{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:08:19Z","timestamp":1791922099212,"version":"4.3.4"},"reference-count":125,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation (DFG)","award":["CRC1436-A07"],"award-info":[{"award-number":["CRC1436-A07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammatory diseases of the skin, including atopic dermatitis and psoriasis, have gained increasing attention with rising incidences in developed countries over the past decades. While bodily properties, such as immunological responses of the skin, have been described in some detail, interactions with the brain via different routes are less well studied. The suggested routes of the skin\u2013brain axis comprise the immune system, HPA axis, and the peripheral and central nervous system, including microglia responses and structural changes. They provide starting points to investigate the molecular mechanisms of neuropsychiatric comorbidities in AD and psoriasis. To this end, mouse models exist for AD and psoriasis that could be tested for relevant behavioral entities. In this review, we provide an overview of the current mouse models and assays. By combining an extensive behavioral characterization and state-of-the-art genetic interventions with the investigation of underlying molecular pathways, insights into the mechanisms of the skin\u2013brain axis in inflammatory cutaneous diseases are examined, which will spark further research in humans and drive the development of novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms23137484","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T05:41:06Z","timestamp":1657086066000},"page":"7484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Probing the Skin\u2013Brain Axis: New Vistas Using Mouse Models"],"prefix":"10.3390","volume":"23","author":[{"given":"Ali\u0107e","family":"Weiglein","sequence":"first","affiliation":[{"name":"Institute of Anatomy, Otto-von-Guericke-University, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4639-9841","authenticated-orcid":false,"given":"Evelyn","family":"Gaffal","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Otto-von-Guericke-University, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8613-2968","authenticated-orcid":false,"given":"Anne","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Otto-von-Guericke-University, Leipziger Str. 44, 39120 Magdeburg, Germany"},{"name":"Center for Behavioral Brain Sciences (CBBS), Universit\u00e4tsplatz 2, 39106 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/exd.14270","article-title":"Mouse models of atopic dermatitis: A critical reappraisal","volume":"30","author":"Gilhar","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lin, T.-K., Zhong, L., and Santiago, J.L. (2017). Association between stress and the HPA axis in the atopic dermatitis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102131"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000370220","article-title":"Atopic dermatitis: Global epidemiology and risk factors","volume":"66","author":"Nutten","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.3389\/fimmu.2020.01907","article-title":"Research progress in atopic march","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"593","DOI":"10.2147\/CLEP.S315888","article-title":"Prevalence and medications of atopic dermatitis in Germany: Claims data analysis","volume":"13","author":"Sauer","year":"2021","journal-title":"Clin. Epidemol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/jid.2012.339","article-title":"Global epidemiology of psoriasis: A systematic review of incidence and prevalence","volume":"133","author":"Parisi","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Capon, F. (2017). The genetic basis of psoriasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122526"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jaad.2016.07.064","article-title":"Psoriasis and comorbid diseases part I. Epidemiology","volume":"76","author":"Takeshita","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e13969","DOI":"10.1111\/dth.13969","article-title":"Management of psychocutaneous disorders: A practical approach for dermatologists","volume":"33","author":"Jafferany","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nri.2015.5","article-title":"The role of inflammation in depression: From evolutionary imperative to modern treatment target","volume":"16","author":"Miller","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Peters, E.M.J., Michenko, A., Kupfer, J., Kummer, W., Wiegand, S., Niemeier, V., Potekaev, N.N., Lvov, A., and Gieler, U. (2014). Mental stress in atopic dermatitis\u2013neuronal plasticity and the cholinergic system are affected in atopic dermatitis and in response to acute experimental mental stress in a randomized controlled pilot study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113552"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1111\/ijd.14032","article-title":"Stress and psoriasis","volume":"57","author":"Rousset","year":"2018","journal-title":"Int. