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Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy.

ABSTRACT: Interleukin 17A (IL-17A) was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications. However, the role of IL-17A in diabetic encephalopathy remains poorly understood. In this study, we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a^-/- mice with spontaneously diabetic Ins2^Akita (Akita) mice. Blood glucose levels and body weights were monitored from 2-32 weeks of age. When mice were 32 weeks of age, behavioral tests were performed, including a novel object recognition test for assessing short-term memory and learning and a Morris water maze test for evaluating hippocampus-dependent spatial learning and memory. IL-17A levels in the serum, cerebrospinal fluid, and hippocampus were detected with enzyme-linked immunosorbent assays and real-time quantitative polymerase chain reaction. Moreover, proteins related to cognitive dysfunction (amyloid precursor protein, β-amyloid cleavage enzyme 1, p-tau, and tau), apoptosis (caspase-3 and -9), inflammation (inducible nitric oxide synthase and cyclooxygenase 2), and occludin were detected by western blot assays. Pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interferon-γ in serum and hippocampal tissues were measured by enzyme-linked immunosorbent assays. Microglial activation and hippocampal neuronal apoptosis were detected by immunofluorescent staining. Compared with that in wild-type mice, mice with diabetic encephalopathy had higher IL-17A levels in the serum, cerebrospinal fluid, and hippocampus; downregulation of occludin expression; lower cognitive ability; greater loss of hippocampal neurons; increased microglial activation; and higher expression of inflammatory factors in the serum and hippocampus. IL-17A knockout attenuated the abovementioned changes in mice with diabetic encephalopathy. These findings suggest that IL-17A participates in the pathological process of diabetic encephalopathy. Furthermore, IL-17A deficiency reduces diabetic encephalopathy-mediated neuroinflammation and cognitive defects. These results highlight a role for IL-17A as a mediator of diabetic encephalopathy and potential target for the treatment of cognitive impairment induced by diabetic encephalopathy.

SUBMITTER: Fang XX

PROVIDER: S-EPMC9165367 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy.

Fang Xiao-Xia XX Xu Fen-Fen FF Liu Zhan Z Cao Bei-Bei BB Qiu Yi-Hua YH Peng Yu-Ping YP

Neural regeneration research 20221201 12

Interleukin 17A (IL-17A) was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications. However, the role of IL-17A in diabetic encephalopathy remains poorly understood. In this study, we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a<sup>-/-</sup> mice with spontaneously diabetic Ins2<sup>Akita</sup> (Akita) mice. Blood glucose levels and body weights were monitored from 2-32 weeks of age. When mic ...[more]

PMID: 35662228

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Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy.

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Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy.

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