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http://dx.doi.org/10.5483/BMBRep.2022.55.4.126

Reactive microglia and mitochondrial unfolded protein response following ventriculomegaly and behavior defects in kaolin-induced hydrocephalus  

Zhu, Jiebo (Department of Medical Science, Chungnam National University School of Medicine)
Lee, Min Joung (Department of Medical Science, Chungnam National University School of Medicine)
Chang, Hee Jin (Department of Medical Science, Chungnam National University School of Medicine)
Ju, Xianshu (Department of Medical Science, Chungnam National University School of Medicine)
Cui, Jianchen (Department of Medical Science, Chungnam National University School of Medicine)
Lee, Yu Lim (Department of Medical Science, Chungnam National University School of Medicine)
Go, Dahyun (Department of Medical Science, Chungnam National University School of Medicine)
Chung, Woosuk (Department of Medical Science, Chungnam National University School of Medicine)
Oh, Eungseok (Department of Medical Science, Chungnam National University School of Medicine)
Heo, Jun Young (Department of Medical Science, Chungnam National University School of Medicine)
Publication Information
BMB Reports / v.55, no.4, 2022 , pp. 181-186 More about this Journal
Abstract
Ventriculomegaly induced by the abnormal accumulation of cerebrospinal fluid (CSF) leads to hydrocephalus, which is accompanied by neuroinflammation and mitochondrial oxidative stress. The mitochondrial stress activates mitochondrial unfolded protein response (UPRmt), which is essential for mitochondrial protein homeostasis. However, the association of inflammatory response and UPRmt in the pathogenesis of hydrocephalus is still unclear. To assess their relevance in the pathogenesis of hydrocephalus, we established a kaolin-induced hydrocephalus model in 8-week-old male C57BL/6J mice and evaluated it over time. We found that kaolin-injected mice showed prominent ventricular dilation, motor behavior defects at the 3-day, followed by the activation of microglia and UPRmt in the motor cortex at the 5-day. In addition, PARP-1/NF-κB signaling and apoptotic cell death appeared at the 5-day. Taken together, our findings demonstrate that activation of microglia and UPRmt occurs after hydrocephalic ventricular expansion and behavioral abnormalities which could be lead to apoptotic neuronal cell death, providing a new perspective on the pathogenic mechanism of hydrocephalus.
Keywords
Hydrocephalus; Microglia; Neuroinflammation; UPRmt;
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1 Stoica BA, Loane DJ, Zhao Z et al (2014) PARP-1 inhibition attenuates neuronal loss, microglia activation and neurological deficits after traumatic brain injury. J Neurotrauma 31, 758-772   DOI
2 Niu LD, Xu W, Li JQ et al (2019) Genome-wide association study of cerebrospinal fluid neurofilament light levels in non-demented elders. Ann Transl Med 7, 657   DOI
3 Ferris CF, Cai X, Qiao J et al (2019) Life without a brain: Neuroradiological and behavioral evidence of neuroplasticity necessary to sustain brain function in the face of severe hydrocephalus. Sci Rep 9, 16479   DOI
4 Olopade FE, Shokunbi MT and Siren AL (2012) The relationship between ventricular dilatation, neuropathological and neurobehavioural changes in hydrocephalic rats. Fluids Barriers CNS 9, 19   DOI
5 Chen Y, Zhou Z and Min W (2018) Mitochondria, oxidative stress and innate immunity. Front Physiol 9, 1487   DOI
6 Shen Y, Ding M, Xie Z et al (2019) Activation of mitochondrial unfolded protein response in SHSY5Y expressing APP cells and APP/PS1 mice. Front Cell Neurosci 13, 568   DOI
7 Solana E, Poca MA, Sahuquillo J, Benejam B, Junque C and Dronavalli M (2010) Cognitive and motor improvement after retesting in normal-pressure hydrocephalus: a real change or merely a learning effect? J Neurosurg 112, 399-409   DOI
8 Bloch O, Auguste KI, Manley GT and Verkman AS (2006) Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4-deficient mice. J Cereb Blood Flow Metab 26, 1527-1537   DOI
