{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:57:25Z","timestamp":1791309445699,"version":"4.3.1"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2013,8,5]],"date-time":"2013-08-05T00:00:00Z","timestamp":1375660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exposure to an enriched environment has been shown to have many positive effects on brain structure and function. Numerous studies have proven that enriched environment can reduce the lesion induced by toxic and traumatic injuries. Impoverished environment, on the other hand, can have deleterious effects on the outcome of neuronal injuries. We have previously shown that enriched conditions have protective effects in retinal injury in newborn rats. It is well-known that the efficacy of neuroprotective strategies can depend on age and gender. The aim of the present study, therefore, was to examine the effects of environmental enrichment and social isolation in retinal ischemia. We used bilateral common carotid artery occlusion to induce retinal hypoperfusion in adult Wistar rats of both genders. Groups were housed in standard, enriched or impoverished conditions. Impoverished environment was induced by social isolation. Retinas were processed for histological analysis after two weeks of survival. In the present study, we show that (1) enriched environment has protective effects in adult ischemic retinal lesion, while (2) impoverished environment further increases the degree of ischemic injury, and (3) that these environmental effects are gender-dependent: females are less responsive to the positive effects of environmental enrichment and more vulnerable to retinal ischemia in social isolation. In summary, our present study shows that the effects of both positive and negative environmental stimuli are gender-dependent in ischemic retinal lesions.<\/jats:p>","DOI":"10.3390\/ijms140816111","type":"journal-article","created":{"date-parts":[[2013,8,5]],"date-time":"2013-08-05T12:16:02Z","timestamp":1375704962000},"page":"16111-16123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gender-Dependent Effects of Enriched Environment and  Social Isolation in Ischemic Retinal Lesion in Adult Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"Peter","family":"Kiss","sequence":"first","affiliation":[{"name":"PTE-MTA \"Lendulet\" PACAP Research Team, Department of Anatomy, University of Pecs,  P\u00e9cs 7624, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"Szabadfi","sequence":"additional","affiliation":[{"name":"Department of Experimental Zoology and Neurobiology, University of Pecs, P\u00e9cs 7624, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Horvath","sequence":"additional","affiliation":[{"name":"PTE-MTA \"Lendulet\" PACAP Research Team, Department of Anatomy, University of Pecs,  P\u00e9cs 7624, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tamas","sequence":"additional","affiliation":[{"name":"PTE-MTA \"Lendulet\" PACAP Research Team, Department of Anatomy, University of Pecs,  P\u00e9cs 7624, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozsef","family":"Farkas","sequence":"additional","affiliation":[{"name":"PTE-MTA \"Lendulet\" PACAP Research Team, Department of Anatomy, University of Pecs,  P\u00e9cs 7624, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Department of Experimental Zoology and Neurobiology, University of Pecs, P\u00e9cs 7624, Hungary"},{"name":"Janos Szentagothai Research Center, University of P\u00e9cs, P\u00e9cs 7624, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Reglodi","sequence":"additional","affiliation":[{"name":"PTE-MTA \"Lendulet\" PACAP Research Team, Department of Anatomy, University of Pecs,  P\u00e9cs 7624, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s12640-010-9229-4","article-title":"Protective effect of curcumin and its combination with piperine (bioavailability enhancer) against haloperidol-associated neurotoxicity: cellular and neurochemical evidence","volume":"20","author":"Bishnoi","year":"2011","journal-title":"Neurotox. Res"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s12640-010-9160-8","article-title":"Therapeutic effect of the combined use of growth hormone releasing peptide-6 and epidermal growth factor in an axonopathy model","volume":"19","author":"Cibrian","year":"2011","journal-title":"Neurotox. Res"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/s12640-012-9315-x","article-title":"Targeting neuro-inflammatory cytokines and oxidative stress by minocycline attenuates quinolinic-acid-induced Huntington\u2019s disease-like symptoms in rats","volume":"22","author":"Kalonia","year":"2012","journal-title":"Neurotox. Res"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/35044558","article-title":"Neural consequences of environmental enrichment","volume":"1","author":"Kempermann","year":"2000","journal-title":"Nat. Rev. Neurosci"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.brainres.2009.05.082","article-title":"Early-life experience alters response of developing brain to seizures","volume":"1285","author":"Kazl","year":"2009","journal-title":"Brain Res"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0006-8993(00)03249-2","article-title":"Enriched environment during development is protective