{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T12:41:28Z","timestamp":1760618488304,"version":"build-2065373602"},"reference-count":74,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre, Krak\u00f3w, Poland","award":["2015\/19\/B\/NZ9\/03706"],"award-info":[{"award-number":["2015\/19\/B\/NZ9\/03706"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The hypothalamus is a key regulator of fundamental physiological processes and a site of adult neurogenesis. Allopregnanolone (ALLO) is a neurosteroid that mitigates the adverse effects of stress on the central nervous system and also affects neurogenesis. This study examined the effects of acute stress and ALLO administration (separately or in combination) into the third brain ventricle on the expression of neurotrophins and Trk\u03b2 receptor in distinct hypothalamic areas of sexually active female sheep. Expression of genes encoding brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4) and the Trk\u03b2 receptor was analyzed in the medial basal hypothalamus (MBH), arcuate nucleus (ARC), anterior hypothalamus (AHA), paraventricular nucleus (PVN), and preoptic area (POA). Acute stress stimulated the expression of neurotrophins (BDNF, NGF, and NT-3) in the ARC and PVN, while inhibitory effects predominated in the MBH, AHA and POA. ALLO alone mainly suppressed neurotrophins expression, while stimulatory effects were limited to the BDNF\u2013Trk\u03b2 system in the ARC and Trk\u03b2 in the AHA. When combined with stress, ALLO either counteracted stress-induced increases in neurotrophins expression or produced no effect. The results demonstrate that acute stress can differentially modify neurotrophins mRNA expression in hypothalamic regions, activating neurotrophic activity in specific nuclei. The predominant inhibitory effect of ALLO on neurotrophin synthesis, particularly under conditions of acute stress, may help prevent excessive neuronal activation. Conversely, the upregulation of the BDNF-Trk\u03b2 system in the ARC indicates a positive relationship between this neurosteroid and hypothalamic adult neurogenesis.<\/jats:p>","DOI":"10.3390\/ijms262010062","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T12:17:02Z","timestamp":1760617022000},"page":"10062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression of Neurotrophin Genes in the Hypothalamus of Stressed and Allopregnanolone-Infused Sheep"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5676-1373","authenticated-orcid":false,"given":"Patrycja","family":"M\u0142otkowska","sequence":"first","affiliation":[{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St., 05-110 Jablonna, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-5597","authenticated-orcid":false,"given":"Bartosz","family":"Osuch","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St., 05-110 Jablonna, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"El\u017cbieta","family":"Marciniak","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St., 05-110 Jablonna, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4990-1841","authenticated-orcid":false,"given":"Katarzyna","family":"Roszkowicz-Ostrowska","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St., 05-110 Jablonna, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2556-4983","authenticated-orcid":false,"given":"Tomasz","family":"Misztal","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St., 05-110 Jablonna, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"454","DOI":"10.55782\/ane-2010-1816","article-title":"Neurotrophins and their receptors in early development of the mammalian nervous system","volume":"70","author":"Bartkowska","year":"2010","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-del Ca\u00f1o, C., Varela-Andr\u00e9s, N., Cebri\u00e1n-Le\u00f3n, A., and Deogracias, R. (2024). Neurotrophins and Their Receptors: BDNF\u2019s Role in GABAergic Neurodevelopment and Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158312"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fnins.2016.00026","article-title":"Regulation of Neurogenesis by Neurotrophins during Adulthood: Expected and Unexpected Roles","volume":"10","author":"Vilar","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/B978-0-444-64150-2.00004-6","article-title":"Neurogenesis, neuronal migration, and axon guidance","volume":"173","author":"Accogli","year":"2020","journal-title":"Handb. Clin. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1111\/j.1460-9568.2010.07521.x","article-title":"Emerging new sites for adult neurogenesis in the mammalian brain: A comparative study between the hypothalamus and the classical neurogenic zones","volume":"32","author":"Migaud","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/nn.3079","article-title":"Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche","volume":"15","author":"Lee","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.pneurobio.2018.04.001","article-title":"Regulation and function of neurogenesis in the adult mammalian hypothalamus","volume":"170","author":"Yoo","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/B978-0-12-819975-6.00006-6","article-title":"Neurogenesis in the adult hypothalamus: A distinct form of structural plasticity involved in metabolic and circadian regulation, with potential relevance for human pathophysiology","volume":"179","author":"Sharif","year":"2021","journal-title":"Handb. Clin. