Aging in the cerebellum and hippocampus and associated behaviors over the adult life span of CB6F1 mice

Kennard, John A.; Brown, Kevin L.; Woodruff-Pak, Diana S.

doi:10.1016/j.neuroscience.2013.06.002

Cited by 9 publications

(4 citation statements)

References 124 publications

(150 reference statements)

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“…Aging is an intrinsic and complex biological process that is characterized by structural degeneration and functional decline, progressively leading to aging-related diseases, such as neurodegenerative diseases in humans, including Parkinson's disease, trinucleotide repeat disorders, and Alzheimer's disease (Morrison and Hof, 1997 ; Kennard and Woodruff-Pak, 2011 ; Kennard et al, 2013 ; Lopez-Otin et al, 2013 ; Kennedy et al, 2014 ). Of a variety of genetic and environmental factors that can influence the aging process, altered epigenetic landscapes have been well-documented during aging (Calvanese et al, 2009 ; Vlaming and Van Leeuwen, 2012 ; Huidobro et al, 2013 ; Booth and Brunet, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Brain Region- and Age-Dependent 5-Hydroxymethylcytosine Activity in the Non-Human Primate

Zhong

Wei

et al. 2022

Front. Aging Neurosci.

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Because of the difficulty in collecting fresh brains of humans at different ages, it remains unknown how epigenetic regulation occurs in the primate brains during aging. In the present study, we examined the genomic distribution of 5hmC, an indicator of DNA methylation, in the brain regions of non-human primates (rhesus monkey) at the ages of 2 (juvenile), 8 (young adult), and 17 (old) years. We found that genomic 5hmC distribution was accumulated in the monkey brain as age increased and displayed unique patterns in the cerebellum and striatum in an age-dependent manner. We also observed a correlation between differentially hydroxymethylated regions (DhMRs) and genes that contribute to brain region-related functions and diseases. Our studies revealed, for the first time, the brain-region and age-dependent 5hmC modifications in the non-human primate and the association of these 5hmC modifications with brain region-specific function and potentially aging-related brain diseases.

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Section: Introductionmentioning

confidence: 99%

Brain Region- and Age-Dependent 5-Hydroxymethylcytosine Activity in the Non-Human Primate

Zhong

Wei

et al. 2022

Front. Aging Neurosci.

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“…Most stereological investigations on the cerebellum involving laboratory animals have been carried out on mice (Kennard et al, 2013; Song et al, 2014; Wittmann & McLennan, 2011; Woodruff‐Pak, 2006; Woodruff‐Pak et al, 2010), rats (Korbo et al, 1993; Larsen et al, 1993, 2000; Ragbetli et al, 2007; Sonmez et al, 2010), and rabbits (Akosman et al, 2011; Selçuk & Tıpırdamaz, 2020), but also on domestic animals such as cats (Sadeghinezhad et al, 2020), pigs (Jelsing et al, 2006), and chicks (Tunç et al, 2006). Apart from a stereological study performed on prenatal and neonatal guinea‐pig cerebella following experimentally induced intrauterine growth restriction (Mallard et al, 2000), the morphometric features of the normal cerebellum in adult animals of this species have not been previously investigated using stereological techniques.…”

