Down syndrome

Down syndrome (DS) results from chromosome 21 trisomy, causing cognitive and developmental challenges often accompanied by hearing deficits. Studies on humans using EEG and MEG have identified prolonged latencies in sound-evoked responses in DS. However, the origin and characteristics of these deficits remain unclear. This study investigates auditory processing in a DS rat model to determine whether sensory deficits arise from early processing areas, such as the auditory thalamus and primary auditory cortex (A1), or higher-level cognitive alterations. We conducted neural activity recordings, u

…21, is present in extra copy in Down syndrome (DS). Dysregulation of H2S signalling has been linked to DS, but the precise underlying mechanisms are yet to be fully identified. Therefore, this study aims to establish and characterize induced pluripotent stem cell (iPSC) lines reprogrammed from peripheral blood mononuclear cells (PBMC) collected from a blood sample of a paediatric DS patient (T21) and an age-matched apparently healthy donor (Eup), and also to derive iPSC into neura

…of the Ts65Dn mouse model of Down syndrome. This depends on the upregulation of the Cl-importer NKCC1 and leads to an impairment of synaptic plasticity and memory in Ts65Dn adult mice. Accordingly, inhibiting NKCC1 rescues the Ts65Dn phenotype. However, the contribution of specific interneuron subpopulations t

Down syndrome (DS) patients who show mental retardation also present acquired anosmia, i.e., the loss of odor detection. At the present time, no viable treatment exists for cognitive and olfactory deficits in DS. Interestingly, the ability to reach puberty and become fertile is also affected in these patients. An intriguing candidate, whose absence could mediate most of these phenotypes, is the gonadotropin-releasing hormone (GnRH), the neurohormone controlling reproduction. However, whether GnRH plays a role in the age-related cognitive decline in DS is unknown.We showed in Ts65dn mice, a wel

In mouse models of Down syndrome (DS), cognitive deficits such as memory impairment are believed to be caused by overinhibition. However, recent studies indicate that the overexpression of Grik1, a gene mainly expressed at interneurons in the hippocampus, could be a key driver of memory deficits in individuals with DS due to a bidirectional alteration of synaptic inhibition on CA1 pyramidal cells (Valbuena et al, Nature Comms. 2019, 10:4991). Remarkably, normalizing Grik1 dosage in the Ts2Cje mouse model of DS specifically restores spatial memory and reverses the bidirectional alterations to C

Down syndrome (Trisomy 21, Ts21) is the most common cause of early onset Alzheimer’s disease. We previously reported that secretomes of induced pluripotent stem cell (iPSC)-derived human Ts21 cortical neurons inhibited hippocampal long-term potentiation (LTP) in a tau-dependent manner (Hu et al., Cell Reports, 2018). Here, we employed electrophysiological recording from the CA1 area of the hippocampus of live rats under urethane anaesthesia to assess the ability of anti-tau antibodies to immunodeplete Ts21 iPSC-derived neuron synaptotoxic tau. We found that the mid-region (amino acids 210-241)

Down syndrome (DS) is characterized by deficits in neuronal activity and connectivity, with unclear contributions from different cell types. Microglia, the brain's immune cells, shape neuronal circuits by influencing the number of synaptic connections, both excitatory and inhibitory. This study investigates the microglial involvement in DS-related connectivity deficits. Using in vivo mesoscale wide-field calcium imaging, we analyzed the cortical connectivity of Ts65Dn and euploid mice injected retroorbitally with a CAMKII-GCaMP7f viral vector, in response to a drug effective in blocking neuron

Neurogenesis requires the coordinated interplay between different cell types within the specialized microenvironment of the neurogenic niche. An important role is played by glia which, among their homeostatic roles, also include modulation of neural stem cells and their progeny.We will share and discuss recent molecular, biochemical and pharmacological data supporting an important role of astroglial cells in the modulation of neurogenesis under both physiological and pathological conditions, including aging and neurodegeneration. Particularly, focus will be on the role of astrocytes and their

Research has shown that individuals with Down syndrome experience altered pain sensitivity, with varying results depending on the type of nociceptive stimulus. GRIK1, a gene coding for the GluK1 subunit of kainate receptors is triplicated in Down syndrome. This subunit is heavily expressed in Dorsal Root Ganglion neurons and has been implicated in modulating pain perception. To investigate this further, we have conducted experiments in the Ts2Cje mouse model of Down syndrome, comparing them to mice lacking Grik1. The results suggest that altered pain perception in Down syndrome is dependent on

Down syndrome (DS) individuals are characterized by a variety of pathological phenotypes that manifest with wide variability in different tissues. In the central nervous system, the accelerated aging phenotype is associated with the risk of developing Alzheimer-like dementia. A central aspect of neurodegeneration is the close association between metabolic disorders and cognitive decline. Multiple studies have suggested a link between metabolic disorder and microRNAs (miR), small non-coding RNAs acting as post-transcriptional regulators of a plethora of genes. Among triplicated miRNAs on chromo

…autism spectrum disorders (ASD), Down syndrome (DS), and drug-resistant epilepsy (DRE). Interestingly, NKCC1 inhibition rescues core symptoms of these brain conditions in rodent models and/or clinical trials. However, current NKCC1 inhibitors have diuretic effects by also inhibiting the kidney Cl transporter NKCC2. These diuretic effects pose critical health conc

Down syndrome is a common neurodevelopmental condition and major genetic cause of intellectual disability. Although trisomy of chromosome 21 is long known as underlying cause, it is not well understood how the increased dosage of over 300 genes on chromosome 21 perturbs transcriptional and epigenetic programmes underlying neural differentiation, and effective therapies are lacking. Mouse models have suggested potential underlying mechanisms, but it is unclear to what extent these are recapitulated in the human brain.Here, we use single cell transcriptomics and epigenomics to generate an atlas

…a particular focus on a subgroup of Down Syndrome (DS) patients afflicted by AD (AD in DS). Our objective is to explore the overlaps and distinctions between sporadic AD (sAD) and AD in DS, thereby providing insights that may bridge the gap between animal models and human AD conditions. We employed spatial transcriptomics (ST) in conjunction with

…"The Alana Down Syndrome Center (ADSC) aims to deepen knowledge about Down syndrome and to improve health, autonomy and inclusion of people with this genetic condition." "The ABI and the ADSC have joined forces for this year's symposium to highlight how aging-related changes to the brain overlap with neurological aspects of Down syndrome. Our hope is to encourage greater collaboration between the brai

…"The Alana Down Syndrome Center (ADSC) aims to deepen knowledge about Down syndrome and to improve health, autonomy and inclusion of people with this genetic condition." "The ABI and the ADSC have joined forces for this year's symposium to highlight how aging-related changes to the brain overlap with neurological aspects of Down syndrome. Our hope is to encourage greater collaboration between the brai

Neurodevelopmental disorders are a group of very heterogeneous diseases in which the development of the central nervous system is defective. In neurodevelopmental disorders defective brain development translates into aberrant brain function, which can manifest for example as impaired learning, motor function, or social interaction. Despites years of investigation in animal models and clinical research on neurodevelopmental disorders, there are currently no approved pharmacological treatments for core symptoms of the vast majority of them. Here, I will share some recent work (but also some appr