9 Wang Z, Zhang Y, Hu F, Ding J and Wang X (2020) Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus. CNS Neurosci Ther 26, 1230-1240   DOI
10 Kahle KT, Kulkarni AV, Limbrick DD Jr and Warf BC (2016) Hydrocephalus in children. Lancet 387, 788-799   DOI
11 Levine DN (2008) Intracranial pressure and ventricular expansion in hydrocephalus: have we been asking the wrong question? J Neurol Sci 269, 1-11   DOI
12 Chistyakov AV, Hafner H, Sinai A, Kaplan B and Zaaroor M (2012) Motor cortex disinhibition in normal-pressure hydrocephalus. J Neurosurg 116, 453-459   DOI
13 Lenfeldt N, Larsson A, Nyberg L et al (2008) Idiopathic normal pressure hydrocephalus: increased supplementary motor activity accounts for improvement after CSF drainage. Brain 131, 2904-2912   DOI
14 Harris CA, Morales DM, Arshad R, McAllister JP 2nd and Limbrick DD Jr (2021) Cerebrospinal fluid biomarkers of neuroinflammation in children with hydrocephalus and shunt malfunction. Fluids Barriers CNS 18, 4   DOI
15 Goulding DS, Vogel RC, Pandya CD et al (2020) Neonatal hydrocephalus leads to white matter neuroinflammation and injury in the corpus callosum of Ccdc39 hydrocephalic mice. J Neurosurg Pediatr 25, 476-483   DOI
16 Czubowicz K, Glowacki M, Fersten E, Kozlowska E, Strosznajder RP and Czernicki Z (2017) Levels of selected pro- and anti-inflammatory cytokines in cerebrospinal fluid in patients with hydrocephalus. Folia Neuropathol 55, 301-307   DOI
17 Kim ST, Son HJ, Choi JH, Ji IJ and Hwang O (2010) Vertical grid test and modified horizontal grid test are sensitive methods for evaluating motor dysfunctions in the MPTP mouse model of Parkinson's disease. Brain Res 1306, 176-183   DOI
18 Khan OH, Enno TL and Del Bigio MR (2006) Brain damage in neonatal rats following kaolin induction of hydrocephalus. Exp Neurol 200, 311-320   DOI
19 Sorrentino V, Menzies KJ and Auwerx J (2018) Repairing mitochondrial dysfunction in disease. Annu Rev Pharmacol Toxicol 58, 353-389   DOI
20 Collins P (1979) Experimental obstructive hydrocephalus in the rat: a scanning electron microscopic study. Neuropathol Appl Neurobiol 5, 457-468   DOI
21 Sosvorova L, Kanceva R, Vcelak J et al (2015) The comparison of selected cerebrospinal fluid and serum cytokine levels in patients with multiple sclerosis and normal pressure hydrocephalus. Neuro Endocrinol Lett 36, 564-571
22 Xu H, Zhang SL, Tan GW et al (2012) Reactive gliosis and neuroinflammation in rats with communicating hydrocephalus. Neuroscience 218, 317-325   DOI
23 Bras JP, Bravo J, Freitas J et al (2020) TNF-alpha-induced microglia activation requires miR-342: impact on NF-kB signaling and neurotoxicity. Cell Death Dis 11, 415   DOI
24 Gaire BP and Choi JW (2021) Critical roles of lysophospholipid receptors in activation of neuroglia and their neuroinflammatory responses. Int J Mol Sci 22, 7864   DOI
25 Tarkowski E, Tullberg M, Fredman P and Wikkelso C (2003) Normal pressure hydrocephalus triggers intrathecal production of TNF-alpha. Neurobiol Aging 24, 707-714   DOI
26 Spagnuolo C, Moccia S and Russo GL (2018) Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur J Med Chem 153, 105-115   DOI
27 Pan Z, Yang K, Wang H et al (2020) MFAP4 deficiency alleviates renal fibrosis through inhibition of NF-κB and TGF-β/Smad signaling pathways. FASEB J 34, 14250-14263   DOI
28 Shim I, Ha Y, Chung JY, Lee HJ, Yang KH and Chang JW (2003) Association of learning and memory impairments with changes in the septohippocampal cholinergic system in rats with kaolin-induced hydrocephalus. Neurosurgery 53, 416-425; discussion 425   DOI
29 Gisslen T, Ennis K, Bhandari V and Rao R (2015) Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF-κB expression and leads to microglial activation in the cerebral cortex. Pediatr Res 78, 513-519   DOI
30 Harland M, Torres S, Liu J and Wang X (2020) Neuronal mitochondria modulation of LPS-induced neuroinflammation. J Neurosci 40, 1756-1765   DOI
31 Park JC, Han SH and Mook-Jung I (2020) Peripheral inflammatory biomarkers in Alzheimer's disease: a brief review. BMB Rep 53, 10-19   DOI
