Neurochemical research, 2024-07, Vol.49 (7), p.1851-1862
2024
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- Autor(en) / Beteiligte
- Titel
- Changes in Astroglial Water Flow in the Pre-amyloid Phase of the STZ Model of AD Dementia
- Ist Teil von
- Neurochemical research, 2024-07, Vol.49 (7), p.1851-1862
- Ort / Verlag
- New York: Springer US
- Erscheinungsjahr
- 2024
- Quelle
- SpringerLink (Online service)
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0364-3190, 1573-6903eISSN: 1573-6903DOI: 10.1007/s11064-024-04144-6Titel-ID: cdi_proquest_miscellaneous_3053980655
- Format
- –
- Schlagworte
- Alzheimer Disease - metabolism, Alzheimer Disease - pathology, Alzheimer's disease, Amyloid, Animals, Aquaporin 4, Aquaporin 4 - metabolism, Astrocytes, Astrocytes - metabolism, Biochemistry, Biomedical and Life Sciences, Biomedicine, Blood-brain barrier, Blood-Brain Barrier - metabolism, Brain damage, Brain injury, Calpain, Cell Biology, Cerebrospinal fluid, Cognitive ability, Connexin 43, Connexin 43 - metabolism, Dementia disorders, Disease Models, Animal, Economic impact, Glial fibrillary acidic protein, Hippocampus, Hippocampus - metabolism, Hypometabolism, Intracerebroventricular administration, Male, Neurochemistry, Neurodegenerative diseases, Neurology, Neurosciences, Original Paper, Proteins, Proteolysis, Rats, Rats, Wistar, Streptozocin, Water - metabolism, Water flow