Acute exposure to artificial light at night alters hippocampal vascular structure in mice

•Artificial light at night (ALAN) is a pervasive and disruptive aspect of modern life•This study examined the effects acute ALAN exposure on hippocampal vasculature•ALAN altered vascular structure connectivity in mice•Vascular alterations induced by varied based sex The function cardiovascular system are modulated across day circadian rhythms, making this susceptible to rhythm disruption. Recent evidence demonstrated that short-term disruptor, artificial (ALAN), increased inflammation angiogenic transcripts hippocampi mice. Here, we four nights mouse networks. To do this, analyzed 2D 3D images vasculature transcriptomic profiles mice exposed ALAN. reduced density CA1 CA2/3 female dentate gyrus male Network were also impaired These results demonstrate rapid potent cerebrovascular networks, highlighting importance mitigation context health disease. coordinated rhythms.1Thosar S.S. Butler M.P. Shea S.A. Role disease.J. Clin. Invest. 2018; 128: 2157-2167Crossref PubMed Scopus (193) Google Scholar Circadian rhythms endogenously driven cyclical processes with periods about 24 h (hence circa: about, diem: day). regulate optimize timing various behavioral, physiological, cellular response fluctuating energetic resource availability need for rest.2Rana S. Prabhu S.D. Young M.E. Chronobiological influence over function: good, bad, ugly.Circ. Res. 2020; 126: 258-279Crossref (44) Proper alignment integrity vital health.1Thosar Cardiovascular generated both within rhythmic humoral neuronal signaling cues act system.2Rana For example, mice, myocardial oxidative metabolism varies varying systemic demands during sleep/wake activity.3Young Razeghi P. Cedars A.M. Guthrie P.H. Taegtmeyer H. Intrinsic diurnal variations cardiac contractile function.Circ. 2001; 89: 1199-1208Crossref Aortic tight-junction extracellular matrix vary day, including variation genes such as claudin-5, junctional adhesion molecule-1, elastin.4Rudic R.D. McNamara Reilly D. Grosser T. Curtis Price T.S. Panda Hogenesch J.B. FitzGerald G.A. Bioinformatic analysis gene oscillation aorta.Circulation. 2005; 112: 2716-2724Crossref (124) several other processes, tone,5Panza J.A. Epstein S.E. Quyyumi A.A. tone its relation alpha-sympathetic vasoconstrictor activity.N. Engl. J. Med. 1991; 325: 986-990Crossref blood pressure,6Douma L.G. Gumz M.L. clock-mediated regulation pressure.Free Radic. Biol. 119: 108-114Crossref (132) heart rate,7Black N. D’Souza A. Wang Y. Piggins Dobrzynski Morris G. Boyett M.R. electrophysiology, arrhythmogenesis, underlying mechanisms.Heart Rhythm. 2019; 16: 298-307Abstract Full Text PDF (90) angiogenesis.8Jensen L.D. Gyllenhaal C. Block K. angiogenesis.Biomol. Concepts. 2014; 5: 245-256Crossref (19) coordination many these necessary responding recovering from needs day.2Rana Alignment internal external environment health.9Walker W.H. Walton J.C. DeVries A.C. Nelson R.J. disruption mental health.Transl. Psychiatry. 10: 28Crossref (285) This primarily occurs solar light-dark cues. Disruption leads negative physiological behavioral consequences. Of disruptors present our environments, most pervasive.10Bumgarner J.R. Light disrupted alter physiology behavior.Integr. Comp. 2021; : icab017Google affects growing 80% global human population; metric exceeds 99% US Europe.11Falchi F. Cinzano Duriscoe Kyba C.C.M. Elvidge C.D. Baugh Portnov B.A. Rybnikova N.A. Furgoni R. new world atlas sky brightness.Sci. Adv. 2016; 2: e1600377Crossref (741) caused has detrimental system.12Meléndez-Fernández O.H. Clocks, sex, hearts: how time-of-day, health.Biomolecules. 11: 883Crossref (12) Previous consequences ALAN.13Walker Borniger Gaudier-Diaz M.M. Hecmarie Meléndez-Fernández O. Pascoe J.L. Courtney Acute low-level sufficient induce neurological changes depressive-like behavior.Mol. Psychiatr. 25: 1080-1093Crossref (43) Mice just exhibited neuroinflammation, behavior, importantly, transcript hippocampus.13Walker Female few 5 lux VEGF-A expression elevated Vegfr-1 expression, indicating signaling.13Walker factor14Duffy Bouchier-Hayes D.J. Harmey J.H. Vascular endothelial growth factor (VEGF) role non-endothelial cells: autocrine signalling VEGF.in: VEGF Cancer. Kluwer Academic/Plenum Publishers, 2004: 133-144Crossref Scholar; reduction can reduce function.15Olfert I.M. Howlett R.A. Tang Dalton N.D. Gu Peterson K.L. Wagner P.D. Breen E.C. Muscle-specific deficiency greatly reduces exercise endurance mice.J. Physiol. 