Changes in Astroglial Water Flow in the Pre-amyloid Phase of the STZ Model of AD Dementia.

Autor: Gayger-Dias V; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Menezes L; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Da Silva VF; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Stiborski A; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Silva ACR; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Sobottka TM; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Quines-Silva VC; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Pakulski-Souto B; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Bobermin LD; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil.; Graduate Program in Neurosciences, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Quincozes-Santos A; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil.; Graduate Program in Neurosciences, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Leite MC; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil., Gonçalves CA; Biochemistry Laboratory 33, Graduate Program in Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil. casg@ufrgs.br.; Graduate Program in Neurosciences, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos Street, 2600, Porto Alegre, 90035-003, Brazil. casg@ufrgs.br.
Jazyk: angličtina
Zdroj: Neurochemical research [Neurochem Res] 2024 Jul; Vol. 49 (7), pp. 1851-1862. Date of Electronic Publication: 2024 May 11.
DOI: 10.1007/s11064-024-04144-6
Abstrakt: Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that is typically sporadic and has a high social and economic cost. We utilized the intracerebroventricular administration of streptozotocin (STZ), an established preclinical model for sporadic AD, to investigate hippocampal astroglial changes during the first 4 weeks post-STZ, a period during which amyloid deposition has yet to occur. Astroglial proteins aquaporin 4 (AQP-4) and connexin-43 (Cx-43) were evaluated, as well as claudins, which are tight junction (TJ) proteins in brain barriers, to try to identify changes in the glymphatic system and brain barrier during the pre-amyloid phase. Glial commitment, glucose hypometabolism and cognitive impairment were characterized during this phase. Astroglial involvement was confirmed by an increase in glial fibrillary acidic protein (GFAP); concurrent proteolysis was also observed, possibly mediated by calpain. Levels of AQP-4 and Cx-43 were elevated in the fourth week post-STZ, possibly accelerating the clearance of extracellular proteins, since these proteins actively participate in the glymphatic system. Moreover, although we did not see a functional disruption of the blood-brain barrier (BBB) at this time, claudin 5 (present in the TJ of the BBB) and claudin 2 (present in the TJ of the blood-cerebrospinal fluid barrier) were reduced. Taken together, data support a role for astrocytes in STZ brain damage, and suggest that astroglial dysfunction accompanies or precedes neuronal damage in AD.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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