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.

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Acknowledgements

This work was supported by research Grants from the DBT, DST, ICMR, Govt. of India, and the KSCSTE, Govt. of Kerala, to Dr. C. S. Paulose.

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The authors declare that they have no conflict of interest.

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Thomas, R.B., Joy, S., Ajayan, M.S. et al. Neuroprotective Potential of Bacopa monnieri and Bacoside A Against Dopamine Receptor Dysfunction in the Cerebral Cortex of Neonatal Hypoglycaemic Rats. Cell Mol Neurobiol 33, 1065–1074 (2013). https://doi.org/10.1007/s10571-013-9973-0

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Keywords

  • Neonatal hypoglycaemia
  • Dopamine
  • Bacopa monnieri
  • Bacoside A
  • Cerebral cortex