Decreased Glucose Metabolism and Glutamine Synthesis in the Retina of a Transgenic Mouse Model of Alzheimer’s Disease

Tams, Anna Luna Mølgaard; Sanz-Morello, Berta; Westi, Emil W.; Mouhammad, Zaynab Ahmad; Andersen, Jens V.; Freude, Kristine; Vohra, Rupali; Hannibal, Jens; Aldana, Blanca I.; Kolko, Miriam

doi:10.1007/s10571-021-01126-y

Cited by 5 publications

(8 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While there are no studies, to the best of our knowledge, that directly compares GS changes in the AD eye and brain, previous studies have shown conflicting evidence of GS levels in the AD brain. Most studies showed a decrease in GS activity and levels in AD, including in the post-mortem human brain and transgenic mouse models [7,39,41,58,67,68,80]. Other studies showed an increase of GS in the prefrontal cortex and cerebrospinal fluid [6,82].…”

Section: Metabolic Decline Of Müller Cells In Ad Retinamentioning

confidence: 99%

Müller cell degeneration and microglial dysfunction in the Alzheimer’s retina

Boerkoel

Hirsch‐Reinshagen

et al. 2022

acta neuropathol commun

View full text Add to dashboard Cite

Amyloid beta (Aβ) deposits in the retina of the Alzheimer’s disease (AD) eye may provide a useful diagnostic biomarker for AD. This study focused on the relationship of Aβ with macroglia and microglia, as these glial cells are hypothesized to play important roles in homeostasis and clearance of Aβ in the AD retina. Significantly higher Aβ load was found in AD compared to controls, and specifically in the mid-peripheral region. AD retina showed significantly less immunoreactivity against glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) compared to control eyes. Immunoreactivity against ionized calcium binding adapter molecule-1 (IBA-1), a microglial marker, demonstrated a higher level of microgliosis in AD compared to control retina. Within AD retina, more IBA-1 immunoreactivity was present in the mid-peripheral retina, which contained more Aβ than the central AD retina. GFAP co-localized rarely with Aβ, while IBA-1 co-localized with Aβ in more layers of control than AD donor retina. These results suggest that dysfunction of the Müller and microglial cells may be key features of the AD retina.

show abstract

Section: Metabolic Decline Of Müller Cells In Ad Retinamentioning

confidence: 99%

Müller cell degeneration and microglial dysfunction in the Alzheimer’s retina

Boerkoel

Hirsch‐Reinshagen

et al. 2022

acta neuropathol commun

View full text Add to dashboard Cite

show abstract

“…Cerebral glucose hypometabolism has been used as an early-stage biomarker prior to the onset of clinical symptoms in patients with AD (Mosconi et al, 2008a ; Bulleid, 2012 ; Johnson et al, 2020 ; Lu et al, 2020 ; Tams et al, 2021 ; Zhang et al, 2021 ). Notably, the stimulation of brain glucose uptake is able to delay AD pathological decline and results in an improvement in cognitive tests, further reinforcing the idea that glucose metabolism in the brain is a fundamental process that is altered in patients with AD (Winkler et al, 2015 ; Gejl et al, 2017 ; Lee et al, 2019 ; Minhas et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Disruption of Glucose Metabolism in Aged Octodon degus: A Sporadic Model of Alzheimer's Disease

Cisternas

Gherardelli

Salazar

et al. 2021

Front. Integr. Neurosci.

View full text Add to dashboard Cite

Alzheimer's disease is a progressive neurodegenerative disorder and the most common cause of dementia. Although transgenic Alzheimer's disease (AD) animal models have greatly contributed to our understanding of the disease, therapies tested in these animals have resulted in a high rate of failure in preclinical trials for AD. A promising model is Octodon degus (degu), a Chilean rodent that spontaneously develops AD-like neuropathology. Previous studies have reported that, during aging, degus exhibit a progressive decline in cognitive function, reduced neuroinflammation, and concomitant increases in the number and size of amyloid β (Aβ) plaques in several brain regions. Importantly, in humans and several AD models, a correlation has been shown between brain dysfunction and neuronal glucose utilization impairment, a critical aspect considering the high-energy demand of the brain. However, whether degus develop alterations in glucose metabolism remains unknown. In the present work, we measured several markers of glucose metabolism, namely, glucose uptake, ATP production, and glycolysis and pentose phosphate pathway (PPP) flux, in hippocampal slices from degus of different ages. We found a significant decrease in hippocampal glucose metabolism in aged degus, caused mainly by a drop in glucose uptake, which in turn, reduced ATP synthesis. Moreover, we observed a negative correlation between age and PPP flux. Together, our data further support the use of degus as a model for studying the neuropathology involved in sporadic AD-like pathology and as a potentially valuable tool in the search for effective treatments against the disease.

show abstract

“…Under normal physiological function, the reactive species generated can be controlled by antioxidant defenses [17]. However, in the early stages of AD, oxidative stress is present, and glia and neurons are highly sensitive to this [17], as brain cells respond to oxidative stress, they enter a cycle of increased ROS generation, causing more oxidative stress and mitochondrial damage, ultimately leading to cell death [18,19].…”

Section: Introductionmentioning

confidence: 99%

Potential Retinal Biomarkers in Alzheimer’s Disease

García-Bermúdez,

Vohra,

Freude

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Alzheimer’s disease (AD) represents a major diagnostic challenge, as early detection is crucial for effective intervention. This review examines the diagnostic challenges facing current AD evaluations and explores the emerging field of retinal alterations as early indicators. Recognizing the potential of the retina as a noninvasive window to the brain, we emphasize the importance of identifying retinal biomarkers in the early stages of AD. However, the examination of AD is not without its challenges, as the similarities shared with other retinal diseases introduce complexity in the search for AD-specific markers. In this review, we address the relevance of using the retina for the early diagnosis of AD and the complex challenges associated with the search for AD-specific retinal biomarkers. We provide a comprehensive overview of the current landscape and highlight avenues for progress in AD diagnosis by retinal examination.

show abstract

Decreased Glucose Metabolism and Glutamine Synthesis in the Retina of a Transgenic Mouse Model of Alzheimer’s Disease

Cited by 5 publications

References 71 publications

Müller cell degeneration and microglial dysfunction in the Alzheimer’s retina

Müller cell degeneration and microglial dysfunction in the Alzheimer’s retina

Disruption of Glucose Metabolism in Aged Octodon degus: A Sporadic Model of Alzheimer's Disease

Potential Retinal Biomarkers in Alzheimer’s Disease

Contact Info

Product

Resources

About