931 Hepatic Mitochondria Obtained From 6-Ohda-Lesioned Parkinsonian Rats Exhibit Decreased Energy Capacity and Membrane Potential

Vairetti, Mariapia; Ferrigno, Andrea; Rizzo, V.; Ambrosi, Giulia; Bianchi, Alberto; Richelmi, Plinio; Blandini, Fabio; Armentero, Marie Thérèse

doi:10.1016/s0168-8278(10)60932-4

Cited by 2 publications

(3 citation statements)

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“…These stimuli range from inflammatory responses sent from the spleen (65) to regulation of nutrient metabolism through signals from the gut microbiota (66). In mammals, alterations to the brain-liver axis have been implicated in several models of neurodegenerative disease (67)(68)(69)(70). For example, in mice models of Parkinson's disease, nigrostriatal degeneration results in hepatic mitochondrial dysfunction, causing metabolic dysregulation that selfperpetuates initial neurodegenerative symptoms (68).…”

Section: Discussionmentioning

confidence: 99%

“…In mammals, alterations to the brain-liver axis have been implicated in several models of neurodegenerative disease (67)(68)(69)(70). For example, in mice models of Parkinson's disease, nigrostriatal degeneration results in hepatic mitochondrial dysfunction, causing metabolic dysregulation that selfperpetuates initial neurodegenerative symptoms (68). Reversals of candidate genes and pathways within this brain-liver axis, however, indicate these processes in the shrew are selfperpetuating.…”

Section: Discussionmentioning

confidence: 99%

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Molecular mechanisms of seasonal brain shrinkage and regrowth inSorex araneus

Thomas,

Dechmann,

Nieland

et al. 2023

Preprint

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Human brains typically grow through development, then remain the same size in adulthood, and often shrink through age-related degeneration that induces cognitive decline and impaired functionality. In most cases, however, the neural and organismal changes that accompany shrinkage, especially early in the process, remain unknown. Paralleling neurodegenerative phenotypes, the Eurasian common shrewSorex araneus, shrinks its brain in autumn through winter, but then reverses this process by rapidly regrowing the brain come spring. To identify the molecular underpinnings and parallels to human neurodegeneration of this unique brain size change, we analyzed multi-organ, season-specific transcriptomics and metabolomic data. Simultaneous with brain shrinkage, we discovered system-wide metabolic shifts from lipid to glucose metabolism, as well as neuroprotection of brain metabolic homeostasis through reduced cholesterol efflux. These mechanisms rely on a finely tuned brain-liver crosstalk that results in changes in expression of human markers of aging and neurodegeneration in Parkinson’s disease and Huntington’s disease. We propose metabolic shifts with signals that cross the brain blood barrier are central to seasonal brain size changes inS. araneus, with potential implications for therapeutic treatment of human neurodegeneration.Significance StatementMetabolic regulation has been implicated in altered brain size and function, but the processes that parallel brain shrinkage remain unknown.Sorex araneus, the Eurasian common shrew, maintains activity throughout the winter through seasonal brain size plasticity, known as Dehnel’s phenomenon. Using this predictable, natural model of brain size change, we generated and analyzed multi-omics data across organs that undergo seasonal size change to characterize underlying molecular mechanisms. Results implicate drastic metabolic shifts and coordinated brain-liver crosstalk in seasonal size change, highlighting the relationship between metabolism, aging, and neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of seasonal brain shrinkage and regrowth inSorex araneus

Thomas,

Dechmann,

Nieland

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Together, those results indicated a brain-liver crosstalk is a pivotal avenue of communication to coordinate metabolic modifications underlying seasonal size change across organs. Although disruption of the brain-liver axis has been implicated in neurodegenerative diseases in other mammals (25)(26)(27)(28), how a highly functional brain-liver crosstalk which coordinates the shrew's natural seasonal size change operates and evolved remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Seasonal and comparative evidence of adaptive gene expression in mammalian brain size plasticity

Thomas,

Richter,

O’Neil

et al. 2024

Preprint

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Contrasting almost all other mammalian wintering strategies, Eurasian common shrews,Sorex araneus, endure winter by shrinking their brain, skull, and most organs, only to then regrow to breeding size the following spring. How such tiny mammals achieve this unique brain size plasticity while maintaining activity through the winter remains unknown. To discover potential adaptations underlying this trait, we analyzed seasonal differential expression in the shrew hypothalamus, a brain region that both regulates metabolic homeostasis and drastically changes size and compared hypothalamus expression across species. We discovered seasonal variation in suites of genes involved in energy homeostasis and apoptosis, shrew-specific upregulation of genes involved in the development of the hypothalamic blood brain barrier and calcium signaling, as well as overlapping seasonal and comparative gene expression divergence in genes implicated in the development and progression of human neurological and metabolic disorders, includingCCDC22,FAM57B, andGPR3. With high metabolic rates and facing harsh winter conditions,Sorex araneushave evolved both adaptive and plastic mechanisms to sense and regulate its energy budget. Many of these expression changes mirrored those identified in human neurological and metabolic disease, highlighting the interactions between metabolic homeostasis, brain size plasticity, and longevity.

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931 Hepatic Mitochondria Obtained From 6-Ohda-Lesioned Parkinsonian Rats Exhibit Decreased Energy Capacity and Membrane Potential

Cited by 2 publications

References 0 publications

Molecular mechanisms of seasonal brain shrinkage and regrowth inSorex araneus

Molecular mechanisms of seasonal brain shrinkage and regrowth inSorex araneus

Seasonal and comparative evidence of adaptive gene expression in mammalian brain size plasticity

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