The Aged Striatum: Evidence of Molecular and Structural Changes Using a Longitudinal Multimodal Approach in Mice

Giacobbo, Bruno Lima; Özalay, Özgün; Mediavilla, Tomás; Ericsson, Madelene; Axelsson, Jan; Rieckmann, Anna; Sultan, Fahad; Marcellino, Daniel

doi:10.3389/fnagi.2022.795132

Cited by 4 publications

(8 citation statements)

References 53 publications

(65 reference statements)

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“…Several studies have demonstrated the significance of DA signalling in the maintenance of motor function, and that declines in dopamine functional component availability might be responsible for age-related behavioural deficits [50][51][52][53][54]. In the treated group, the gene expression of DA markers demonstrated an overall increase compared to that in aged rats.…”

Section: Discussionmentioning

confidence: 97%

“…The impact of age on several DA targets, including receptors, transporters, and relevant enzymes in the striatum, has been reported [50][51][52][53][54]. Gene expression of the main functional components of DA neurones was assessed in the different groups.…”

Section: Bmmscs Restored Da System Functionmentioning

confidence: 99%

“…Several reports have shown that pathogenic alterations associated with PD are identical to agerelated changes in DA neurones. The loss of DA neurones in the substantia nigra (SN), which reduces the amount of dopamine released and the number of DA receptors in the striatum and causes bradykinesia, muscular stiffness, and shaking, is a notable neuropathological aspect of PD [5][6][7][8][9]. These characteristics are mostly related to ageing (also known as late-onset PD) and are dependent on environmental and hereditary variables [10].…”

Section: Introductionmentioning

confidence: 99%

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Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats

El–Akabawy

Kersh²,

Rashed³

et al. 2023

Folia Morphol

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Section: Discussionmentioning

confidence: 97%

Section: Bmmscs Restored Da System Functionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats

El–Akabawy

Kersh²,

Rashed³

et al. 2023

Folia Morphol

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“…One of the most significant observations from these novel experiments is the shift in motivation between 6- and 12-months of age in both C- and HF-fed offspring. Aging is associated with reduced food cravings in humans [ 62 ] and decreased motivation and reduced striatal D2R availability in male C57Bl/6 mice [ 63 , 64 , 65 , 66 ]. Thus, the shift towards decreased motivation in the 12-month-old C/C male mice is consistent with a natural age-related decline.…”

Section: Discussionmentioning

confidence: 99%

Appetitive Motivation and Associated Neurobiology Change Differentially across the Life Course of Mouse Offspring Exposed to Peri- and Postnatal High Fat Feeding

2022

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Alterations in neural pathways that regulate appetitive motivation may contribute to increased obesity risk in offspring born to mothers fed a high fat (HF) diet. However, current findings on the impact of maternal obesity on motivation in offspring are inconclusive, and there is no information about the long-lasting effects in aged animals. This study examined the longitudinal effect of perinatal and chronic postnatal HF intake on appetitive motivation in young and aged offspring. Female C57Bl/6 were fed either a control (C) or HF diet before mating through to lactation. At weaning, offspring were maintained on the C or HF diet, generating the following four diet groups: C/C, C/HF, HF/C, and HF/HF based on the pre/post weaning diet. At 6 months, motivation was higher in HF/C females, but lower in male and female C/HF and HF/HF mice. By 12 months, this difference was lost, as C-fed animals became less motivated, while motivation increased in HF-fed mice. The mRNA levels of dopamine receptor 1 and 2 increased with age, while cannabinoid receptor 1 and μ-opioid receptor expression remained stable or decreased in mesolimbic and mesocortical dopaminergic pathways. Results from this study suggest that perinatal and chronic postnatal HF feeding produced opposite effects on appetitive motivation in young adult offspring mice, which was also reflected in the shift in motivation over time. These results have significant implications for patterns of hedonic eating across the life course and the relative risk of obesity at different time points.

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“…The three cohorts underwent functional and structural MRI in three batches. Males of the first ( n = 9) and third ( n = 8) cohorts also underwent PET/CT experiments 48 . A summary of all animals and their functional MRI sessions (12-24 motnhs) are listed in Supplementary Data 2 .…”

Section: Methodsmentioning

confidence: 99%

Longitudinal monitoring of the mouse brain reveals heterogenous network trajectories during aging

Özalay,

Mediavilla,

Giacobbo

et al. 2024

Commun Biol

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The human aging brain is characterized by changes in network efficiency that are currently best captured through longitudinal resting-state functional MRI (rs-fMRI). These studies however are challenging due to the long human lifespan. Here we show that the mouse animal model with a much shorter lifespan allows us to follow the functional network organization over most of the animal’s adult lifetime. We used a longitudinal study of the functional connectivity of different brain regions with rs-fMRI under anesthesia. Our analysis uncovers network modules similar to those reported in younger mice and in humans (i.e., prefrontal/default mode network (DMN), somatomotor and somatosensory networks). Statistical analysis reveals different patterns of network reorganization during aging. Female mice showed a pattern akin to human aging, with de-differentiation of the connectome, mainly due to increases in connectivity of the prefrontal/DMN cortical networks to other modules. Our male cohorts revealed heterogenous aging patterns with only one group confirming the de- differentiation, while the majority showed an increase in connectivity of the somatomotor cortex to the Nucleus accumbens. In summary, in line with human work, our analysis in mice supports the concept of de-differentiation in the aging mammalian brain and reveals additional trajectories in aging mice networks.

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The Aged Striatum: Evidence of Molecular and Structural Changes Using a Longitudinal Multimodal Approach in Mice

Cited by 4 publications

References 53 publications

Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats

Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats

Appetitive Motivation and Associated Neurobiology Change Differentially across the Life Course of Mouse Offspring Exposed to Peri- and Postnatal High Fat Feeding

Longitudinal monitoring of the mouse brain reveals heterogenous network trajectories during aging

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