against lead-induced neurotoxicity","volume":"896","author":"Schneider","year":"2001","journal-title":"Brain Res"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.neuroscience.2010.04.047","article-title":"An enriched environment mitigates the brain-disruptive effects of prenatal diethylstilbestrol exposure in mice","volume":"169","author":"Soeda","year":"2010","journal-title":"Neuroscience"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1161\/01.STR.27.2.324","article-title":"Functional outcome in rats transferred to an enriched environment 15 days after focal brain ischemia","volume":"27","author":"Johansson","year":"1996","journal-title":"Stroke"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.neulet.2005.05.016","article-title":"Gene expression profiling of the rat hippocampus one month after focal cerebral ischemia followed by enriched environment","volume":"385","author":"Ronnback","year":"2005","journal-title":"Neurosci. Lett"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.neulet.2011.04.015","article-title":"An enriched environment reverses the synaptic plasticity deficit induced by chronic cerebral hypoperfusion","volume":"502","author":"Zhu","year":"2011","journal-title":"Neurosci. Lett"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3389\/fnins.2011.00042","article-title":"The effect of enriched environment on the outcome of traumatic brain injury; a behavioral, proteomics, and histological study","volume":"5","author":"Kovesdi","year":"2011","journal-title":"Front. Neurosci"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/00004647-200201000-00011","article-title":"Neuronal plasticity and dendritic spines: Effect of environmental enrichment on intact and postischemic rat brain","volume":"22","author":"Johansson","year":"2002","journal-title":"J. Cereb. Blood Flow Metabolism"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/nrn1970","article-title":"Enriched environments, experience-dependent plasticity and disorders of the nervous system","volume":"7","author":"Nithianantharajah","year":"2006","journal-title":"Nat. Rev. Neurosci"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.brainres.2012.05.025","article-title":"Effects of a 4 month enriched environment on the hippocampus and the myelinated fibers in the hippocampus of middle-aged rats","volume":"1465","author":"Qiu","year":"2012","journal-title":"Brain Res"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10809","DOI":"10.1523\/JNEUROSCI.1857-09.2009","article-title":"Setting the pace for retinal development: Environmental enrichment acts through insulin-like growth factor 1 and brain-derived neurotrophic factor","volume":"29","author":"Landi","year":"2009","journal-title":"J. Neurosci"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00702-010-0496-2","article-title":"Combination of intracortically administered VEGF and environmental enrichment enhances brain protection in developing rats","volume":"118","author":"Ortuzar","year":"2011","journal-title":"J. Neural Transm"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1096\/fj.06-6083com","article-title":"Retinal functional development is sensitive to environmental enrichment: a role for BDNF","volume":"21","author":"Landi","year":"2007","journal-title":"FASEB J"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e1160","DOI":"10.1371\/journal.pone.0001160","article-title":"Maternal enrichment during pregnancy accelerates retinal development of the fetus","volume":"2","author":"Sale","year":"2007","journal-title":"PLoS One"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.neulet.2010.10.065","article-title":"Comparison between PACAP- and enriched environment-induced retinal protection in MSG-treated newborn rats","volume":"487","author":"Kiss","year":"2011","journal-title":"Neurosci. Lett"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.brainres.2009.01.004","article-title":"Early postnatal enriched environment decreases retinal degeneration induced by monosodium glutamate treatment","volume":"1259","author":"Szabadfi","year":"2009","journal-title":"Brain Res"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/BF03033919","article-title":"Diazoxide is protective in the rat retina against ischemic injury induced by bilateral carotid occlusion and glutamate-induced degeneration","volume":"12","author":"Atlasz","year":"2007","journal-title":"Neurotox. Res"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3390\/ijms11020544","article-title":"Novel neuroprotective strategies in ischemic retinal lesions","volume":"11","author":"Szabadfi","year":"2010","journal-title":"Int. J. Mol. Sci"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.preteyeres.2003.12.001","article-title":"Retinal ischemia: Mechanisms of damage and potential therapeutic strategies","volume":"223","author":"Osborne","year":"2004","journal-title":"Prog. Retin. Eye Res"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e50726","DOI":"10.1371\/journal.pone.0050726","article-title":"Environmental enrichment extends photoreceptor survival and visual function in a mouse model of retinitis pigmentosa","volume":"11","author":"Barone","year":"2012","journal-title":"PLoS One"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.expneurol.2012.11.017","article-title":"Post-ischemic