Brain Derived Neurotrophic Factor in Pregnancy: Stress Responses and Fetal Neurodevelopment: BDNF in Pregnancy

Aafia Afridi; Mohammedelfateh Adam; Soobia Pathan; Karam Ali; Naveed Ahsan; Aneela Sarwer; Akram Ali

doi:10.54393/pjhs.v5i12.2703

Authors

Aafia Afridi Department of Obstetrics and Gynaecology, Hamza Surgical Hospital, Peshawar, Pakistan
Mohammedelfateh Adam Department of Obstetrics and Gynaecology, Galway University Hospital, Ireland
Soobia Pathan Department of Pharmacology and Therapeutics, Liaquat Institute of Medical and Health Sciences, Liaquat University of Medical and Health Sciences, Thatta, Pakistan
Karam Ali Department of Pediatric Medicine, Institute of Maternal and Child Health, People's University of Medical and Health Sciences for Women, Nawabshah, Pakistan
Naveed Ahsan Department of Biochemistry, Bhitai Dental and Medical College, Mirpurkhas, Pakistan
Aneela Sarwer Department of Physiology, Altibri Medical College, Karachi, Pakistan
Akram Ali Department of Chemical Pathology, Shaikh Zayed Hospital, Lahore, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v5i12.2703

Keywords:

Brain-Derived Neurotrophic Factor, Maternal Stress Response, Fetal Brain Development, Neurodevelopmental Outcomes, Stress Biomarkers

Abstract

BDNF was a protein that has crucial role in development of brain in fetuses however its levels were affected by maternal stress response that cause complications. Objective: To study the effects of Brain Derived Neurotrophic Factor (BDNF) in stress response during pregnancy on developing fetus in order to bring clinicopathological correlations. Methods: As PRISMA guidelines suggested, an extensive database search was made from PubMed, Science Direct, and Google Scholar for articles that were released between 2016 and 2024. Included studies analyzed differences in BDNF as a function of maternal stress responses expressed by increased levels of maternal stress activity and changes in maternal brain. This review also included fetal neurodevelopmental issues which related to brain development and stress biomarkers. Google Scholar was used for 60% of the articles with various locations. Results: The review also revealed strong relations between high levels of BDNF and mothers’ stress reactions that included tangible changes in cortisol levels and some parts of the brain as the amygdaloid complex. The effect of maternal stress was observed to be regulated through alteration of brain plasticity by BDNF. Additionally, maternal BDNF concentration has been associated with the changes in fetal brain development such as modifications in brain weight and stress related biomarkers in cord blood serum samples. Conclusions: Maternal stress was hence a critical driver of neurodevelopmental outcomes of fetuses and newborns through BDNF. If implemented, this information may help to understand how BDNF regulates the types of stresses that a mother experiences along with fetal brain development.

References

Dunkel Schetter C. Psychological science on pregnancy: stress processes, biopsychosocial models, and emerging research issues. Annual Review of Psychology. 2011 Jan; 62(1): 531-58. doi: 10.1146/annurev.psych.031809.130727.

Bath KG, Schilit A, Lee FS. Stress effects on BDNF expression: effects of age, sex, and form of stress. Neuroscience. 2013 Jun; 239: 149-56. doi: 10.1016/j.neuroscience.2013.01.074.

Braun K and Champagne FA. Paternal influences on offspring development: behavioural and epigenetic pathways. Journal of Neuroendocrinology. 2014 Oct; 26(10): 697-706. doi: 10.1111/jne.12174.

Garcés MF, Sanchez E, Torres‐Sierra AL, Ruíz‐Parra AI, Angel‐Müller E, Alzate JP et al. Brain‐derived neurotrophic factor is expressed in rat and human placenta and its serum levels are similarly regulated throughout pregnancy in both species. Clinical Endocrinology. 2014 Jul; 81(1): 141-51. doi: 10.1111/cen.12391.

Santos ID, Crivellenti LC, Franco LJ, Sartorelli DS. Relationship between the quality of the pregnant woman's diet and birth weight: a prospective cohort study. European Journal of Clinical Nutrition. 2021 Dec; 75(12): 1819-28. doi: 10.1038/s41430-021-00894-6.

Silvente Troncoso C, Hern'ández-Mart'ínez C, Voltas Moreso NÚ, Canals Sans J, Jard'í Piñana C, Basora Gallisà J et al. Impact of physical activity during pregnancy on infant neurodevelopment. Journal of Reproductive and Infant Psychology. 2024 Aug; 42(4): 620-35. doi: 10.1080/02646838.2022.2155626.

Duarte Azevedo M, Sander S, Tenenbaum L. GDNF, a neuron-derived factor upregulated in glial cells during disease. Journal of Clinical Medicine. 2020 Feb; 9(2): 456. doi: 10.3390/jcm9020456.

Miyasaka Y and Yamamoto N. Neuronal activity patterns regulate brain-derived neurotrophic factor expression in cortical cells via neuronal circuits. Frontiers in Neuroscience. 2021 Dec; 15: 699583. doi: 10.3389/fnins.2021.699583.