32 Duru S, Oria M, Arevalo S et al (2019) Comparative study of intracisternal kaolin injection techniques to induce congenital hydrocephalus in fetal lamb. Childs Nerv Syst 35, 843-849   DOI
33 Olopade FE, Shokunbi MT, Azeez IA, Andrioli A, Scambi I and Bentivoglio M (2019) Neuroinflammatory response in chronic hydrocephalus in juvenile rats. Neuroscience 419, 14-22   DOI
34 Wu KY, Tang FL, Lee D et al (2020) Ependymal Vps35 promotes ependymal cell differentiation and survival, suppresses microglial activation, and prevents neonatal hydrocephalus. J Neurosci 40, 3862-3879   DOI
35 Takase H, Chou SH, Hamanaka G et al (2020) Soluble vascular endothelial-cadherin in CSF after subarachnoid hemorrhage. Neurology 94, e1281-e1293   DOI
36 Sosvorova L, Mohapl M, Vcelak J, Hill M, Vitku J and Hampl R (2015) The impact of selected cytokines in the follow-up of normal pressure hydrocephalus. Physiol Res 64, S283-S290
37 Basati S, Desai B, Alaraj A, Charbel F and Linninger A (2012) Cerebrospinal fluid volume measurements in hydrocephalic rats. J Neurosurg Pediatr 10, 347-354   DOI
38 Delavallee L, Mathiah N, Cabon L et al (2020) Mitochondrial AIF loss causes metabolic reprogramming, caspase-independent cell death blockade, embryonic lethality, and perinatal hydrocephalus. Mol Metab 40, 101027   DOI
39 Jimenez AJ, Rodriguez-Perez LM, Dominguez-Pinos MD et al (2014) Increased levels of tumour necrosis factor alpha (TNFα) but not transforming growth factor-beta 1 (TGFβ1) are associated with the severity of congenital hydrocephalus in the hyh mouse. Neuropathol Appl Neurobiol 40, 911-932   DOI
40 Shpilka T and Haynes CM (2018) The mitochondrial UPR: mechanisms, physiological functions and implications in ageing. Nat Rev Mol Cell Biol 19, 109-120   DOI
41 Joshi AU, Minhas PS, Liddelow SA et al (2019) Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration. Nat Neurosci 22, 1635-1648   DOI
42 Hirsch EC and Hunot S (2009) Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol 8, 382-397   DOI
43 Hassa PO and Hottiger MO (2002) The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders. Cell Mol Life Sci 59, 1534-1553   DOI
44 Malhotra U, Zaidi AH, Kosovec JE et al (2013) Prognostic value and targeted inhibition of survivin expression in esophageal adenocarcinoma and cancer-adjacent squamous epithelium. PLoS One 8, e78343   DOI
45 Pharaoh G, Pulliam D, Hill S, Sataranatarajan K and Van Remmen H (2016) Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPR(MT) and increased resistance to oxidative stress in primary cultures of fibroblasts. Redox Biol 8, 430-438   DOI
46 D'Amico D, Sorrentino V and Auwerx J (2017) Cytosolic proteostasis networks of the mitochondrial stress response. Trends Biochem Sci 42, 712-725   DOI
47 Kwak JH and Lee K (2021) Forebrain glutamatergic neuron-specific Ctcf deletion induces reactive microgliosis and astrogliosis with neuronal loss in adult mouse hippocampus. BMB Rep 54, 317-322   DOI
48 Fischer R and Maier O (2015) Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF. Oxid Med Cell Longev 2015, 610813   DOI
49 Lee Y, Park Y, Nam H, Lee JW and Yu SW (2020) Translocator protein (TSPO): the new story of the old protein in neuroinflammation. BMB Rep 53, 20-27   DOI
50 Melber A and Haynes CM (2018) UPR(mt) regulation and output: a stress response mediated by mitochondrial-nuclear communication. Cell Res 28, 281-295   DOI
51 Silverberg GD, Miller MC, Pascale CL et al (2015) Kaolin-induced chronic hydrocephalus accelerates amyloid deposition and vascular disease in transgenic rats expressing high levels of human APP. Fluids Barriers CNS 12, 2   DOI
52 Osmon KJ, Vyas M, Woodley E, Thompson P and Walia JS (2018) Battery of behavioral tests assessing general locomotion, muscular strength, and coordination in mice. J Vis Exp 131, 55491
53 Schob S, Weiss A, Dieckow J et al (2016) Correlations of ventricular enlargement with rheologically active surfactant proteins in cerebrospinal fluid. Front Aging Neurosci 8, 324