Skip to main content

Advertisement

Log in

Resveratrol attenuates arsenic-induced cognitive deficits via modulation of Estrogen-NMDAR-BDNF signalling pathway in female mouse hippocampus

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Background

Chronic inorganic arsenic (iAs) exposure induces deleterious effects on CNS including oxidative stress, cognitive deficits and altered brain neurochemistry. Little is known about the association between iAs and estrogen receptor expression in brain regions.

Aims and objectives

Owing to the neuroprotective and estrogenic activities of resveratrol (RES), we examined the combined effects of arsenic trioxide (As2O3) and RES on neurobehavioural functions, estrogen signalling and associated neurochemical changes in mouse hippocampus.

Materials and methods

As2O3 alone (2 and 4 mg/kg bw) or along with RES (40 mg/kg bw) was administered orally for 45 days to adult female mice. From days 33 to 45, open field, elevated plus maze and Morris water maze tests were conducted to evaluate locomotion, anxiety and learning and memory. On day 46, animals were euthanized and brain tissue and hippocampi obtained therefrom were processed for atomic absorption spectrophotometry and western blotting respectively.

Results

As2O3 alone exposure resulted in enhanced anxiety levels, reduced locomotion and impaired learning and memory. As2O3-induced behavioural deficits were accompanied by downregulation of estrogen receptor (ERα) expression with a concomitant reduction of BDNF and NMDAR 2B levels in the hippocampus. However, the behavioural alterations and expression of these markers were restored in RES-supplemented mice. Moreover, a dose-dependent iAs accumulation was observed in serum and brain tissues of mice receiving As2O3 alone whereas simultaneous administration of As2O3 with RES facilitated iAs efflux.

Conclusions

These results suggest that reduced ERα expression with associated downregulation of BDNF and NMDAR 2B levels could be a mechanism by which iAs induces cognitive impairment; hence, the modulation of estrogen-NMDAR-BDNF pathway by RES represents a potential avenue to recover behavioural deficits induced by this neurotoxin.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

Download references

Acknowledgements

We acknowledge the support extended by Dr. S.B. Ray (Professor, Department of Anatomy, AIIMS, New Delhi) in final review of manuscript.

Funding

This study was financially supported by the Department of Anatomy, All India Institute of Medical Sciences, New Delhi (India).

Author information

Authors and Affiliations

Authors

Contributions

Mehta K and Dhar P designed and conceptualized the study. Mehta K wrote the original draft and edited the manuscript. Mehta K performed the experimental procedures, data collection, analysis. Pandey KK and Kaur B helped in performing the behavioural assessment. Kaler S performed final review and editing of the manuscript. All the authors evaluated the final submission and agreed with its content.

Corresponding author

Correspondence to Saroj Kaler.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Highlights

iAs exposure induces hippocampus-mediated behavioural deficits.

• Differential effects of iAs exposure on ER expression; iAs exposure reduced the ERα expression but did not alter ERβ expression.

iAs exposure reduced the levels of potential biomarkers of cognitive function (Glutamate receptor NMDAR 2B subunit and BDNF).

• RES improved cognitive performance and restored the ERα, NMDAR 2B and BDNF expression levels.

• The proposed mechanisms of neuroprotective effects augmented by RES might include its inherent antioxidative properties and estrogenic actions.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mehta, K., Pandey, K.K., Kaur, B. et al. Resveratrol attenuates arsenic-induced cognitive deficits via modulation of Estrogen-NMDAR-BDNF signalling pathway in female mouse hippocampus. Psychopharmacology 238, 2485–2502 (2021). https://doi.org/10.1007/s00213-021-05871-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-021-05871-2

Keywords

Navigation