Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec;25(4):586-595.
doi: 10.1007/s12017-023-08761-2. Epub 2023 Oct 9.

Genetic Variations and Altered Blood mRNA Level of Circadian Genes and BDNF as Risk Factors of Post-Stroke Cognitive Impairment Among Eastern Indians

Dipanwita Sadhukhan  1   2 , Arindam Biswas  3 , Smriti Mishra  3 , Koustav Chatterjee  4 , Daytee Maji  5 , Parama Mitra  3 , Priyanka Mukherjee  3 , Gargi Podder  6 , Biman Kanti Ray  6 , Atanu Biswas  6 , Tapas Kumar Banerjee  3 , Subhra Prakash Hui  7 , Ishani Deb  8
Affiliations

Genetic Variations and Altered Blood mRNA Level of Circadian Genes and BDNF as Risk Factors of Post-Stroke Cognitive Impairment Among Eastern Indians

Dipanwita Sadhukhan et al. Neuromolecular Med. 2023 Dec.

Abstract

Post-stroke cognitive impairment (PSCI) is a clinical outcome in around 30% of post-stroke survivors. BDNF is a major gene in this regard. It is regulated by circadian rhythm. The circadian genes are correlated with stroke timings at molecular level. However, studies suggesting the role of these on susceptibility to PSCI are limited. We aim here to determine: (a) genetic risk variants in circadian clock genes, BDNF and (b) dysregulation in expression level of CLOCK, BMAL1, and BDNF that may be associated with PSCI. BDNF (rs6265G/A, rs56164415C/T), CLOCK (rs1801260T/C, rs4580704G/C), and CRY2 (rs2292912C/G) genes variants were genotyped among 119 post-stroke survivors and 292 controls from Eastern part of India. In addition, we analyzed their gene expression in Peripheral blood Mononuclear cells (PBMC) from 15 PSCI cases and 12 controls. The mRNA data for BDNF was further validated by its plasma level through ELISA (n = 38). Among the studied variants, only rs4580704/CLOCK showed an overall association with PSCI (P = 0.001) and lower Bengali Mini-Mental State Examination (BMSE) score. Its 'C' allele showed a correlation with attention deficiency. The language and memory impairments showed association with rs6265/BDNF, while the 'CC' genotype of rs2292912/CRY2 negatively influenced language and executive function. A significant decrease in gene expression for CLOCK and BDNF in PBMC (influenced by specific genotypes) of PSCI patients was observed than controls. Unlike Pro-BDNF, plasma-level mBDNF was also lower in them. Our results suggest the genetic variants in CLOCK, CRY2, and BDNF as risk factors for PSCI among eastern Indians. At the same time, a lowering expression of CLOCK and BDNF genes in PSCI patients than controls describes their transcriptional dysregulation as underlying mechanism for post-stroke cognitive decline.

Keywords: BDNF; Circadian-clock; Polymorphism; Post-stroke cognitive impairment; Risk factors.

PubMed Disclaimer

References

    1. Al-Qazzaz, N. K., Ali, S. H., Ahmad, S. A., Islam, S., & Mohamad, K. (2014). Cognitive impairment and memory dysfunction after a stroke diagnosis: A post-stroke memory assessment. Neuropsychiatric Disease and Treatment, 10, 1677–1691. https://doi.org/10.2147/NDT.S67184 - DOI - PubMed - PMC
    1. Balkaya, M., & Cho, S. (2019). Genetics of stroke recovery: BDNF val66met polymorphism in stroke recovery and its interaction with aging. Neurobiology of Disease, 126, 36–46. https://doi.org/10.1016/j.nbd.2018.08.009 - DOI - PubMed
    1. Bao, M. H., Zhu, S. Z., Gao, X. Z., Sun, H. S., & Feng, Z. P. (2018). Meta-analysis on the association between brain-derived neurotrophic factor polymorphism rs6265 and ischemic stroke, poststroke depression. Journal of Stroke and Cerebrovascular Diseases : The Official Journal of National Stroke Association, 27(6), 1599–1608. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.01.010 - DOI - PubMed
    1. Beker, M. C., Caglayan, B., Yalcin, E., Caglayan, A. B., Turkseven, S., Gurel, B., Kelestemur, T., Sertel, E., Sahin, Z., Kutlu, S., Kilic, U., Baykal, A. T., & Kilic, E. (2018). Time-of-day dependent neuronal injury after ischemic stroke: implication of circadian clock transcriptional factor Bmal1 and survival kinase AKT. Molecular Neurobiology, 55(3), 2565–2576. https://doi.org/10.1007/s12035-017-0524-4 - DOI - PubMed
    1. Biswas, A., Sadhukhan, D., Biswas, A., Das, S. K., Banerjee, T. K., Bal, P. S., Pal, S., Ghosh, A., Ray, K., & Ray, J. (2021). Identification of GBA mutations among neurodegenerative disease patients from eastern India. Neuroscience Letters, 751, 135816. https://doi.org/10.1016/j.neulet.2021.135816 - DOI - PubMed

Publication types

Substances

LinkOut - more resources