environmental enrichment protects the retina from ischemic damage in adult rats","volume":"240C","author":"Dorfman","year":"2013","journal-title":"Exp. Neurol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1385\/ENDO:29:2:275","article-title":"Effects of age, gender, and gonadectomy on neurochemistry and behavior in animal models of Parkinson\u2019s disease","volume":"29","author":"Tamas","year":"2006","journal-title":"Endocrine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/hipo.20563","article-title":"Social isolation prevents exercise-induced proliferation of hippocampal progenitor cells in female rats","volume":"19","author":"Leasure","year":"2009","journal-title":"Hippocampus"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1620\/tjem.117.153","article-title":"Effects of isolation on mice in relation to age and sex","volume":"117","author":"Takemoto","year":"1975","journal-title":"Tohoku J. Exp. Med"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.neuroscience.2012.06.016","article-title":"The impact of environmental enrichment on sex-specific neurochemical circuitries\u2014Effects on brain-derived neurotrophic factor and the serotonergic system","volume":"220","author":"Chourbaji","year":"2012","journal-title":"Neuroscience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.npep.2006.06.001","article-title":"Effect of PACAP in 6-OHDA-induced injury of the substantia nigra in intact young and ovariectomized female rats","volume":"40","author":"Reglodi","year":"2006","journal-title":"Neuropeptides"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/0031-9384(95)02043-8","article-title":"Effects of housing on male and female rats: Crowding stresses male but calm females","volume":"58","author":"Brown","year":"1995","journal-title":"Physiol. Behav"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.brainres.2009.06.087","article-title":"Myelination of the corpus callosum in male and female rats following complex environment housing during adulthood","volume":"1288","author":"Markham","year":"2009","journal-title":"Brain Res"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bbr.2006.07.007","article-title":"Environmental enrichment effects in social investigation in rats are gender dependent","volume":"174","author":"Prunell","year":"2006","journal-title":"Behav. Brain Res"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.brainresbull.2004.08.006","article-title":"Chronic stress and social housing differentially affect neurogenesis in male and female rats","volume":"64","author":"Westenbroek","year":"2004","journal-title":"Brain Res. Bull"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.yhbeh.2005.01.004","article-title":"Pair-housing of male and female rats during chronic stress exposure results in gender-specific behavioral responses","volume":"47","author":"Westenbroek","year":"2005","journal-title":"Horm. Behav"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3233\/JAD-2011-110236","article-title":"Effect of environmental enrichment on the immunoendocrine aging of male and female triple-transgenic 3\u00d7Tg-AD mice for Alzheimer\u2019s disease","volume":"25","author":"Arranz","year":"2011","journal-title":"J. Alzheimers Dis"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1002\/jnr.22461","article-title":"Environmental enrichment potentiates thalamocortical transmission and plasticity in the adult rat visual cortex","volume":"88","author":"Mainardi","year":"2010","journal-title":"J. Neurosci. Res"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1002\/ar.22526","article-title":"Enriched environment and white matter in aging brain","volume":"295","author":"Yang","year":"2012","journal-title":"Anat. Rec. (Hoboken)"},{"key":"ref_39","first-page":"92","article-title":"Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective","volume":"230","author":"Young","year":"2012","journal-title":"Behav. Brain Res"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e16726","DOI":"10.1371\/journal.pone.0016726","article-title":"Sensorimotor experience influences recovery of forelimb abilities but not tissue loss after focal cortical compression in adult rats","volume":"6","author":"Martinez","year":"2011","journal-title":"PLoS One"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0306-4522(01)00386-4","article-title":"Environmental enrichment enhances recovery of function but exacerbates ischemic cell death","volume":"107","author":"Farrell","year":"2001","journal-title":"Neuroscience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s12031-010-9406-1","article-title":"PACAP improves functional outcome in excitotoxic retinal lesion: an electroretinographic study","volume":"43","author":"Varga","year":"2011","journal-title":"J. Mol. Neurosci"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nn1899","article-title":"Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition","volume":"10","author":"Sale","year":"2007","journal-title":"Nat. Neurosci"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e62235","DOI":"10.1371\/journal.pone.0062235","article-title":"Enriched Environment prevents hypobaric hypoxia induced memory impairment and neurodegeneration: Role of BDNF\/PI3K\/GSK3\u03b2 