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.jaad.2016.07.017","article-title":"Association of atopic dermatitis with smoking: A systematic review and meta-analysis","volume":"75","author":"Kantor","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jaad.2018.03.017","article-title":"Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systemic review and meta-analysis","volume":"79","author":"Hamann","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/bjd.20661","article-title":"Association between atopic dermatitis and hypertension: A systematic review and meta-analysis","volume":"186","author":"Yousaf","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/B978-0-444-64123-6.00004-7","article-title":"Hypothalamic-pituitary-adrenal axis and stress","volume":"175","author":"Leistner","year":"2020","journal-title":"Handb. Clin. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pnpbp.2015.11.012","article-title":"Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances","volume":"66","author":"Haapakoski","year":"2016","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s40257-017-0279-8","article-title":"Psoriasis, depression, and inflammatory overlap: A review","volume":"18","author":"Patel","year":"2017","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111065","DOI":"10.1016\/j.biopha.2020.111065","article-title":"Dysregulation of the gut-brain-skin axis and key overlapping inflammatory and immune mechanisms of psoriasis and depression","volume":"137","author":"Wang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1097\/01.all.0000244793.03239.40","article-title":"Anxiety in allergy and atopic dermatitis","volume":"6","author":"Hashizume","year":"2006","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_21","first-page":"136","article-title":"Pathogenesis of stress-associated skin disorders: Exploring the brain-skin axis","volume":"35","author":"Pavlovsky","year":"2017","journal-title":"Curr. Probl. Dermatol."},{"key":"ref_22","first-page":"222","article-title":"Histamine and histamine receptors in allergic dermatitis","volume":"241","author":"Ohtsu","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1001\/archderm.137.1.78","article-title":"Stress and the skin","volume":"137","author":"Tausk","year":"2001","journal-title":"Arch. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s11154-016-9369-9","article-title":"Neuroendocrinology of the skin","volume":"17","author":"Theoharides","year":"2016","journal-title":"Rev. Endocr. Metab. Discord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jsbmb.2013.02.006","article-title":"Steroidogenesis in the skin: Implications for local immune functions","volume":"137","author":"Slominski","year":"2013","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s11154-016-9367-y","article-title":"Stress-related skin disorders","volume":"17","author":"Alexopoulos","year":"2016","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.neuron.2018.03.023","article-title":"Peripheral and central mechanisms of itch","volume":"98","author":"Dong","year":"2018","journal-title":"Neuron"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1021942","DOI":"10.1155\/2016\/1021942","article-title":"IL-4 gene polymorphism may contribute to an increased risk of atopic dermatitis in children","volume":"2016","author":"Shang","year":"2016","journal-title":"Dis. Markers"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11882-018-0788-4","article-title":"Severe atopic dermatitis in children","volume":"18","author":"Huang","year":"2018","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_30","first-page":"2398212820979802","article-title":"The role of cytokines in modulating learning and memory and brain plasticity","volume":"18","author":"Bourgognon","year":"2020","journal-title":"Brain Neurosci. Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neubiorev.2018.01.009","article-title":"The vicious cycle of itch and anxiety","volume":"87","author":"Sanders","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"888","DOI":"10.3389\/fimmu.2018.00888","article-title":"Turning the cytokine responses: An update on interleukin (IL)-4 and IL-13 receptor complexes","volume":"9","author":"Juntilla","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2174\/1871528113666140522104422","article-title":"Brain-skin connection: Stress, inflammation and skin aging","volume":"13","author":"Chen","year":"2014","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bbi.2010.10.015","article-title":"Immune modulation of learning, memory, neural plasticity and neurogenesis","volume":"25","author":"Yirmiya","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/npp.2016.146","article-title":"Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond","volume":"42","author":"Michopoulos","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1159\/000104853","article-title":"Stress system-organization, physiology and immunoregulation","volume":"13","author":"Elenkov","year":"2006","journal-title":"Neuroimmunomodulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"206","DOI":"10.20892\/j.issn.2095-3941.2015.0070","article-title":"Relationship of VEGF\/VEGFR with immune and cancer cells: Staggering or forward?","volume":"13","author":"Li","year":"2016","journal-title":"Cancer Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.trsl.2016.10.002","article-title":"Feeding the microbiota-gut-brain axis: Diet, microbiome, and neuropsychiatry","volume":"179","author":"Sandhu","year":"2017","journal-title":"Transl. