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Acute Sleep Deprivation-Induced Anxiety and Disruption of Hypothalamic Cell Survival and Plasticity: A Mechanistic Study of Protection by Butanol Extract of Tinospora cordifolia

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Abstract

Since sleep is a key homeostatic phenomenon of the body, therefore understanding the complex etiology of the neurological outcome of sleep deprivation (SD) such as anxiety, depression, cognitive dysfunctions, and their management is of utmost importance. The findings of the current study encompass the neurobehavioral as well as hormonal, and neuroinflammatory changes in serum and hypothalamus region of the brain as an outcome of acute SD and their amelioration by pre-treatment with butanol extract of Tinospora cordifolia. SD group animals showed anxiety-like behavior as evident from Elevated Plus Maze data and higher serum cortisol levels, whereas, pre-treatment with B-TCE showed anxiolytic activity and also reduced cortisol levels which was corroborated by an increase in leptin and insulin levels. Further, SD induced elevation of serum pro-inflammatory cytokines IL-6, TNF-α, IL-1β, and MCP-1 and subsequent activation of astroglial cells in the hypothalamus was suppressed in B-TCE pre-treated animals. The current findings suggest that besides the cortical structures, hypothalamus region’s synaptic plasticity and cell survival are adversely impacted by acute SD. Further active ingredients present in B-TCE may be useful for the management of SD-induced anxiety, systemic inflammation, and neuroinflammation by targeting hypothalamic BDNF-TrkB/PI3K-Akt pathways.

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All data generated or analysed during this study are included in this published article.

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Acknowledgements

PB is thankful to the Department of Science and Technology-Cognitive Science Research Initiative (DST-CSRI) for fellowship during the course of this work. Authors acknowledge infrastructure provided by University Grants Commission (UGC), India under University with Potential for Excellence (UPE) and Department of Biotechnology (DBT), India under DISC facility.

Funding

This work was supported by the Department of Science and Technology- Cognitive Science Research Initiative (DST-CSRI), Government of India (GOI) [Grant No. C/639/(IFD)/2015-2016] to Gurcharan Kaur. The funding agency has no role in study design, analysis, and data interpretation; in the writing of the manuscript; and in the decision to submit the article for publication.

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  1. Medical Biotechnology Laboratory, Department of Biotechnology, Guru Nanak Dev University, Amritsar, Punjab, 143005, India

    Payal Bajaj & Gurcharan Kaur

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PB and GK designed the study. PB carried out the experiments. PB and GK analyzed the data and wrote the manuscript. GK provided the infrastructure to carry out the work. Both the authors have read and approved the final manuscript.

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Correspondence to Gurcharan Kaur.

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All animal experimental protocols were approved by the Institutional Animal Ethical Committee (IAEC) of Guru Nanak Dev University, Amritsar, Punjab, India (Reference no: 226/CPCSEA/2019/10). Protocols were performed according to the guidelines of ‘Animal care and use’ laid down by IAEC.

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Bajaj, P., Kaur, G. Acute Sleep Deprivation-Induced Anxiety and Disruption of Hypothalamic Cell Survival and Plasticity: A Mechanistic Study of Protection by Butanol Extract of Tinospora cordifolia. Neurochem Res 47, 1692–1706 (2022). https://doi.org/10.1007/s11064-022-03562-8

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