2009; 587: 1755-1767Crossref (119) Scholar,16Gharakhanian Su Aprahamian factor-a perivascular adipose tissue impairs macrovascular function.Front. 687Crossref (4) Moreover, VEGFR-1 capable potentiating angiogenesis,17Park Amano Ito Kashiwagi Yamazaki Takeda Shibuya M. Kitasato Majima receptor-1 (VEGFR-1) enhances angiogenesis surgical sponge model.Biomed. Pharmacother. 78: 140-149Crossref (13) but sequester inhibit angiogenesis.18Kikuchi Stevens Harada Oltean Murohara Anti-angiogenic isoform renal disease.Adv. Chem. 88: 1-33Crossref Based evidence, hypothesized alters hippocampus CFW We tested hypothesis examining sections lectin-labeled vasculature, large-scale reconstructions corrosion casting, bulk-sequencing transcriptome profiling. assess (4 nights) vascularity, first perfused fluorescently labeled lectin, carbohydrate-binding protein used label vasculature. Following imaging, CA1, CA2/3, (DG) manually segmented examine percent area fraction (PAF) lectin staining (Figures 1A–1H ). There no differences PAF (see Summary Table), so between sexes combined subsequent analyses. Reduced was observed (Figure 1I) DG 1K) ALAN, supporting disrupts structure. Segmented not significantly different 1J). observation density, sought comprehensively region-wide cerebrovasculature casts created using casting procedure imaged μCT.19Quintana D.D. Lewis Anantula Garcia Sarkar S.N. Cavendish J.Z. Brown C.M. Simpkins J.W. cerebral angiome: high resolution microct imaging whole brain mice.Neuroimage. 202: 116109Crossref (17) enabled segmentation quantification numerous characteristics. networks be characterized whole-network topology mean features individual segments.20Kirst Skriabine Vieites-Prado Topilko Bertin Gerschenfeld Verny Michalski Tessier-Lavigne Renier Mapping fine-scale organization plasticity vasculature.Cell. 180: 780-795.e25Abstract (117) First, vascularization radii vessels per mm3 all three regions. groups separated analyses because regions (e.g., Figures 3A–3C, S2). In 2A ; nfemales = 7–8, nmales 5–7) 2B) 4–7 μm reduced. Similarly, 3–6 radius 2F; Video S1). well there an interaction size reductions 2C) or 2F).Figure 3ALAN topological miceShow full caption(A–D) network volume (A) surface (B) examined. assessed branchpoint (C) endpoint (D) (n 7–8 females/group, n 5–7 males/group). Data two-way ANOVA planned multiple comparisons made Fisher’s LSD. # - Main effect lighting condition. represented ± SEM. ∗p < 0.05, ∗∗p 0.01, ∗∗∗p 0.001, ∗∗∗∗p 0.0001.View Large Image Figure ViewerDownload Hi-res image Download (PPT) (A–D) 0.0001. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJjNmUxZDUyYTg5Y2U3YjRjOWZkOTk2NjA0NDY1MTdlMyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjg3ODQ4NzQ1fQ.gTGaPiYIMm0kSFJ4F0vbeTiiZdt2PhLBkQaesAbH6z5qFVHsDOMlA91GZxv_w9yZprwUeyKWHC03KpOxzO5Zn2t43l3pGJzNndXY0dchXuJXdItw6_fcyNHpGYXmJdvo4cjO6qqhBeV8aNqalqLlygybxPF3J8VFHq_ERVJ3TjNLoaPG3O3e7a1bFqRZGIk-MvpsYy_Y6jbaD9MhdlTgwoZn_xO-AFKQj8wfG2cXNDvYLTTfDyvrOY5m4Pp93QoQgJuHtA0LnZ35IyhlxdSAOAMf8ahgFQ-wRiq8fZjTgQvHCseJ9MKB_9v15apjXruXSNqV5AQHETpNkvckcs3H7w .mp4 (12.57 MB) Help files S1. vessel segment related 2 further understand characteristics, μCT datasets. dorsal segmented, described methods. total 3A) 3B) volume. Volume either Next, characteristics segments tortuosity S2F) S2H) No Lastly, topology, metrics connectivity. 3C) 3D) any Finally, gain initial insight into mechanisms which performed bulk-tissue RNA-sequencing dissections Several hundred differentially expressed 4A 4B ), minor overlap 4C). females, ontologies associated maintenance organization, included upregulated Bmp7 downregulated, Col4a4, Col20a1, Lamc2, Lama2, among others 4D 4F). Additional females downregulated Nid1 Ctsg. morphogenesis, angiogenesis, blood-brain barrier maintenance, Fgfr2, Anxa2, Mcam Notch4, Coro1c, Klf4 4G). demonstrates short timescale rapidly Our preliminary perfusion indicates vascularity hippocampus. analysis, following casting. structural revealed small-to-medium sized area, increases tortuosity, indicated decreased density. Follow-up examination patterns morphogenesis organization. presented consistent lines work directly impair function.21Chellappa S.L. Vujovic Williams J.S. Scheer F.A.J.L. Impact disease.Trends Endocrinol. Metabol. 