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"110142","DOI":"10.1016\/j.pnpbp.2020.110142","article-title":"The effects of psychobiotics on the microbiota-gut-brain axis in early-life stress and neuropsychiatric disorders","volume":"105","author":"Tremblay","year":"2021","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2406594","DOI":"10.1155\/2018\/2406594","article-title":"Oxidative stress and the microbiota\u2013gut\u2013brain axis","volume":"2018","author":"Dumitrescu","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_42","first-page":"1495","article-title":"Microbiota-gut-brain axis as a regulator of reward processes","volume":"157","author":"Carbia","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nri3646","article-title":"Mechanisms regulating skin immunity and inflammation","volume":"14","author":"Pasparakis","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Boche\u0144ska, K., Smoli\u0144ska, E., Moskot, M., Jak\u00f3bkiewicz-Banecka, J., and Gabig-Cimi\u0144ska, M. (2017). Models in the research process of psoriasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122514"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.jaci.2018.01.019","article-title":"Epidermal lipid composition, barrier integrity, and eczematous inflammation are associated with skin microbiome configuration","volume":"141","author":"Baurecht","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1038\/sj.jid.5700807","article-title":"Mouse Models of Psoriasis","volume":"127","author":"Gudjonsson","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.jid.2019.02.014","article-title":"Research techniques made simple: Mouse models of atopic dermatitis","volume":"139","author":"Kim","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1111\/exd.14030","article-title":"House dust mite-treated PAR2 over-expressor mouse: A novel model of atopic dermatitis","volume":"28","author":"Smith","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_49","first-page":"2484","article-title":"Repeated elicitation of contact hypersensitivity induces a shift in cutaneous cytokine milieu from a T helper cell type 1 to a T helper cell type 2 profile","volume":"159","author":"Kitagaki","year":"1997","journal-title":"Immunology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1172\/JCI1647","article-title":"Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice","volume":"101","author":"Spergel","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_51","first-page":"47","article-title":"IL-21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice","volume":"119","author":"Jin","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_52","first-page":"170ra16","article-title":"TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation","volume":"30","author":"Kim","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.jaci.2014.09.015","article-title":"Thymic stromal lymphopoietin signaling in CD4(+) T cells is required for TH2 memory","volume":"135","author":"Wang","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"880","DOI":"10.3892\/ijmm.2020.4630","article-title":"IL-18 knockout alleviates atopic dermatitis-like skin lesions induced by MC903 in a mouse model","volume":"46","author":"Chen","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/978-1-4939-6786-5_8","article-title":"A Mouse Model for Atopic Dermatitis Using Topical Application of Vitamin D3 or of Its Analog MC903","volume":"1559","author":"Schmuth","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1016\/j.jid.2018.06.168","article-title":"Eosinophils determine dermal thickening and water loss in an MC903 model of atopic dermatitis","volume":"138","author":"Naidoo","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1111\/all.13801","article-title":"Spontaneous atopic dermatitis in mice with a defective skin barrier is independent of ILC2 and mediated by IL-1\u03b2","volume":"74","author":"Schwartz","year":"2019","journal-title":"Allergy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.jid.2019.07.716","article-title":"Filaggrin expression and processing deficiencies impair corneocyte surface texture and stiffness in mice","volume":"140","author":"Thyssen","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.1038\/s41598-019-39903-x","article-title":"Methodological refinement of Aldara-induced psoriasisiform dermatitis model in mice","volume":"9","author":"Perkecz","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_60","unstructured":"Sundberg, J.P. (1994). Handbook of Mouse Mutations with Skin and Hair Abnormalities, CRC Press."