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1028223","DOI":"10.3389\/fnmol.2022.1028223","article-title":"Function of brain-derived neurotrophic factor in the hypothalamus: Implications for depression pathology","volume":"15","author":"Autry","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1032224","DOI":"10.3389\/fnmol.2022.1032224","article-title":"BDNF receptor TrkB as the mediator of the antidepressant drug action","volume":"15","author":"Casarotto","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5033","DOI":"10.1038\/s41598-023-30787-6","article-title":"The influence of the BDNF Val66Met genotype on emotional recognition memory in post-traumatic stress disorder","volume":"13","author":"Nicholson","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fnint.2013.00055","article-title":"Brain-Derived Neurotrophic Factor (BDNF) protein levels in anxiety disorders: Systematic review and meta-regression analysis","volume":"7","author":"Suliman","year":"2013","journal-title":"Front. Integr. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Correia, A.S., Cardoso, A., and Vale, N. (2023). BDNF Unveiled: Exploring Its Role in Major Depression Disorder Serotonergic Imbalance and Associated Stress Conditions. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15082081"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1080\/00207454.2018.1527328","article-title":"Direct and indirect evidences of BDNF and NGF as key modulators in depression: Role of antidepressants treatment","volume":"129","author":"Mondal","year":"2019","journal-title":"Int. J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.pbb.2009.11.010","article-title":"Nerve growth factor (NGF) has novel antidepressant-like properties in rats","volume":"94","author":"Overstreet","year":"2010","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.npep.2011.06.002","article-title":"Effects of nerve growth factor (NGF), fluoxetine, and amitriptyline on gene expression profiles in rat brain","volume":"45","author":"McGeary","year":"2011","journal-title":"Neuropeptides"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biopsych.2021.05.008","article-title":"Brain-Derived neurotrophic factor signaling in depression and antidepressant action","volume":"90","author":"Monteggia","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1038\/mp.2011.113","article-title":"Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression","volume":"17","author":"Guilloux","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.jagp.2012.10.026","article-title":"Involvement of brain-derived neurotrophic factor in late-life depression","volume":"21","author":"Dwivedi","year":"2013","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e389","DOI":"10.1038\/tp.2014.26","article-title":"Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders","volume":"4","author":"Ray","year":"2014","journal-title":"Transl. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"433","DOI":"10.2147\/NDT.S5700","article-title":"Brain-derived neurotrophic factor: Role in depression and suicide","volume":"5","author":"Dwivedi","year":"2009","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1176\/appi.ajp.2012.12020248","article-title":"Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder","volume":"169","author":"Tripp","year":"2012","journal-title":"Am. J. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1093\/ijnp\/pyy008","article-title":"Association of BDNF Val66Met polymorphism and brain BDNF levels with major depression and suicide","volume":"21","author":"Youssef","year":"2018","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jchemneu.2016.08.007","article-title":"Exposure to mild stress and brain derived neurotrophin factor (BDNF) immunoreactivity in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei: Comparison between aged and adult rats","volume":"78","author":"Ludkiewicz","year":"2016","journal-title":"J. Chem. Neuroanat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1073\/pnas.1114122109","article-title":"BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus","volume":"109","author":"Jeanneteau","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.psyneuen.2007.09.002","article-title":"Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats","volume":"32","author":"Naert","year":"2007","journal-title":"Psychoneuroendocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.neuroscience.2015.01.052","article-title":"The effect of mild stress stimulation on the nerve growth factor (NGF) and tyrosine kinase receptor A (TrkA) immunoreactivity in the paraventricular nucleus (PVN) of the hypothalamus and hippocampus in aged vs. adult rats","volume":"290","author":"Krawczyk","year":"2015","journal-title":"Neuroscience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e12996","DOI":"10.1111\/jne.12996","article-title":"Allopregnanolone: An overview on its synthesis and effects","volume":"34","author":"Diviccaro","year":"2022","journal-title":"J. Neuroendocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100218","DOI":"10.1016\/j.ynstr.2020.100218","article-title":"The role of allopregnanolone in depressive-like behaviors: Focus on neurotrophic proteins","volume":"12","author":"Almeida","year":"2020","journal-title":"Neurobiol. Stress"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.09.005","article-title":"Allopregnanolone: State of the art","volume":"113","author":"Melcangi","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100367","DOI":"10.1016\/j.coemr.2022.100367","article-title":"Neurosteroids and early-life programming: An updated perspective","volume":"25","author":"Sze","year":"2022","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1190418","DOI":"10.3389\/fnins.2023.1190418","article-title":"New insights into hypothalamic neurogenesis disruption after acute and intense stress: Implications for microglia and inflammation","volume":"17","author":"Cifuentes","year":"2023","journal-title":"Front. