et al 2010), Rhus verniciflua (Sapkota et al 2011), Eucommia ulmoides (Kwon et al 2012), Hyptis suaveolens (Ghaffari et al 2014), Bacopa monnieri (Thomas et al 2013), and Cyperus rotundus ) were reported to possess antioxidant properties and neuroprotective effects. However, there are very few reports on the neuroprotective compounds of fungal origin.…”

Effect of a Novel Polyherbal Formulation on Diabetes Induced Memory Deficits in Rats

“…Studies have shown that Bacoside A is the main bioactive component and consists of a mixture of saponins (Bacoside A3, bacopaside II, jujubogenin isomer of bacopasaponin C and bacopasaponin C) [52]. Several experimental studies have demonstrated the neuro-protective properties of Bacopa monnieri such as regulation of cholinergic system, enhancing acetylcholine levels, reducing neuroinflammation, amyloid levels and oxidative stress [52][53][54][55][56][57]. Hippophae rhamnoides, commonly known as sea buckthorn or amlavetas, also has been traditionally used for its medicinal properties [58].…”