دورية أكاديمية
Neuroprotective Effects of Intranasal IGF-1 against Neonatal Lipopolysaccharide-Induced Neurobehavioral Deficits and Neuronal Inflammation in the Substantia Nigra and Locus Coeruleus of Juvenile Rats.
| العنوان: | Neuroprotective Effects of Intranasal IGF-1 against Neonatal Lipopolysaccharide-Induced Neurobehavioral Deficits and Neuronal Inflammation in the Substantia Nigra and Locus Coeruleus of Juvenile Rats. |
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| المؤلفون: | Tien LT; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, ROC., Lee YJ, Pang Y, Lu S, Lee JW, Tseng CH, Bhatt AJ, Savich RD, Fan LW |
| المصدر: | Developmental neuroscience [Dev Neurosci] 2017; Vol. 39 (6), pp. 443-459. Date of Electronic Publication: 2017 Aug 05. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Karger Country of Publication: Switzerland NLM ID: 7809375 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1421-9859 (Electronic) Linking ISSN: 03785866 NLM ISO Abbreviation: Dev Neurosci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel, New York, Karger. |
| مواضيع طبية MeSH: | Dopaminergic Neurons/*drug effects , Insulin-Like Growth Factor I/*pharmacology , Locus Coeruleus/*drug effects , Substantia Nigra/*drug effects, Administration, Intranasal ; Aging ; Animals ; Animals, Newborn ; Behavior, Animal/drug effects ; Brain/metabolism ; Brain Injuries/drug therapy ; Brain Injuries/metabolism ; Dopaminergic Neurons/metabolism ; Female ; Lipopolysaccharides/pharmacology ; Locus Coeruleus/metabolism ; Motor Activity/drug effects ; Neuroprotective Agents/pharmacology ; Rats, Sprague-Dawley ; Substantia Nigra/metabolism |
| مستخلص: | Neonatal lipopolysaccharide (LPS) exposure-induced brain inflammation resulted in motor dysfunction and brain dopaminergic neuronal injury, and increased the risks of neurodegenerative disorders in adult rats. Our previous studies showed that intranasal administration of insulin-like growth factor-1 (IGF-1) protects against LPS-induced white matter injury in the developing rat brain. To further examine whether IGF-1 protects against LPS-induced brain neuronal injury and neurobehavioral dysfunction, recombinant human IGF-1 (rhIGF-1) at a dose of 50 µg/pup was administered intranasally 1 h following intracerebral injection of LPS (1 mg/kg) in postnatal day 5 (P5) Sprague-Dawley rat pups. Neurobehavioral tests were carried out from P7 to P21, and brain neuronal injury was examined at P21. Our results showed that LPS exposure resulted in disturbances of motor behaviors in juvenile rats. Moreover, LPS exposure caused injury to central catecholaminergic neurons, as indicated by a reduction of tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra (SN), ventral tegmental area (VTA) and olfactory bulb (OB), and brain noradrenergic neurons, as indicated by a reduction of TH immunoreactivity in the locus coeruleus (LC) of the P21 rat brain. The LPS-induced reduction of TH+ cells was observed at a greater degree in the SN and LC of the P21 rat brain. Intranasal rhIGF-1 treatment attenuated LPS-induced central catecholaminergic neuronal injury and motor behavioral disturbances, including locomotion, beam walking test and gait analysis. Intranasal rhIGF-1 administration also attenuated LPS-induced elevation of IL-1β levels and numbers of activated microglia, and cyclooxygenase-2+ cells, which were double labeled with TH+ cells in the SN, VTA, OB and LC of the P21 rat brain. These results suggest that IGF-1 may provide protection against neonatal LPS exposure-induced central catecholaminergic neuronal injury and motor behavioral disturbances, and that the protective effects are associated with the inhibition of microglia activation and the reduction of neuronal oxidative stress by the suppression of the neuronal cyclooxygenase-2 expression. (© 2017 S. Karger AG, Basel.) |
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| معلومات مُعتمدة: | R01 NS080844 United States NS NINDS NIH HHS |
| فهرسة مساهمة: | Keywords: Cyclooxygenase-2; Insulin-like growth factor-1; Lipopolysaccharide; Locus coeruleus; Microglia; Neuroinflammation; Substantia nigra; Ventral tegmental area |
| المشرفين على المادة: | 0 (Lipopolysaccharides) 0 (Neuroprotective Agents) 67763-96-6 (Insulin-Like Growth Factor I) |
| تواريخ الأحداث: | Date Created: 20170809 Date Completed: 20180928 Latest Revision: 20240315 |
| رمز التحديث: | 20240315 |
| مُعرف محوري في PubMed: | PMC5799046 |
| DOI: | 10.1159/000477898 |
| PMID: | 28787734 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1421-9859 |
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| DOI: | 10.1159/000477898 |