Ambiguous Contribution of Glucocorticosteroids to Acute Neuroinflammation in the Hippocampus of Rat

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jul 14

PMID 37446324

Authors

Liya V Tretyakova

Alexey A Kvichansky

Ekaterina S Barkovskaya

Anna O Manolova

Alexey P Bolshakov

Natalia V Gulyaeva

Affiliations

Soon will be listed here.

Abstract

Effects of modulation of glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) on acute neuroinflammatory response were studied in the dorsal (DH) and ventral (VH) parts of the hippocampus of male Wistar rats. Local neuroinflammatory response was induced by administration of bacterial lipopolysaccharide (LPS) to the DH. The modulation of GR and MR was performed by dexamethasone (GR activation), mifepristone, and spironolactone (GR and MR inhibition, respectively). Experimental drugs were delivered to the dentate gyrus of the DH bilaterally by stereotaxic injections. Dexamethasone, mifepristone, and spironolactone were administered either alone (basal conditions) or in combination with LPS (neuroinflammatory conditions). Changes in expression levels of neuroinflammation-related genes and morphology of microglia 3 days after intrahippocampal administration of above substances were assessed. Dexamethasone alone induced a weak proinflammatory response in the hippocampal tissue, while neither mifepristone nor spironolactone showed significant effects. During LPS-induced neuroinflammation, GR activation suppressed expression of selected inflammatory genes, though it did not prevent appearance of activated forms of microglia. In contrast to GR activation, GR or MR inhibition had virtually no influence on LPS-induced inflammatory response. The results suggest glucocorticosteroids ambiguously modulate specific aspects of neuroinflammatory response in the hippocampus of rats at molecular and cellular levels.

References

Bolshakov A, Tretyakova L, Kvichansky A, Gulyaeva N . Glucocorticoids: Dr. Jekyll and Mr. Hyde of Hippocampal Neuroinflammation. Biochemistry (Mosc). 2021; 86(2):156-167. DOI: 10.1134/S0006297921020048. View

Tyagi E, Agrawal R, Nath C, Shukla R . Influence of LPS-induced neuroinflammation on acetylcholinesterase activity in rat brain. J Neuroimmunol. 2008; 205(1-2):51-6. DOI: 10.1016/j.jneuroim.2008.08.015. View

Frank M, Miguel Z, Watkins L, Maier S . Prior exposure to glucocorticoids sensitizes the neuroinflammatory and peripheral inflammatory responses to E. coli lipopolysaccharide. Brain Behav Immun. 2009; 24(1):19-30. DOI: 10.1016/j.bbi.2009.07.008. View

Pires J, Foresti M, Silva C, Rego D, Calio M, Mosini A . Lipopolysaccharide-Induced Systemic Inflammation in the Neonatal Period Increases Microglial Density and Oxidative Stress in the Cerebellum of Adult Rats. Front Cell Neurosci. 2020; 14:142. PMC: 7283979. DOI: 10.3389/fncel.2020.00142. View

Perez-Dominguez M, Avila-Munoz E, Dominguez-Rivas E, Zepeda A . The detrimental effects of lipopolysaccharide-induced neuroinflammation on adult hippocampal neurogenesis depend on the duration of the pro-inflammatory response. Neural Regen Res. 2019; 14(5):817-825. PMC: 6375041. DOI: 10.4103/1673-5374.249229. View

Kvichansky A, Tretyakova L, Volobueva M, Manolova A, Stepanichev M, Onufriev M . Neonatal Proinflammatory Stress and Expression of Neuroinflammation-Associated Genes in the Rat Hippocampus. Biochemistry (Mosc). 2021; 86(6):693-703. DOI: 10.1134/S0006297921060079. View

Zhao J, Bi W, Xiao S, Lan X, Cheng X, Zhang J . Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Sci Rep. 2019; 9(1):5790. PMC: 6453933. DOI: 10.1038/s41598-019-42286-8. View

Willner P, Muscat R, Papp M . Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev. 1992; 16(4):525-34. DOI: 10.1016/s0149-7634(05)80194-0. View

DiSabato D, Quan N, Godbout J . Neuroinflammation: the devil is in the details. J Neurochem. 2016; 139 Suppl 2:136-153. PMC: 5025335. DOI: 10.1111/jnc.13607. View

10.

Frank M, Hershman S, Weber M, Watkins L, Maier S . Chronic exposure to exogenous glucocorticoids primes microglia to pro-inflammatory stimuli and induces NLRP3 mRNA in the hippocampus. Psychoneuroendocrinology. 2014; 40:191-200. PMC: 3912460. DOI: 10.1016/j.psyneuen.2013.11.006. View

11.

Estes M, Kimberley McAllister A . Alterations in immune cells and mediators in the brain: it's not always neuroinflammation!. Brain Pathol. 2014; 24(6):623-30. PMC: 4365495. DOI: 10.1111/bpa.12198. View

12.

Meneses G, Gevorkian G, Florentino A, Bautista M, Espinosa A, Acero G . Intranasal delivery of dexamethasone efficiently controls LPS-induced murine neuroinflammation. Clin Exp Immunol. 2017; 190(3):304-314. PMC: 5680073. DOI: 10.1111/cei.13018. View

13.

Gulyaeva N . Stress-Associated Molecular and Cellular Hippocampal Mechanisms Common for Epilepsy and Comorbid Depressive Disorders. Biochemistry (Mosc). 2021; 86(6):641-656. DOI: 10.1134/S0006297921060031. View

14.

Noh H, Jeon J, Seo H . Systemic injection of LPS induces region-specific neuroinflammation and mitochondrial dysfunction in normal mouse brain. Neurochem Int. 2014; 69:35-40. DOI: 10.1016/j.neuint.2014.02.008. View

15.

Savage J, Carrier M, Tremblay M . Morphology of Microglia Across Contexts of Health and Disease. Methods Mol Biol. 2019; 2034:13-26. DOI: 10.1007/978-1-4939-9658-2_2. View

16.

Cain D, Cidlowski J . Immune regulation by glucocorticoids. Nat Rev Immunol. 2017; 17(4):233-247. PMC: 9761406. DOI: 10.1038/nri.2017.1. View

17.

Qin L, Wu X, Block M, Liu Y, Breese G, Hong J . Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007; 55(5):453-62. PMC: 2871685. DOI: 10.1002/glia.20467. View

18.

Gulyaeva N . Biochemical Mechanisms and Translational Relevance of Hippocampal Vulnerability to Distant Focal Brain Injury: The Price of Stress Response. Biochemistry (Mosc). 2019; 84(11):1306-1328. DOI: 10.1134/S0006297919110087. View

19.

Hamesch K, Borkham-Kamphorst E, Strnad P, Weiskirchen R . Lipopolysaccharide-induced inflammatory liver injury in mice. Lab Anim. 2015; 49(1 Suppl):37-46. DOI: 10.1177/0023677215570087. View

20.

Culig L, Surget A, Bourdey M, Khemissi W, Le Guisquet A, Vogel E . Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress. Neuropharmacology. 2017; 126:179-189. DOI: 10.1016/j.neuropharm.2017.09.009. View