pathway coupled with CREB activation","volume":"8","author":"Jain","year":"2013","journal-title":"PLoS One"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1177\/1545968313481277","article-title":"Alteration of synaptic activity-regulating genes underlying functional improvement by long-term exposure to an enriched environment in the adult brain","volume":"27","author":"Lee","year":"2013","journal-title":"Neurorehabil. Neural. Repair"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ijdevneu.2010.09.003","article-title":"Socially isolated rats exhibit changes in dopamine homeostasis pertinent to schizophrenia","volume":"29","author":"Fabricius","year":"2011","journal-title":"Int. J. Dev. Neurosci"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.bbr.2012.01.052","article-title":"Sex differences in the effects of social and physical environment on novelty-induced exploratory behavior and cocaine-stimulated locomotor activity in adolescent rats","volume":"230","author":"Zakharova","year":"2012","journal-title":"Behav. Brain Res"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1089\/neu.2010.1439","article-title":"Experience-dependent plasticity and vision restoration in rats after optic nerve crush","volume":"27","author":"Prilloff","year":"2010","journal-title":"J. Neurotrauma"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1161\/01.STR.29.1.159","article-title":"Gender-linked brain injury in experimental stroke","volume":"29","author":"Alkayed","year":"1998","journal-title":"Stroke"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neuroscience.2005.05.041","article-title":"Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury","volume":"135","author":"Chen","year":"2005","journal-title":"Neuroscience"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0166-2236(00)01821-X","article-title":"Brain damage, sex hormones and recovery: A new role for progesterone and estrogens?","volume":"24","author":"Stein","year":"2001","journal-title":"Trends Neurosci"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/S0014-4886(03)00389-3","article-title":"The importance of gender on the beneficial effects of posttraumatic hypothermia","volume":"184","author":"Suzuki","year":"2003","journal-title":"Exp. Neurol"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1479-5876-6-33","article-title":"Pathways to ischemic neuronal cell death: Are sex differences relevant?","volume":"6","author":"Lang","year":"2008","journal-title":"J. Transl. Med"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/sj.jcbfm.9600196","article-title":"Neuroprotective effect of kappa opioid receptor agonist is gender specific and linked to reduced neuronal nitric oxide","volume":"26","author":"Zeynalov","year":"2006","journal-title":"J. Cereb. Blood Flow Metabolism"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bbr.2010.04.039","article-title":"Housing environment and sex affect behavioral recovery from ischemic brain damage","volume":"214","author":"Saucier","year":"2010","journal-title":"Behav. Brain Res"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.brainres.2007.07.020","article-title":"Enriched environment and the effect of age on ischemic brain damage","volume":"1170","author":"Saucier","year":"2007","journal-title":"Brain Res"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0304-3940(02)01103-5","article-title":"Intervention with environmental enrichment after experimental brain trauma enhances cognitive recovery in male but not female rats","volume":"334","author":"Wagner","year":"2002","journal-title":"Neurosci. Lett"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.physbeh.2011.08.036","article-title":"Social isolation in adolescence alters behaviors in the forced swim and sucrose preference tests in female but not in male rats","volume":"105","author":"Hong","year":"2012","journal-title":"Physiol. Behav"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s12640-009-9049-6","article-title":"Protection against chronic hypoperfusion-induced retinal neurodegeneration by PARP inhibition via activation of PI-3-kinase Akt pathway and suppression of JNK and p38 MAP kinases","volume":"16","author":"Mester","year":"2009","journal-title":"Neurotox. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.brainres.2009.11.080","article-title":"Changes in pro-oxidant and antioxidant enzyme levels during cerebral hypoperfusion in rats","volume":"1321","author":"Hugyecz","year":"2010","journal-title":"Brain Res"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.exer.2005.09.019","article-title":"Complex neurodegeneration in retina following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats","volume":"82","author":"Yamamoto","year":"2006","journal-title":"Exp. Eye Res"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/8\/16111\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:48:26Z","timestamp":1760219306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/8\/16111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,5]]},"references-count":61,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2013,8]]}},"alternative-id":["ijms140816111"],"URL":"https:\/\/doi.org\/10.3390\/ijms140816111","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,5]]}}}