},{"key":"ref_61","first-page":"972","article-title":"A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice","volume":"143","author":"HogenEsch","year":"1993","journal-title":"Am. J. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/15446","article-title":"Scd1 is expressed in sebaceous glands and is disrupted in the asebia mouse","volume":"23","author":"Zheng","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0092-8674(01)00187-8","article-title":"Interleukin 20: Discovery, receptor identification, and role in epidermal function","volume":"104","author":"Blumberg","year":"2001","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.1210\/en.2005-0156","article-title":"Targeted overexpression of leptin to keratinocytes in transgenic mice results in lack of skin phenotype but induction of early leptin resistance","volume":"146","author":"Rico","year":"2005","journal-title":"Endocrinology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/1523-1747.ep12525484","article-title":"Psoriasiform dermatosis in a rhesus monkey","volume":"76","author":"Lowe","year":"1981","journal-title":"J. Investig. Dermatol."},{"key":"ref_66","first-page":"58","article-title":"Evaluation of psoriatic plaques that spontaneously developed in a cynomolgus monkey (Macaca fascicularis)","volume":"146","author":"Zanolli","year":"1989","journal-title":"Acta. Derm. Venereol. Suppl. (Stockh.)"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/1523-1747.ep12343152","article-title":"Mouse mutations as animal models and biomedical tools for dermatological research","volume":"106","author":"Sundberg","year":"1996","journal-title":"J. Investig. Dermatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/j.0022-202X.2003.12602.x","article-title":"K252a, a high-affinity nerve growth factor receptor blocker, improves psoriasis: An in vivo study using the severe combined immunodeficient mouse-human skin model","volume":"122","author":"Raychaudhuri","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/JLB.3MA0320-363RR","article-title":"Stress aggravates and prolongs imiquimod-induced psoriasis-like epidermal hyperplasia and IL-1\u03b2\/IL-23p40 production","volume":"108","author":"Wang","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1093\/abbs\/gmz095","article-title":"FGF-7 facilitates the process of psoriasis by inducing TNF-\u03b1 expression in HaCaT cells","volume":"51","author":"Pu","year":"2019","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15434","DOI":"10.1038\/s41598-019-51681-0","article-title":"Preventative effects of the partial RANKL peptide MHP1-AcN in a mouse model of imiquimod-induced psoriasis","volume":"9","author":"Ju","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0304-3940(01)01885-7","article-title":"SHIRPA, a protocol for behavioral assessment: Validation for longitudinal study of neurological dysfunction in mice","volume":"306","author":"Rogers","year":"2001","journal-title":"Neurosci. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jneumeth.2014.06.013","article-title":"Comparison of automated home-cage monitoring systems: Emphasis on feeding behaviour, activity and spatial learning following pharmacological interventions","volume":"234","author":"Robinson","year":"2014","journal-title":"J. Neurosci. Methods"},{"key":"ref_74","first-page":"e2609","article-title":"Measuring motor coordination in mice","volume":"75","author":"Deacon","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_75","first-page":"2376","article-title":"Assessment of motor balance and coordination in mice using the balance beam","volume":"10","author":"Luong","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/10253890.2018.1438405","article-title":"Exploratory rearing: A context- and stress-sensitive behavior recorded in the open-field test","volume":"21","author":"Sturman","year":"2018","journal-title":"Stress"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-4939-8994-2_4","article-title":"The Elevated Plus Maze Test for Measuring Anxiety-Like Behavior in Rodents","volume":"1916","author":"Kraeuter","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.physbeh.2014.05.006","article-title":"Assessment of mouse anxiety-like behavior in the light\u2013dark box and open-field arena: Role of equipment and procedure","volume":"133","author":"Kulesskaya","year":"2014","journal-title":"Physiol. Behav."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"341","DOI":"10.9758\/cpn.2020.18.3.341","article-title":"A review of behavioral tests to evaluate different types of anxiety and anti-anxiety effects","volume":"18","author":"Himanshu","year":"2020","journal-title":"Clin. Psychopharmacol. Neuroci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1038\/s41596-018-0011-z","article-title":"Sucrose preference test for measurement of stress-induced anhedonia in mice","volume":"13","author":"Liu","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_81","first-page":"e2473","article-title":"Assessment of social interaction behaviors","volume":"48","author":"Lipina","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"106676","DOI":"10.1016\/j.vascn.2020.106676","article-title":"Marble-burying behavior test as a murine model of compulsive-like behavior","volume":"102","author":"Dixit","year":"2020","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1111\/adb.12325","article-title":"Quantification of alcohol drinking patterns in mice","volume":"20","author":"Eisenhardt","year":"2015","journal-title":"Addict. Biol."