Schwartz A, Many A, Shapira U, Rosenberg Friedman M, Yogev Y, Avnon T et al. Perinatal outcomes of pregnancy in the fifth decade and beyond-a comparison of very advanced maternal age groups. Scientific Reports. 2020 Feb; 10(1): 1809. doi: 10.1038/s41598-020-58583-6.

Dai Y, Ding J, Wang Z, Zhang B, Guo Q, Guo J et al. Sex-specific associations of per-and polyfluoroalkyl substances with Brain-Derived Neurotrophic Factors (BDNF) in cord serum. Environmental Research. 2024 Dec; 262: 119922. doi: 10.1016/j.envres.2024.119922.

Lamadé EK, Pedraz-Petrozzi B, Lindner O, Meininger P, Coenen M, Witt SH et al. Stress during pregnancy and fetal serum BDNF in cord blood at birth. Psychoneuroendocrinology. 2024 Jul; 165: 107035. doi: 10.1016/j.psyneuen.2024.107035.

Wang C, Jia X, Jin H, Meng Y, Ye W, Zhang N et al. Maternal exposure to fine particulate matter and brain-derived neurotrophic factor (BDNF) in the fetus: a prospective cohort study. Ecotoxicology and Environmental Safety. 2023 Jun; 257: 114912. doi: 10.1016/j.ecoenv.2023.114912.

Su CH, Liu TY, Chen IT, Ou-Yang MC, Huang LT, Tsai CC et al. Correlations between serum BDNF levels and neurodevelopmental outcomes in infants of mothers with gestational diabetes. Pediatrics & Neonatology. 2021 May; 62(3): 298-304. doi: 10.1016/j.pedneo.2020.12.012.

Mercado L, Rose S, Escalona-Vargas D, Dajani N, Siegel ER, Preissl H et al. Correlating maternal and cord-blood inflammatory markers and BDNF with human fetal brain activity recorded by magnetoencephalography: an exploratory study. Brain, Behavior, & Immunity-Health. 2024 Jun: 100804. doi: 10.1016/j.bbih.2024.100804.

Richter AE, Bekkering-Bauer I, Verkaik-Schakel RN, Leeuwerke M, Tanis JC, Bilardo CM et al. Altered neurodevelopmental DNA methylation status after fetal growth restriction with brain-sparing. Journal of Developmental Origins of Health and Disease. 2022 Jun; 13(3): 378-89. doi: 10.1017/S2040174421000374.

Sivasangari K, Sivamaruthi BS, Chaiyasut C, Rajan KE. Maternal stress-induced changes in adolescent and adult offspring: Neurobehavioural improvement and telomere maintenance. Heliyon. 2023 Oct; 9(10). doi: 10.1016/j.heliyon.2023.e20385.

Abdollahi H, Edalatmanesh MA, Hosseini E, Foroozanfar M. The effects of hesperidin on BDNF/TrkB signaling pathway and oxidative stress parameters in the cerebral cortex of the utero-placental insufficiency fetal rat model. Basic and Clinical Neuroscience. 2021 Jul; 12(4): 511. doi: 10.32598/bcn.2021.2187.1.

Szymanski J and Minichiello L. NKCC1 deficiency in forming hippocampal circuits triggers neurodevelopmental disorder: role of BDNF-TrkB signalling. Brain Sciences. 2022 Apr; 12(4): 502. doi: 10.3390/brainsci12040502.

Yu G, Luo F, Nian M, Li S, Liu B, Feng L et al. Exposure to Perfluoroalkyl substances during pregnancy and fetal BDNF level: a prospective cohort study. Frontiers in Endocrinology. 2021 Jun; 12: 653095. doi: 10.3389/fendo.2021.653095.

Marchese MJ, Li S, Liu B, Zhang JJ, Feng L. Perfluoroalkyl substance exposure and the BDNF pathway in the placental trophoblast. Frontiers in Endocrinology. 2021 Jul; 12: 694885. doi: 10.3389/fendo.2021.694885.

de Mendonça Filho EJ, Barth B, Bandeira DR, de Lima RM, Arcego DM, Dalmaz C et al. Cognitive development and brain gray matter susceptibility to prenatal adversities: Moderation by the prefrontal cortex brain-derived neurotrophic factor gene co-expression network. Frontiers in Neuroscience. 2021 Nov; 15: 744743. doi: 10.3389/fnins.2021.744743.

Pascual-Mancho J, Pintado-Recarte P, Morales-Camino JC, Romero-Román C, Hernández-Martin C, Bravo C et al. Brain-derived neurotrophic factor levels in cord blood from growth restricted fetuses with Doppler alteration compared to adequate for gestational age fetuses. Medicina. 2022 Jan; 58(2): 178. doi: 10.3390/medicina58020178.

Zhang T, Wang H, Ouyang F, Yang H, Zhang J, Zhang N. Does brain-derived neurotrophic factor play a role in the association between maternal prenatal mental health and neurodevelopment in 2-year-old children? Journal of Affective Disorders. 2024 Aug; 359: 171-9. doi: 10.1016/j.jad.2024.05.074.

