Evidence of Energy Metabolism Alterations in Cultured Neonatal Astrocytes Derived from the Ts65Dn Mouse Model of Down Syndrome

For many decades, neurons have been the central focus of studies on the mechanisms underlying the neurodevelopmental and neurodegenerative aspects of Down syndrome (DS). Astrocytes, which were once thought to have only a passive role, are now recognized as active participants of a variety of essential physiological processes in the brain. Alterations in their physiological function have, thus, been increasingly acknowledged as likely initiators of or contributors to the pathogenesis of many nervous system disorders and diseases. In this study, we carried out a series of real-time measurements of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in hippocampal astrocytes derived from neonatal Ts65Dn and euploid control mice using a Seahorse XFp Flux Analyzer. Our results revealed a significant basal OCR increase in neonatal Ts65Dn astrocytes compared with those from control mice, indicating increased oxidative phosphorylation. ECAR did not differ between the groups. Given the importance of astrocytes in brain metabolic function and the linkage between astrocytic and neuronal energy metabolism, these data provide evidence against a pure “neurocentric” vision of DS pathophysiology and support further investigations on the potential contribution of disturbances in astrocytic energy metabolism to cognitive deficits and neurodegeneration associated with DS.

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Long-term voluntary running modifies the levels of proteins of the excitatory/inhibitory system and reduces reactive astrogliosis in the brain of Ts65Dn mouse model for Down syndrome

Brain Research ◽

10.1016/j.brainres.2021.147535 ◽

2021 ◽

pp. 147535

Author(s):

Elizabeth Kida ◽

Marius Walus ◽

Giorgio Albertini ◽

Adam A. Golabek

Keyword(s):

Down Syndrome ◽

Mouse Model ◽

Ts65dn Mouse ◽

Inhibitory System ◽

Reactive Astrogliosis ◽

Voluntary Running ◽

The Brain

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The BACH1/Nrf2 Axis in Brain in Down Syndrome and Transition to Alzheimer Disease-Like Neuropathology and Dementia

Antioxidants ◽

10.3390/antiox9090779 ◽

2020 ◽

Vol 9 (9) ◽

pp. 779

Author(s):

Marzia Perluigi ◽

Antonella Tramutola ◽

Sara Pagnotta ◽

Eugenio Barone ◽

D. Allan Butterfield

Keyword(s):

Down Syndrome ◽

Senile Plaques ◽

Redox Homeostasis ◽

Antioxidant Defense System ◽

Chromosome 21 ◽

Potential Contribution ◽

Physiological Relevance ◽

Increased Risk ◽

Hyperphosphorylated Tau Protein ◽

The Brain

Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses. Published studies from our laboratories propose that increased oxidative damage occurs early in life in DS population and contributes to age-dependent neurodegeneration. This is the result of damaged, oxidized proteins that belong to degradative systems, antioxidant defense system, neuronal trafficking. and energy metabolism. This review focuses on a key element that regulates redox homeostasis, the transcription factor Nrf2, which is negatively regulated by BACH1, encoded on chromosome 21. The role of the Nrf2/BACH1 axis in DS is under investigation, and the effects of triplicated BACH1 on the transcriptional regulation of Nrf2 are still unknown. In this review, we discuss the physiological relevance of BACH1/Nrf2 signaling in the brain and how the dysfunction of this system affects the redox homeostasis in DS neurons and how this axis may contribute to the transition of DS into DS with AD neuropathology and dementia. Further, some of the evidence collected in AD regarding the potential contribution of BACH1 to neurodegeneration in DS are also discussed.

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Morphological Changes in the Brain of Acutely Ill and Weight-Recovered Patients with Anorexia Nervosa

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie ◽

10.1024/1422-4917/a000265 ◽

2014 ◽

Vol 42 (1) ◽

pp. 7-18 ◽

Cited By ~ 56

Author(s):

Jochen Seitz ◽

Katharina Bühren ◽

Georg G. von Polier ◽

Nicole Heussen ◽

Beate Herpertz-Dahlmann ◽

...

Keyword(s):

Anorexia Nervosa ◽

Cognitive Deficits ◽

Time Course ◽

Morphological Changes ◽

Meta Analysis ◽

Short Term ◽

Clinical Prognosis ◽

Qualitative Review ◽

Brain Changes ◽

The Brain

Objective: Acute anorexia nervosa (AN) leads to reduced gray (GM) and white matter (WM) volume in the brain, which however improves again upon restoration of weight. Yet little is known about the extent and clinical correlates of these brain changes, nor do we know much about the time-course and completeness of their recovery. Methods: We conducted a meta-analysis and a qualitative review of all magnetic resonance imaging studies involving volume analyses of the brain in both acute and recovered AN. Results: We identified structural neuroimaging studies with a total of 214 acute AN patients and 177 weight-recovered AN patients. In acute AN, GM was reduced by 5.6% and WM by 3.8% compared to healthy controls (HC). Short-term weight recovery 2–5 months after admission resulted in restitution of about half of the GM aberrations and almost full WM recovery. After 2–8 years of remission GM and WM were nearly normalized, and differences to HC (GM: –1.0%, WM: –0.7%) were no longer significant, although small residual changes could not be ruled out. In the qualitative review some studies found GM volume loss to be associated with cognitive deficits and clinical prognosis. Conclusions: GM and WM were strongly reduced in acute AN. The completeness of brain volume rehabilitation remained equivocal.

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