30: 767-779Abstract (108) rats dim levels 1–2 weeks nocturnal systolic pressure, rate responses norepinephrine.22Molcan L. Sutovska Okuliarova Senko Krskova Zeman Dim attenuates suppresses melatonin rats.Life Sci. 231: 116568Crossref (27) same study, aortic nitric oxide synthase.22Molcan Similar spontaneously hypertensive ALAN.23Rumanova V.S. Molcan Consequences low-intensity metabolic parameters rats.Can. Pharmacol. 97: 863-871Crossref (15) pressure variability.23Rumanova Humans 3-day simulated shift paradigm diastolic dipping.24Morris C.J. Purvis T.E. Hu misalignment disease risk factors humans.Proc. Natl. Acad. USA. 113: E1402-E1411Crossref (340) pathology, week rodent model ischemia led mortality, Iba1 immunoreactivity, marker activated microglia/macrophages.25Fonken L.K. Bedrosian T.A. Zhang Weil Z.M. recovery ischemia.Exp. Neurol. 317: 100-109Crossref single infarct penumbral experimental stroke mice.26Weil Fonken Walker Bumgarner Liu Melendez-Fernandez exacerbates outcome.Eur. Neurosci. 52: 4139-4146Crossref (5) Other Per2 proper progenitor cells infarction although cell vitro.27Sun Y.Y. Bai W.W. B. Lu X.T. Xing Y.F. Cheng W. X.Q. Zhao Y.X. Period essential maintain early vitro after Cell Mol. 18: 907-918Crossref (26) research zebra finch hippocampal-specific sex-differential effects. One noted 7 recruitment medial striatum, hippocampus, nidopallium caudale. However, only ALAN.28Moaraf Heiblum Vistoropsky Okuliarová Barnea Artificial neurons finches.Int. 21: 6140Crossref A follow-up finches structures, contrast did increase six exposure.29Moaraf Hefetz Scharf I. Evidence induces structure-specific bird.Biomolecules. 1069Crossref (6) Notably, regions.29Moaraf region- sex-specific tangential complementary study. may have indirectly via inflammation. states neuroinflammation humans species,30Walker Becker-Krail May L.E. biological clocks, calendars, immune function.Semin. Immunopathol. 44: 165-173Crossref (8) remodeling.31Intengan H.D. Schiffrin E.L. remodeling hypertension: roles apoptosis, inflammation, fibrosis.Hypertension. 38: 581-587Crossref Scholar,32Muramatsu Takahashi Miyake Fujimura Mochizuki Yamashita Angiogenesis cns promotes through vessel-derived prostacyclin.Nat. 2012; 1658-1664Crossref (81) Scholar,33Pearson-Leary Eacret Chen Takano Nicholas Bhatnagar Inflammation ventral contributes vulnerability stress.Transl. 2017; 7: e1160Crossref (73) Siberian hamsters exhibit Tnf.34Bedrosian Chronic provokes reversible depression-like phenotype: possible TNF.Mol. 2013; 930-936Crossref (77) Male Tnf Il-635Hogan M.K. Kovalycsik Sun Q. Rajagopalan Combined fine particulate matter C3H/HeNHsd mice.Behav. Brain 2015; 294: 81-88Crossref (39) medullar Il-6.36Bumgarner cold hyperalgesia mechanical allodynia mice.Neuroscience. 434: 111-119Abstract (11) scale previous 3 Il-1β mice.13Walker Elevated determining presence adult thought inflammation.33Pearson-Leary Future seek inflammatory their remodeling. regulated clock genes, implicating ability structure.37Paschos G.K. clocks 2010; 106: 833-841Crossref (137) Indeed, transcription binding sites, E-boxes, D-boxes, F-boxes, ROREs promoter proteins.8Jensen loop development zebrafish.38Jensen Cao Z. Nakamura Yang Bräutigam Andersson Wahlberg E. Länne Hosaka Opposing BMAL1 PERIOD2 VEGF-dependent developing zebrafish.Cell Rep. 231-241Abstract (70) Scholar,39Jensen Clock controls angiogenesis.Cell Cycle. 12: 405-408Crossref (34) An assessment synchronization pericytes tube formation counts relative desynchronized cells, remodeling.40Mastrullo V. Van Der Veen D.R. Gupta Matos R.S. Johnston J.D. McVey Madeddu Velliou E.G. Campagnolo Pericytes’ affect cells’ 3d engineered scaffold.Front. 2022; 785Google Further, Bmal1 knockout pathological carotid artery remodeling.41Anea C.B. Stepp D.W. Simkins G.B. Reed Fulton Rudic dysfunctional clock.Circulation. 1510-1517Crossref (209) previously supported results, regional result rhythms42Walton R