Landscape of brain myeloid cell transcriptome along the spatiotemporal progression of Alzheimer's disease reveals distinct sequential responses to Aβ and tau.

Human microglia are critically involved in Alzheimer's disease (AD) progression, as shown by genetic and molecular studies. However, their role in tau pathology progression in human brain has not been well described. Here, we characterized 32 human donors along progression of AD pathology, both in time-from early to late pathology-and in space-from entorhinal cortex (EC), inferior temporal gyrus (ITG), prefrontal cortex (PFC) to visual cortex (V2 and V1)-with biochemistry, immunohistochemistry, and single nuclei-RNA-sequencing, profiling a total of 337,512 brain myeloid cells, including microglia.

Distinct transcriptomic responses to Aβ plaques, neurofibrillary tangles, and APOE in Alzheimer's disease.

Introduction: Omics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimer's disease (AD) but the spatial relationships with plaques and tangles and APOE-linked differences remain unclear.

Methods: We performed laser capture microdissection of amyloid beta (Aβ) plaques, the 50 μm halo around them, tangles with the 50 μm halo around them, and areas distant (> 50 μm) from plaques and tangles in the temporal cortex of AD and control donors, followed by RNA-sequencing.

Results: Aβ plaques exhibited upregulated microglial (neuroinflammation/phagocytosis) and downregulated neuronal (neurotransmission/energy metabolism) genes, whereas tangles had mostly downregulated neuronal genes.

Distinct Transcriptomic Responses to Aβ plaques, Neurofibrillary Tangles, and in Alzheimer's Disease.

Introduction: Omics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimer's disease (AD) but the spatial relationships with plaques and tangles and -linked differences remain unclear.

Methods: We performed laser capture microdissection of Aβ plaques, the 50μm halo around them, tangles with the 50μm halo around them, and areas distant (>50μm) from plaques and tangles in the temporal cortex of AD and control donors, followed by RNA-sequencing.

Results: Aβ plaques exhibited upregulated microglial (neuroinflammation/phagocytosis) and downregulated neuronal (neurotransmission/energy metabolism) genes, whereas tangles had mostly downregulated neuronal genes.

Immune hyperreactivity of Aβ plaque-associated microglia in Alzheimer's disease.

Alzheimer's disease (AD) is strongly associated with microglia-induced neuroinflammation. Particularly, Aβ plaque-associated microglia take on an "activated" morphology. However, the function and phenotype of these Aβ plaque-associated microglia are not well understood.

Chronic vortioxetine treatment in rodents modulates gene expression of neurodevelopmental and plasticity markers.

The multimodal antidepressant vortioxetine displays an antidepressant profile distinct from those of conventional selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and possesses cognitive-enhancing properties in preclinical and clinical studies. Recent studies have begun to investigate molecular mechanisms that may differentiate vortioxetine from other antidepressants. Acute studies in adult rats and chronic studies in a middle-aged mouse model reveal upregulation of several markers that play a central role in synaptic plasticity.

In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity.

Neuroplasticity is fundamental for brain functions, abnormal changes of which are associated with mood disorders and cognitive impairment. Neuroplasticity can be affected by neuroactive medications and by aging. Vortioxetine, a multimodal antidepressant, has shown positive effects on cognitive functions in both pre-clinical and clinical studies.

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice.

Cognitive decline occurs during healthy aging, even in middle-aged subjects, via mechanisms that could include reduced stem cell proliferation, changed growth factor expression and/or reduced expression of synaptic plasticity genes. Although antidepressants alter these mechanisms in young rodents, their effects in older animals are unclear. In middle-aged mice, we examined the effects of a selective serotonin reuptake inhibitor (fluoxetine) and a multimodal antidepressant (vortioxetine) on cognitive and affective behaviors, brain stem cell proliferation, growth factor and gene expression.

Gene expression profiles in relation to tension and dissociation in borderline personality disorder.

The biological underpinnings of borderline personality disorder (BPD) and its psychopathology including states of aversive tension and dissociation is poorly understood. Our goal was to examine transcriptional changes associated with states of tension or dissociation within individual patients in a pilot study. Dissociation is not only a critical symptom of BPD but has also been associated with higher risk for self-mutilation and depression.

Chromium supplementation improves glucose tolerance in diabetic Goto-Kakizaki rats.

Chromium supplementation (Cr) may be useful in the management of diabetes and appears to improve some aspects of glucose handling. However, several studies have used either high doses of Cr supplementation or have placed control animals on a Cr-deficient diet. We therefore wanted to test whether Cr dosages in the ranges that more closely approximate recommended levels of supplementation in humans are efficacious in glycemic control under normal dietary conditions.

Early adaptations to training: upregulation of alpha-myosin heavy chain gene expression.

Unlabelled: Chronic exercise induces adaptations that increase the functional capacity of the cardiovascular system. Aside from ventricular growth, these adaptations include a shift in the MHC isoenzyme pattern to enhance ventricular contractility. It is unclear whether adaptations by the contractile elements are an early event and specific to exercise, or whether they progress as a function of cardiac growth.