Granitzer S, Widhalm R, Atteneder S, Fernandez MF, Mustieles V, Zeisler H et al. BDNF and KISS-1 levels in maternal serum, umbilical cord, and placenta: The potential role of maternal levels as effect biomarker. Exposure and Health. 2024 Apr; 16(2): 445-61. doi: 10.1007/s12403-023-00565-w.

Dingsdale H, Nan X, Garay SM, Mueller A, Sumption LA, Chacón-Fernández P et al. The placenta protects the fetal circulation from anxiety-driven elevations in maternal serum levels of brain-derived neurotrophic factor. Translational Psychiatry. 2021 Jan; 11(1): 62. doi: 10.1038/s41398-020-01176-8.

Shchelchkova NA, Kokaya AA, Bezhenar VF, Rozhdestvenskaya OV, Mamedova MA, Mishchenko TA et al. The role of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in chronic fetal oxygen deprivation. Современные технологии в медицине. 2020; 12(1 (eng)): 25-31. doi: 10.17691/stm2020.12.1.03.

Manzari N, Matvienko-Sikar K, Baldoni F, O'Keeffe GW, Khashan AS. Prenatal maternal stress and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis. Social Psychiatry and Psychiatric Epidemiology. 2019 Nov; 54: 1299-309. doi: 10.1007/s00127-019-01745-3.

Jadhav A, Khaire A, Gundu S, Wadhwani N, Chandhiok N, Gupte S et al. Placental neurotrophin levels in gestational diabetes mellitus. International Journal of Developmental Neuroscience. 2021 Jun; 81(4): 352-63. doi: 10.1002/jdn.10107.

Fitzgerald E, Hor K, Drake AJ. Maternal influences on fetal brain development: The role of nutrition, infection and stress, and the potential for intergenerational consequences. Early Human Development. 2020 Nov; 150: 105190. doi: 10.1016/j.earlhumdev.2020.105190.

Sahay A, Kale A, Joshi S. Role of neurotrophins in pregnancy and offspring brain development. Neuropeptides. 2020 Oct; 83: 102075. doi: 10.1016/j.npep.2020.102075.

Li Y, Li F, Qin D, Chen H, Wang J, Wang J et al. The role of brain derived neurotrophic factor in central nervous system. Frontiers in Aging Neuroscience. 2022 Sep; 14: 986443. doi: 10.3389/fnagi.2022.986443.

Xue Z, Shui M, Lin X, Sun Y, Liu J, Wei C et al. Role of BDNF/ProBDNF imbalance in postoperative cognitive dysfunction by modulating synaptic plasticity in aged mice. Frontiers in Aging Neuroscience. 2022 Mar; 14: 780972. doi: 10.3389/fnagi.2022.780972.

Wang CS, Kavalali ET, Monteggia LM. BDNF signaling in context: From synaptic regulation to psychiatric disorders. Cell. 2022 Jan; 185(1): 62-76. doi: 10.1016/j.cell.2021.12.003.

Greenberg PE, Fournier AA, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). The Journal of Clinical Psychiatry. 2015 Feb; 76(2): 5356. doi: 10.4088/JCP.14m09298.

Mosiołek A, Mosiołek J, Jakima S, Pięta A, Szulc A. Effects of antidepressant treatment on neurotrophic factors (BDNF and IGF-1) in patients with Major Depressive Disorder (MDD). Journal of clinical medicine. 2021 Jul; 10(15): 3377. doi: 10.3390/jcm10153377.

Castrén E and Monteggia LM. Brain-derived neurotrophic factor signaling in depression and antidepressant action. Biological Psychiatry. 2021 Jul; 90(2): 128-36. doi: 10.1016/j.biopsych.2021.05.008.

Bélanger JC, Bouchard V, Le Blanc J, Starnino L, Welman M, Chabot-Blanchet M et al. Brain-derived neurotrophic factor mitigates the association between platelet dysfunction and cognitive impairment. Frontiers in Cardiovascular Medicine. 2021 Sep; 8: 739045. doi: 10.3389/fcvm.2021.739045.

Gustafsson D, Klang A, Thams S, Rostami E. The role of BDNF in experimental and clinical traumatic brain injury. International Journal of Molecular Sciences. 2021 Mar; 22(7): 3582. doi: 10.3390/ijms22073582.

Rana T, Behl T, Sehgal A, Srivastava P, Bungau S. Unfolding the role of BDNF as a biomarker for treatment of depression. Journal of Molecular Neuroscience. 2021 Oct; 71(10): 2008-21. doi: 10.1007/s12031-020-01754-x.

Czéh B and Simon M. Benefits of animal models to understand the pathophysiology of depressive disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2021 Mar; 106: 110049. doi: 10.1016/j.pnpbp.2020.110049.

de Miranda AS, de Barros JL, Teixeira AL. Is neurotrophin-3 (NT-3): a potential therapeutic target for depression and anxiety?. Expert Opinion on Therapeutic Targets. 2020 Dec; 24(12): 1225-38. doi: 10.1080/14728222.2020.1846720.