Kitty Reemst - Academia.edu (original) (raw)
Papers by Kitty Reemst
Early-life stress (ELS) exposure increases the risk for mental disorders, including cognitive imp... more Early-life stress (ELS) exposure increases the risk for mental disorders, including cognitive impairments later in life. We have previously demonstrated that a dietary low ω6/ω3 polyunsaturated fatty acid (PUFA) ratio protects against ELS-induced cognitive impairments. Several studies have implicated the neuroimmune system in the ELS and diet mediated effects, but currently the molecular pathways via which ELS and early diet exert their long-term impact are not yet fully understood. Here we study the effects of ELS and dietary PUFA ratio on hippocampal mRNA and miRNA expression in adulthood, both under basal and inflammatory conditions.Male mice were exposed to chronic ELS by the limiting bedding and nesting material paradigm from postnatal day(P)2 to P9, and provided with a diet containing a high (15:1.1) or low (1.1:1) ω6 linoleic acid to ω3 alpha-linolenic acid ratio from P2 to P42. At P120, memory was assessed using the object location task. Subsequently, a single lipopolysaccha...
Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depre... more Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (postnatal days [P]2–9) on microglial i) morphology; ii) hippocampal gene expression; and iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, s...
Neuroscience & Biobehavioral Reviews, 2022
Early-life adversity (ELA) is a major risk factor for developing later-life mental and metabolic ... more Early-life adversity (ELA) is a major risk factor for developing later-life mental and metabolic disorders. However, if and to what extent ELA contributes to the comorbidity and sex-dependent prevalence/presentation of these disorders remains unclear. We here comprehensively review and integrate human and rodent ELA (pre- and postnatal) studies examining mental or metabolic health in both sexes and discuss the role of the placenta and maternal milk, key in transferring maternal effects to the offspring. We conclude that ELA impacts mental and metabolic health with sex-specific presentations that depend on timing of exposure, and that human and rodent studies largely converge in their findings. ELA is more often reported to impact cognitive and externalizing domains in males, internalizing behaviors in both sexes and concerning the metabolic dimension, adiposity in females and insulin sensitivity in males. Thus, ELA seems to be involved in the origin of the comorbidity and sex-specific prevalence/presentation of some of the most common disorders in our society. Therefore, ELA-induced disease states deserve specific preventive and intervention strategies.
CNS Drugs, 2017
Over the past few decades, research on Alzheimer's disease (AD) has focused on pathomechanisms li... more Over the past few decades, research on Alzheimer's disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intraneuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as dangerassociated molecular patterns, that-upon engagement of pattern recognition receptors-induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on
Frontiers in Human Neuroscience, 2016
Glia are essential for brain functioning during development and in the adult brain. Here, we disc... more Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis and synaptic pruning. Due to their important instructive roles in these processes, dysfunction of microglia or astrocytes during brain development could contribute to neurodevelopmental disorders and potentially even late-onset neuropathology. A better understanding of the origin, differentiation process and developmental functions of microglia and astrocytes will help to fully appreciate their role both in the developing as well as in the adult brain, in health and disease.
Investigative Ophthalmology & Visual Science, 2015
Early-life stress (ELS) leads to increased vulnerability for mental and metabolic disorders. We h... more Early-life stress (ELS) leads to increased vulnerability for mental and metabolic disorders. We have previously shown that dietary low ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratio is able to protect against ELS-induced cognitive impairments. Due to the importance of the gut microbiota as determinants of long-term health, we here study the impact of ELS and dietary PUFA’s on the gut microbiota, and how this relates to the previously described cognitive, metabolic and fatty acid profiles.Male mice were exposed to ELS via the limited bedding and nesting paradigm (postnatal day (P)2 – P9) and to an early diet (P2 – P42) with either high (15) or low (1) ω-6 linoleic acid to ω-3 alpha-linolenic acid ratio. 16S ribosomal RNA was sequenced and analyzed from fecal samples at P21, P42 and P180.ELS increased β-diversity at P42, which persisted into adulthood. The low ω-6/ω-3 diet prevented the ELS-induced increase in β-diversity, at P42. At the level of taxa abundance, for example, the abun...
