Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 1034
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Interleukin-18 (IL-18) is an inflammatory cytokine linked to major depressive disorder (MDD). MDD is closely related to metabolic disorders, such as diabetes mellitus (DM) and obesity. Moreover, DM is associated with cognitive impairment and promotes apoptosis of hippocampal cells by activating pro-apoptotic and inhibiting anti-apoptotic factors. IL-18-deficient (Il18) mice are obese and have DM. Therefore, we hypothesized a close relationship between IL-18 and death of hippocampal cells, affecting neurogenesis related to behavioral changes such as MDD. Il18 male mice were generated on the C57Bl/6 background and Il18 mice were used as controls. Behavioral, histopathological, and molecular responses, as well as responses to intracerebral recombinant IL-18 administration, were examined. Compared with Il18 mice, Il18 mice had impaired learning and memory and exhibited lower motivation. In the Il18 mice, degenerated mitochondria were detected in synaptic terminals in the molecular layer, the polymorphic layer, and in mossy fibers in the dentate gyrus, suggesting mitochondrial abnormalities. Because of the degeneration of mitochondria in the dentate gyrus, in which pro-apoptotic molecules were upregulated and anti-apoptotic factors were decreased, apoptosis inducers were not cleaved, indicating inhibition of apoptosis. In addition, neurogenesis in the dentate gyrus and the maturity of neuronal cells were decreased in the Il18 mice, while intracerebral administration of recombinant IL-18 promoted significant recovery of neurogenesis. Our findings suggested that IL-18 was indispensable for mitochondrial homeostasis, sustaining clearance of degenerative neural cells, and supporting neurogenesis, normal neuronal maturation and hippocampal function.
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http://dx.doi.org/10.1016/j.neuroscience.2019.04.003 | DOI Listing |
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