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100212","DOI":"10.1016\/j.ynstr.2020.100212","article-title":"Allopregnanolone in postpartum depression: Role in pathophysiology and treatment","volume":"12","author":"Kanes","year":"2020","journal-title":"Neurobiol. Stress"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1469-7793.1999.0081r.x","article-title":"Neurotrophin-3 potentiates excitatory GABAergic synaptic transmission in cultured developing hypothalamic neurones of the rat","volume":"518","author":"Gao","year":"1999","journal-title":"J. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s13238-021-00834-x","article-title":"The hypothalamus for whole-body physiology: From metabolism to aging","volume":"13","author":"Liu","year":"2022","journal-title":"Protein Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3389\/fnins.2017.00570","article-title":"Adult Neurogenesis in Sheep: Characterization and Contribution to Reproduction and Behavior","volume":"11","author":"Batailler","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/j.2040-4603.2015.tb00605.x","article-title":"Hypothalamus as an endocrine organ","volume":"5","author":"Clarke","year":"2015","journal-title":"Compr. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1002\/cne.23514","article-title":"DCX-expressing cells in the vicinity of the hypothalamic neurogenic niche: A comparative study between mouse, sheep, and human tissues","volume":"522","author":"Batailler","year":"2014","journal-title":"J. Comp. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.neuro.24.1.677","article-title":"Neurotrophins: Roles in neuronal development and function","volume":"24","author":"Huang","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.yfrne.2004.04.001","article-title":"Physiology of BDNF: Focus on hypothalamic function","volume":"25","author":"Rage","year":"2004","journal-title":"Front. Neuroendocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.3390\/cells13231928","article-title":"Activation of BDNF-TrkB Signaling in Specific Structures of the Sheep Brain by Kynurenic Acid","volume":"13","author":"Marciniak","year":"2024","journal-title":"Cells"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1530\/JOE-19-0376","article-title":"Allopregnanolone reduces neuroendocrine response to acute stressful stimuli in sheep","volume":"244","author":"Misztal","year":"2020","journal-title":"J. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0306-4522(02)00072-6","article-title":"Immobilization stress rapidly modulates BDNF mRNA expression in the hypothalamus of adult male rats","volume":"112","author":"Rage","year":"2002","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/hipo.10109","article-title":"Rapid induction of BDNF expression in the hippocampus during immobilization stress challenge in adult rats","volume":"13","author":"Marmigere","year":"2003","journal-title":"Hippocampus"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.mcn.2004.07.002","article-title":"A single brain-derived neurotrophic factor injection modifies hypothalamo-pituitary-adrenocortical axis activity in adult male rats","volume":"27","author":"Givalois","year":"2004","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.mcn.2010.08.006","article-title":"Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stress","volume":"46","author":"Naert","year":"2011","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Misztal, T., M\u0142otkowska, P., Marciniak, E., Barszcz, M., Osuch, B., Gajewska, A., and Misztal, A. (2025). Effects of Stress and Allopregnanolone on the Expression of Neurotrophins and TrkB Receptor in the Sheep Hippocampus. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136190"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0896-6273(00)81011-9","article-title":"Identification of a signaling pathway involved in calcium regulation of BDNF expression","volume":"20","author":"Shieh","year":"1998","journal-title":"Neuron"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1523\/JNEUROSCI.4540-10.2011","article-title":"Identification of cis-Elements and Transcription Factors Regulating Neuronal Activity-Dependent Transcription of Human BDNF Gene","volume":"31","author":"Pruunsild","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.neuroscience.2018.07.049","article-title":"BDNF and TrkB Mediate the Improvement from Chronic Stress-induced Spatial Memory Deficits and CA3 Dendritic Retraction","volume":"388","author":"Ortiz","year":"2018","journal-title":"Neuroscience"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.neuroscience.2021.07.011","article-title":"Stress Diminishes BDNF-stimulated TrkB Signaling, TrkB-NMDA Receptor Linkage and Neuronal Activity in the Rat Brain","volume":"473","author":"Robinson","year":"2021","journal-title":"Neuroscience"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"784040","DOI":"10.1155\/2012\/784040","article-title":"NGF, brain and behavioral plasticity","volume":"2012","author":"Berry","year":"2012","journal-title":"Neural Plast."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8555","DOI":"10.1073\/pnas.86.21.8555","article-title":"Nerve growth factor mRNA and protein increase in hypothalamus in a mouse model of aggression","volume":"86","author":"Spillantini","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1523\/JNEUROSCI.15-03-01768.1995","article-title":"Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus","volume":"15","author":"Smith","year":"1995","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.3349\/ymj.2012.53.6.1085","article-title":"Chronic stress induces neurotrophin-3 in rat submandibular gland","volume":"53","author":"Saruta","year":"2012","journal-title":"Yonsei Med. J."