Section: Introductionmentioning

confidence: 99%

Design‐based stereological study of the guinea‐pig (Cavia porcellus) cerebellum

et al. 2021

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Guinea pigs have proved useful as experimental animal models in studying cerebellar anatomical and structural alterations in human neurological disease; however, they are also currently acquiring increasing veterinary interest as companion animals. The morphometric features of the normal cerebellum in guinea pigs have not been previously investigated using stereology. The objective of the present work was to establish normal volumetric and quantitative stereological parameters for cerebellar tissues in guinea pigs, by means of unbiased design‐based stereology. Cerebellar total volume, gray and white matter volume fractions, molecular and granular layers volume fractions, cerebellar surface area, Purkinje cellular and nuclear volumes, and the Purkinje cell total count were stereologically estimated. For this purpose, cerebellar hemispheres from six adult male guinea pigs were employed. Isotropic, uniform random sections were obtained by applying the orientator method, and subsequently processed for light microscopy. The cerebellar total volume, the white and grey matter volume fractions, and the molecular and granular layer volumes were estimated using the Cavalieri's principle and the point counting system. The cerebellar surface area was estimated through the use of test lines; Purkinje cellular and nuclear volumes were analysed using the nucleator technique, whereas the Purkinje cell total count was obtained by means of the optical disector technique. The mean ± standard deviation total volume of a guinea‐pig cerebellar hemisphere was 0.11 ± 0.01 cm3. The mean volumetric proportions occupied by the gray and white matters were, respectively, 78.0 ± 2.6% and 22.0 ± 2.6%, whereas their mean absolute volumes were found to be 0.21 ± 0.02 cm3 and 0.059 ± 0.006 cm3. The volumes of the molecular and granular layers were estimated at 112.4 ± 20.6 mm3 and 104.4 ± 7.3 mm3, whereas their mean thicknesses were calculated to be 0.184 ± 0.020 mm and 0.17 ± 0.02 mm. The molecular and granular layers accounted for 40.7 ± 3.9% and 37.4 ± 1.8% of total cerebellar volume respectively. The surface area of the cerebellum measured 611.4 ± 96.8 mm2. Purkinje cells with a cellular volume of 3210.1 µm3 and with a nuclear volume of 470.9 µm3 had a higher incidence of occurrence. The mean total number of Purkinje cells for a cerebellar hemisphere was calculated to be 253,090 ± 34,754. The morphometric data emerging from the present study provide a set of reference data which might prove valuable as basic anatomical contribution for practical applications in veterinary neurology.

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“…At the cellular level, aging is not linked to an overall reduction in the amount of pre-existing neurons in the central nervous system, although certain brain structures and neuronal subtypes may be more vulnerable than others and selectively prone to cell loss [1,2]. For example, age-related neuronal death has been described in specific subpopulations of the cerebral cortex and the cerebellum [3,4]. The strongest effects of aging, however, appear to be exerted at the level of synaptic activity, as shown by the age-associated decline in the number of synapses and in synaptic plasticity in several brain regions [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Molecular Signatures of the Aging Brain: Finding the Links Between Genes and Phenotypes

et al. 2019

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Aging is associated with cognitive decline and increased vulnerability to neurodegenerative diseases. The progressive extension of the average human lifespan is bound to lead to a corresponding increase in the fraction of cognitively impaired elderly individuals among the human population, with an enormous societal and economic burden. At the cellular and tissue levels, cognitive decline is linked to a reduction in specific neuronal subpopulations, a widespread decrease in synaptic plasticity and an increase in neuroinflammation due to an enhanced activation of astrocytes and microglia, but the molecular mechanisms underlying these functional changes during normal aging and in neuropathological conditions remain poorly understood. In this review, we summarize very recent and outstanding progress in elucidating the molecular changes associated with cognitive decline through the genome-wide profiling of aging brain cells at different molecular levels (genomic, epigenomic, transcriptomic, proteomic). We discuss how the correlation of different molecular and phenotypic traits driven by mathematical and computational analyses of large datasets has led to the prediction of key molecular nodes of neurodegenerative pathways, and provide a few examples of candidate regulators of cognitive decline identified with these approaches. Furthermore, we highlight the dysregulation of the synaptic transcriptome in neuronal cells and of the inflammatory transcriptome in glial cells as some of the key events during normal and neuropathological human brain aging.

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Aging in the cerebellum and hippocampus and associated behaviors over the adult life span of CB6F1 mice

Cited by 9 publications

References 124 publications

Brain Region- and Age-Dependent 5-Hydroxymethylcytosine Activity in the Non-Human Primate

Brain Region- and Age-Dependent 5-Hydroxymethylcytosine Activity in the Non-Human Primate

Design‐based stereological study of the guinea‐pig (Cavia porcellus) cerebellum

Molecular Signatures of the Aging Brain: Finding the Links Between Genes and Phenotypes

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