Early-life stress (ELS) exposure increases the risk for mental disorders, including cognitive imp... more Early-life stress (ELS) exposure increases the risk for mental disorders, including cognitive impairments later in life. We have previously demonstrated that a dietary low ω6/ω3 polyunsaturated fatty acid (PUFA) ratio protects against ELS-induced cognitive impairments. Several studies have implicated the neuroimmune system in the ELS and diet mediated effects, but currently the molecular pathways via which ELS and early diet exert their long-term impact are not yet fully understood. Here we study the effects of ELS and dietary PUFA ratio on hippocampal mRNA and miRNA expression in adulthood, both under basal and inflammatory conditions.Male mice were exposed to chronic ELS by the limiting bedding and nesting material paradigm from postnatal day(P)2 to P9, and provided with a diet containing a high (15:1.1) or low (1.1:1) ω6 linoleic acid to ω3 alpha-linolenic acid ratio from P2 to P42. At P120, memory was assessed using the object location task. Subsequently, a single lipopolysaccha...
Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depre... more Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (postnatal days [P]2–9) on microglial i) morphology; ii) hippocampal gene expression; and iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, s...
Neuroscience & Biobehavioral Reviews, 2022
Early-life adversity (ELA) is a major risk factor for developing later-life mental and metabolic ... more Early-life adversity (ELA) is a major risk factor for developing later-life mental and metabolic disorders. However, if and to what extent ELA contributes to the comorbidity and sex-dependent prevalence/presentation of these disorders remains unclear. We here comprehensively review and integrate human and rodent ELA (pre- and postnatal) studies examining mental or metabolic health in both sexes and discuss the role of the placenta and maternal milk, key in transferring maternal effects to the offspring. We conclude that ELA impacts mental and metabolic health with sex-specific presentations that depend on timing of exposure, and that human and rodent studies largely converge in their findings. ELA is more often reported to impact cognitive and externalizing domains in males, internalizing behaviors in both sexes and concerning the metabolic dimension, adiposity in females and insulin sensitivity in males. Thus, ELA seems to be involved in the origin of the comorbidity and sex-specific prevalence/presentation of some of the most common disorders in our society. Therefore, ELA-induced disease states deserve specific preventive and intervention strategies.
CNS Drugs, 2017
Over the past few decades, research on Alzheimer's disease (AD) has focused on pathomechanisms li... more Over the past few decades, research on Alzheimer's disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intraneuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as dangerassociated molecular patterns, that-upon engagement of pattern recognition receptors-induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on
Frontiers in Human Neuroscience, 2016
Glia are essential for brain functioning during development and in the adult brain. Here, we disc... more Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis and synaptic pruning. Due to their important instructive roles in these processes, dysfunction of microglia or astrocytes during brain development could contribute to neurodevelopmental disorders and potentially even late-onset neuropathology. A better understanding of the origin, differentiation process and developmental functions of microglia and astrocytes will help to fully appreciate their role both in the developing as well as in the adult brain, in health and disease.
Investigative Ophthalmology & Visual Science, 2015
Early-life stress (ELS) leads to increased vulnerability for mental and metabolic disorders. We h... more Early-life stress (ELS) leads to increased vulnerability for mental and metabolic disorders. We have previously shown that dietary low ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratio is able to protect against ELS-induced cognitive impairments. Due to the importance of the gut microbiota as determinants of long-term health, we here study the impact of ELS and dietary PUFA’s on the gut microbiota, and how this relates to the previously described cognitive, metabolic and fatty acid profiles.Male mice were exposed to ELS via the limited bedding and nesting paradigm (postnatal day (P)2 – P9) and to an early diet (P2 – P42) with either high (15) or low (1) ω-6 linoleic acid to ω-3 alpha-linolenic acid ratio. 16S ribosomal RNA was sequenced and analyzed from fecal samples at P21, P42 and P180.ELS increased β-diversity at P42, which persisted into adulthood. The low ω-6/ω-3 diet prevented the ELS-induced increase in β-diversity, at P42. At the level of taxa abundance, for example, the abun...