},{"key":"ref_56","first-page":"396","article-title":"Variant BDNF Val66Met polymorphism affects stress response and vulnerability to anxiety and depression","volume":"17","author":"Yu","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_57","first-page":"1317","article-title":"The role of neurotrophins related to stress in saliva and salivary glands","volume":"25","author":"Saruta","year":"2010","journal-title":"Histol. Histopathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neuroscience.2013.03.053","article-title":"Allopregnanolone and puberty: Modulatory effect on glutamate and GABA release and expression of 3\u03b1-hydroxysteroid oxidoreductase in the hypothalamus of female rats","volume":"243","author":"Giuliani","year":"2013","journal-title":"Neuroscience"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Almeida, F.B., Pinna, G., and Barros, H.M.T. (2021). The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115495"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.pnpbp.2013.09.005","article-title":"Multifunctional aspects of allopregnanolone in stress and related disorders","volume":"48","author":"Bali","year":"2014","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.1073\/pnas.88.10.4553","article-title":"Stress-Induced Elevations of Gamma-Aminobutyric Acid Type A Receptor-Active Steroids in the Rat Brain","volume":"88","author":"Purdy","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.neuropharm.2012.08.012","article-title":"Allopregnanolone regulates neurogenesis and depressive\/anxiety-like behaviour in a social isolation rodent model of chronic stress","volume":"63","author":"Evans","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3349\/ymj.2010.51.5.661","article-title":"Acute stress and chronic stress change brain-derived neurotrophic factor (BDNF) and tyrosine kinase-coupled receptor (TrkB) expression in both young and aged rat hippocampus","volume":"51","author":"Shi","year":"2010","journal-title":"Yonsei Med. J."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Serra, M.P., Poddighe, L., Boi, M., Sanna, F., Piludu, M.A., Sanna, F., Corda, M.G., Giorgi, O., and Quartu, M. (2018). Effect of Acute Stress on the Expression of BDNF, TrkB, and PSA-NCAM in the Hippocampus of the Roman Rats: A Genetic Model of Vulnerability\/Resistance to Stress-Induced Depression. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123745"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Serra, M.P., Sanna, F., Boi, M., Poddighe, L., Secci, L., Trucas, M., Fern\u00e1ndez-Teruel, A., Corda, M.G., Giorgi, O., and Quartu, M. (2022). Acute Stress Induces Different Changes on the Expression of BDNF and TrkB in the Mesocorticolimbic System of Two Lines of Rats Differing in Their Response to Stressors. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314995"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"112670","DOI":"10.1016\/j.bbr.2020.112670","article-title":"Allopregnanolone induces antidepressant-like effects through BDNF-TrkB signaling independent from AMPA receptor activation in a rat learned helplessness model of depression","volume":"390","author":"Shirayama","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_67","unstructured":"Strzetelski, J. (2014). IZ PIB\u2013INRA Feeding Recommendations for Ruminants and Feed Tables, IZ PIB-INRA. (In Polish)."},{"key":"ref_68","first-page":"1","article-title":"Observations on the stereotaxic configuration of the hypothalamus nuclei in the sheep","volume":"124","author":"Welento","year":"1969","journal-title":"Anat. Anz."},{"key":"ref_69","first-page":"217","article-title":"Methods of investigation of the function of the hypothalamus and hypophysis in chronic experiments in sheep","volume":"14","author":"Traczyk","year":"1963","journal-title":"Acta Physiol. Pol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.theriogenology.2020.09.010","article-title":"Effects of allopregnanolone on central reproductive functions in sheep under natural and stressful conditions","volume":"158","author":"Marciniak","year":"2020","journal-title":"Theriogenology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"106102","DOI":"10.1016\/j.anireprosci.2019.06.014","article-title":"Stimulatory effect of dopamine derivative, salsolinol, on pulsatile luteinizing hormone secretion in seasonally anestrous sheep: Focus on dopamine, kisspeptin and gonadotropin-releasing hormone","volume":"208","author":"Misztal","year":"2019","journal-title":"Anim. Reprod. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1023\/B:BILE.0000019559.84305.47","article-title":"Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper-Excel-based tool using pair-wise correlations","volume":"26","author":"Pfaffl","year":"2004","journal-title":"Biotechnol. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"831838","DOI":"10.3389\/fvets.2022.831838","article-title":"The translational benefits of sheep as large animal models of human neurological disorders","volume":"9","author":"Murray","year":"2022","journal-title":"Front. Vet. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10062\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T12:21:14Z","timestamp":1760617274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":74,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010062"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010062","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]}}}