},{"key":"ref_84","first-page":"1","article-title":"Examining Object Location and Object Recognition Memory in Mice","volume":"69","author":"Wood","year":"2014","journal-title":"Curr. Protoc. Neurosci."},{"key":"ref_85","first-page":"e58593","article-title":"Novel Object Recognition and Object Location Behavioral Testing in Mice on a Budget","volume":"141","author":"Denninger","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Othman, M.Z., Hassan, Z., and Has, A.T.C. (2022). Morris water maze: A versatile and pertinent tool for assessing spatial learning and memory. Exp. Anim., 21-0120.","DOI":"10.1538\/expanim.21-0120"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.nlm.2011.02.010","article-title":"The effects of binge MDMA on acquisition and reversal learning in a radial-arm maze task","volume":"95","author":"Kay","year":"2011","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/s41380-019-0511-4","article-title":"The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans","volume":"26","author":"Leggio","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"22362","DOI":"10.1038\/s41598-020-79290-2","article-title":"Efficient training of mice on the 5-choice serial reaction time task in an automated rodent training system","volume":"10","author":"Birtalan","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1038\/s41467-020-15121-2","article-title":"Encoding of contextual fear memory in hippocampal\u2013amygdala circuit","volume":"11","author":"Kim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/mp.2016.166","article-title":"The birth, death and resurrection of avoidance: A reconceptualization of a troubled paradigm","volume":"22","author":"LeDoux","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jneumeth.2010.03.026","article-title":"A rotarod test for evaluation of motor skill learning","volume":"189","author":"Shiotsuki","year":"2010","journal-title":"J. Neurosci. Methods"},{"key":"ref_93","unstructured":"(2013). American Psychiatric Association, APA Diagnostic and Statistical Manual of Mental Disorders (DSM-5), American Psychiatric Publishing."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jneumeth.2014.02.001","article-title":"Burrowing and nest building behavior as indicators of well-being in mice","volume":"234","author":"Jirkof","year":"2014","journal-title":"J. Neurosci. Methods"},{"key":"ref_95","first-page":"2813","article-title":"Coping with the forced swim stressor: Current state-of-the-art","volume":"364","author":"Molendjiek","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_96","first-page":"1","article-title":"Forced swim stressor: Trends in usage and mechanistic consideration","volume":"55","author":"Molendjiek","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/bs.irn.2016.02.014","article-title":"Genes and alcohol consumption: Study with mutant mice","volume":"126","author":"Mayfield","year":"2016","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e2744","DOI":"10.21769\/BioProtoc.2744","article-title":"Barnes maze procedure for spatial learning and memory in mice","volume":"8","author":"Pitts","year":"2018","journal-title":"Bio. Protoc."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.cortex.2010.12.002","article-title":"Working memory, attention, and executive function in Alzheimer\u2019s disease and frontotemporal dementia","volume":"48","author":"Stopford","year":"2012","journal-title":"Cortex"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.beproc.2014.11.019","article-title":"Animal memory: A review of delayed matching-to-sample data","volume":"117","author":"Lind","year":"2015","journal-title":"Behav. Processes"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nrn4000","article-title":"Finding the engram","volume":"16","author":"Josselyn","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cpmo.22","article-title":"Cre-loxP-mediated recombination: General principles and experimental considerations","volume":"7","author":"McLellan","year":"2017","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/neuros\/nyab147","article-title":"Chemogenetics: Beyond lesions and electrodes","volume":"89","author":"Poth","year":"2021","journal-title":"Neurosurgery"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.neuron.2017.09.047","article-title":"Optogenetic tools for subcellular application in neuroscience","volume":"96","author":"Rost","year":"2017","journal-title":"Neuron"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3389\/fnbeh.2018.00079","article-title":"Immediate early genes, memory and psychiatric disorders: Focus on c-Fos, Egr1 and Arc","volume":"12","author":"Gallo","year":"2018","journal-title":"Front. Behav. