Biology subjects

Kyle, M.

Publications and source records attributed to Kyle, M..

3 recordsLinked to original sources

bioRxiv2025

Structural Effects of Low Social Status and Obesogenic Diet on Social and Emotional Neurocircuits in Female Macaques: A Longitudinal Study from Infancy to Adulthood

A substantial body of literature has demonstrated a consistent link between psychosocial stress and obesity in children, particularly in those from low socioeconomic backgrounds. Despite evidence indicating a complex interplay between stress, diet and obesity, there is a limited understanding of the specific versus potentially synergistic effects of obesity and stress on brain structural and functional development. This study investigates the developmental and long-term brain structural alterations resulting from exposure to chronic social stress due to low (subordinate -SUB-) social status and postnatal obesogenic diets. Forty-one female rhesus macaques (Dominants -DOM-, n=21; Subordinates -SUB-, n=20) were assigned to either only low-calorie diet (LCD) or to both high-calorie diet (HCD) and LCD (Choice diet) from birth through the juvenile period. After menarche, all subjects were maintained on a LCD-only diet through adulthood. Twenty-seven animals (DOM: n=13, SUB: n=14) were studied again in adulthood to investigate the long-term effects of early diet and social rank on brain structure. Cumulative Kcal consumption was measured from birth through 16 months and body weights were measured at all time points. Overall, the findings show specific effects of obesogenic diet and psychosocial stress on cortical and corticolimbic brain regions. Animals with access to the obesogenic diet had larger overall brain size (measured as intracranial volume -ICV-) and larger overall volumes of prefrontal cortex, insula, superior temporal sulcus (defined as temporo-parieto-occipital area rostral and caudal regions (TPOr and TPOc)) than those in the low-calorie diet. Most of these regional diet effects, except for the insula, were driven by general effects of the diet on brain size. The diet effects were lost when adding the adult data to the longitudinal analysis, suggesting transient effects of obesogenic diets while the animals were consuming it, but not long-term, persistent effects. These findings highlight the potential of brain rescue mechanisms that could offset lasting developmental effects of early-life obesogenic diet consumption. With respect to social rank, SUB exhibited larger volumes in brain regions related to social cognition and emotional processing than DOM animals. When the adult data was added to the longitudinal analysis, the effects of social rank were prominent in the hippocampus, superior temporal sulcus, temporo-parieto-occipital rostral region, and the temporal auditory cortices after ICV data correction, suggesting long-term, persistent and cumulative effects of these social experiences, in contrast to the transient diet effects.

neuroscience↗

bioRxiv2024

Single cell RNA sequencing reveals immunomodulatory mechanism of stem cell factor and granulocyte colony-stimulating factor treatment in the brains of aged APP/PS1 mice

Alzheimers disease (AD) leads to progressive neurodegeneration and dementia. AD primarily affects older adults with neuropathological changes including amyloid-beta (A{beta}) deposition, neuroinflammation, and neurodegeneration. We have previously demonstrated that systemic treatment with combined stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF), reduces A{beta} load, increases A{beta} uptake by activated microglia and macrophages, reduces neuroinflammation, and restores dendrites and synapses in the brains of aged APPswe/PS1dE9 (APP/PS1) mice. However, the mechanisms underlying SCF+G-CSF-enhanced brain repair in aged APP/PS1 mice remain unclear. This study used a transcriptomic approach to identify potential mechanisms by which SCF+G-CSF treatment modulates microglia and peripheral myeloid cells to mitigate AD pathology in the aged brain. After injections of SCF+G-CSF for 5 consecutive days, single-cell RNA sequencing was performed on CD11b+ cells isolated from the brains of 28-month-old APP/PS1 mice. The vast majority of cell clusters aligned with transcriptional profiles of microglia in various activation states. However, SCF+G-CSF treatment dramatically increased a cell population showing upregulation of marker genes related to peripheral myeloid cells. Flow cytometry data also revealed an SCF+G-CSF-induced increase of cerebral CD45high/CD11b+ active phagocytes. SCF+G-CSF treatment robustly increased the transcription of genes implicated in immune cell activation, including gene sets that regulate inflammatory processes and cell migration. Expression of S100a8 and S100a9 were robustly enhanced following SCF+G-CSF treatment in all CD11b+ cell clusters. Moreover, the topmost genes differentially expressed with SCF+G-CSF treatment were largely upregulated in S100a8/9-positive cells, suggesting a well-conserved transcriptional profile related to SCF+G-CSF treatment in resident and peripherally derived CD11b+ immune cells. This S100a8/9-associated transcriptional profile contained notable genes related to pro-inflammatory and anti-inflammatory responses, neuroprotection, and A{beta} plaque inhibition or clearance. Altogether, this study reveals immunomodulatory effects of SCF+G-CSF treatment in the aged brain with AD pathology, which will guide future studies to further uncover the therapeutic mechanisms.

neuroscience↗

bioRxiv2023

Stem cell factor and granulocyte colony-stimulating factor promote remyelination in the chronic phase of severe traumatic brain injury

Severe traumatic brain injury (TBI) causes long-term disability and death in young adults. White matter is vulnerable to TBI damage. Demyelination is a major pathological change of white matter injury after TBI. Demyelination which is characterized by myelin sheath disruption and oligodendrocyte cell death leads to long-term neurological function deficits. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) treatments have shown neuroprotective and neurorestorative effects in the subacute and chronic phases of experimental TBI. Our previous study has revealed that combined SCF and G-CSF treatment (SCF+G-CSF) enhances myelin repair in the chronic phase of TBI. However, the long-term effect and mechanism of SCF+G-CSF-enhanced myelin repair remain unclear. In this study, we uncovered persistent and progressive myelin loss in the chronic phase of severe TBI. SCF+G-CSF treatment in the chronic phase of severe TBI enhanced remyelination in the ipsilateral external capsule and striatum. The SCF+G-CSF-enhanced myelin repair is positively correlated with the proliferation of oligodendrocyte progenitor cells in the subventricular zone. These findings reveal the therapeutic potential of SCF+G-CSF in myelin repair in the chronic phase of severe TBI and shed light on the mechanism underlying SCF+G-CSF-enhanced remyelination in chronic TBI.

neuroscience↗