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Lack of influence of pituitary adenylate-cyclase activating peptide and PAC1 deficiency on astroglial signatures of apolipoprotein E-deficient mice under standard or high cholesterol diet
Given the immunoregulatory roles of pituitary adenylate cyclase-activating polypeptide (PACAP) in general, the effects of the polypeptide on astroglia and the recent evidence showing that astroglial response profiles are affected by apolipoprotein E-(ApoE)-deficiency, the aim of the present study wa...
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| Format: | Dissertation |
| Sprache: | Englisch |
| Veröffentlicht: |
Philipps-Universität Marburg
2023
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| Online Zugang: | PDF-Volltext |
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| Zusammenfassung: | Given the immunoregulatory roles of pituitary adenylate cyclase-activating polypeptide (PACAP) in general, the effects of the polypeptide on astroglia and the recent evidence showing that astroglial response profiles are affected by apolipoprotein E-(ApoE)-deficiency, the aim of the present study was to test whether PACAP-deficiency and/or a deficiency in its receptor PAC1 in ApoE-knockout mice determine astroglial response signatures under standard diet or under high cholesterol diet.
After immunohistochemical staining for the astrocyte marker glial fibrillary acidic protein (GFAP), astrocyte numbers and the proportional area of astrocytes were analyzed in the dentate gyrus, corpus callosum and visual cortex of mice with four different genotypes, including wildtype mice (WT), ApoE-single-knockout mice (ApoE-/-), PACAP and ApoE double-knockout mice (PACAP-/-/ApoE-/-) as well as PAC1 and ApoE double-knockout mice (PAC1-/-/ApoE-/-) which had been previously fed with a standard diet or a high cholesterol diet.
Compared to a standard diet (SD), a high cholesterol diet (HCD) led to a significant increase in the proportional area of astrocytes in the dentate gyrus of wildtype mice, but not in the number of astrocytes. The effect was found neither in the corpus callosum nor in the visual cortex, although generally, significant regional differences in astroglial signatures were observed. Notably, there was no significant effect of the genotype on astrocyte responses in SD or HCD.
Although replication is needed to confirm the results, our study provides further evidence of a cholesterol-induced astroglial response in the dentate gyrus and questions the role of PACAP and PAC1 in the pathophysiology of atherosclerosis-associated neuroinflammation in the brain. |
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| Umfang: | 76 Seiten |
| DOI: | 10.17192/z2023.0300 |