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"569517","DOI":"10.3389\/fnins.2020.569517","article-title":"Dissecting neuronal activation on a brain-wide scale with immediate early genes","volume":"14","author":"Franceschini","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_107","first-page":"011402","article-title":"Interpreting in vivo calcium signals from neuronal cell bodies, axons, and dendrites: A review","volume":"7","author":"Ali","year":"2020","journal-title":"Neurophotonics"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"21848","DOI":"10.1073\/pnas.1011756107","article-title":"Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus","volume":"107","author":"Wall","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1007\/s00429-020-02041-6","article-title":"Neuroanatomical tract-tracing techniques that did go viral","volume":"225","author":"Lanciego","year":"2020","journal-title":"Brain Struct. Funct."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.neubiorev.2019.12.013","article-title":"A neuroscientist\u2019s guide to transgenic mice and other genetic tools","volume":"108","author":"Navabpour","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1002\/glia.23581","article-title":"Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges","volume":"67","author":"Dando","year":"2019","journal-title":"Glia"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"583647","DOI":"10.3389\/fimmu.2020.583647","article-title":"Tools and approaches for studying microglia in vivo","volume":"11","author":"Dando","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"eaay6324","DOI":"10.1126\/sciadv.aay6324","article-title":"Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion","volume":"6","author":"Plemel","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.cell.2013.11.030","article-title":"Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor","volume":"155","author":"Parkhurst","year":"2013","journal-title":"Cell"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/nm.4397","article-title":"Microglia emerge as central players in brain disease","volume":"23","author":"Salter","year":"2017","journal-title":"Nature Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6131","DOI":"10.1038\/s41467-020-19914-3","article-title":"Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury","volume":"11","author":"Wu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1111\/pme.12413","article-title":"The Role of the Dorsal Root Ganglion in the Development of Neuropathic Pain","volume":"15","author":"Krames","year":"2014","journal-title":"Pain Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.cell.2018.06.035","article-title":"A suite of transgenic driver and reporter mouse lines with enhanced brain-cell-type targeting and functionality","volume":"174","author":"Daigle","year":"2018","journal-title":"Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nrg.2017.19","article-title":"Comparative transcriptomics in human and mouse","volume":"18","author":"Breschi","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41586-019-1506-7","article-title":"Conserved cell types with divergent features in human versus mouse cortex","volume":"573","author":"Hodge","year":"2019","journal-title":"Nature"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/icb.2010.173","article-title":"Human immunology: A case for the ascent of non-furry immunology","volume":"89","author":"Khanna","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"ref_122","first-page":"170","article-title":"Mouse models of human disease","volume":"2016","author":"Perlman","year":"2016","journal-title":"Evol. Med. Public Health"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neures.2019.12.009","article-title":"Understanding the circuit basis of cognitive functions using mouse models","volume":"152","author":"Nakajima","year":"2020","journal-title":"Neurosci. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/s41467-017-00205-3","article-title":"HIPP neurons in the dentate gyrus mediate the cholinergic modulation of background context memory salience","volume":"8","author":"Raza","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"104974","DOI":"10.1016\/j.nbd.2020.104974","article-title":"Region-specific involvement of interneuron subpopulaitons in trauma-related pathology and resilience","volume":"143","author":"Demiray","year":"2020","journal-title":"Neurobiol. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7484\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:43:12Z","timestamp":1760139792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,5]]},"references-count":125,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137484"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137484","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,5]]}}}