Alzheimer's disease (AD) represents an urgent yet unmet challenge for modern society, calling for exploration of innovative targets and therapeutic approaches. Astrocytes, main homeostatic cells in the CNS, represent promising cell-target. Our aim was to investigate if deletion of the regulatory CaNB1 subunit of calcineurin in astrocytes could mitigate AD-related memory deficits, neuropathology, and neuroinflammation. We have generated two, acute and chronic, AD mouse models with astrocytic CaNB1 ablation (ACN-KO). In the former, we evaluated the ability of β-amyloid oligomers (AβOs) to impair memory and activate glial cells once injected in the cerebral ventricle of conditional ACN-KO mice. Next, we generated a tamoxifen-inducible astrocyte-specific CaNB1 knock-out in 3xTg-AD mice (indACNKO-AD). CaNB1 was deleted, by tamoxifen injection, in 11.7-month-old 3xTg-AD mice for 4.4 months. Spatial memory was evaluated using the Barnes maze; β-amyloid plaques burden, neurofibrillary tangle deposition, reactive gliosis, and neuroinflammation were also assessed. The acute model showed that ICV injected AβOs in 2-month-old wild type mice impaired recognition memory and fostered a pro-inflammatory microglia phenotype, whereas in ACN-KO mice, AβOs were inactive. In indACNKO-AD mice, 4.4 months after CaNB1 depletion, we found preservation of spatial memory and cognitive flexibility, abolishment of amyloidosis, and reduction of neurofibrillary tangles, gliosis, and neuroinflammation. Our results suggest that ACN is crucial for the development of cognitive impairment, AD neuropathology, and neuroinflammation. Astrocyte-specific CaNB1 deletion is beneficial for both the abolishment of AβO-mediated detrimental effects and treatment of ongoing AD-related pathology, hence representing an intriguing target for AD therapy.
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http://dx.doi.org/10.1002/glia.24509 | DOI Listing |
Cell Mol Neurobiol
December 2024
Laboratory of Veterinary Biochemistry, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, 63243, South Korea.
Chronic exposure to prenatal stress can impair neurogenesis and lead to irreversible cognitive and neuropsychiatric abnormalities in offspring. The retina is part of the nervous system; however, the impacts of prenatal stress on retinal neurogenesis and visual function remain unclear. This study examined how elevated prenatal glucocorticoid levels differentially affect retinal development in the offspring of pregnant mice exposed to chronic unpredictable mild stress (CUMS).
View Article and Find Full Text PDFMetab Brain Dis
December 2024
Department of Basic Science, School of Science and Technology, Babcock University, Ilishan-Remo, Ogun State, Nigeria.
Diabetes Mellitus is a metabolic disorder characterized by high blood glucose levels, causing significant morbidity and mortality rates. This study investigated the antidiabetic, neuroprotective, and antioxidant effects of ethanol extracts of Parkia biglobosa (PB) leaves and seeds in streptozotocin (STZ)-induced diabetic rats. The administration of STZ significantly elevated fasting blood glucose levels (FBGL) to 355-400 mg/mL compared to 111 mg/mL in normal controls, indicating hyperglycemia.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Nanyang Technological University, School of Chemistry, Chemical Engineering and Biotechnology, 21 Nanyang Link, 637371, Singapore, SINGAPORE.
Microglial phagocytosis is a highly energy-consuming process that plays critical roles in clearing neurotoxic amyloid-β (Aβ) in Alzheimer's disease (AD). However, microglial metabolism is defective overall in AD, thereby undermining microglial phagocytic functions. Herein, we repurpose the existing antineoplastic drug lonidamine (LND) conjugated with hollow mesoporous Prussian blue (HMPB) as a "microglial energy modulator" (termed LND@HMPB-T7) for safe and synergistic Aβ clearance.
View Article and Find Full Text PDFCardiol Rev
December 2024
Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY.
Systemic hypertension is possibly the most important modifiable risk factor for the development of cognitive decline, both for mild cognitive impairment (MCI) and dementia. For effective blood pressure (BP) control, it requires proper assessment, using brachial, central, and ambulatory measurements, and monitoring with a focus on different BP parameters. Different BP parameters like pulse pressure, mean arterial pressure, BP variability, and circadian parameters, like nondippers and early morning surge, should be considered in the evaluation for the risk of cognitive decline due to hypertension in middle age and older adults.
View Article and Find Full Text PDFJMIR Aging
December 2024
Clinical Research, Telemedicine and Telepharmacy Centre, School of Medicinal and Health Products Sciences, University Camerino, Camerino, Italy.
Background: To diagnose Alzheimer disease (AD), individuals are classified according to the severity of their cognitive impairment. There are currently no specific causes or conditions for this disease.
Objective: The purpose of this systematic review and meta-analysis was to assess AD prevalence across different stages using machine learning (ML) approaches comprehensively.
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