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Biology subjects

Dickens, S.

Publications and source records attributed to Dickens, S..

3 recordsLinked to original sources

NREM sleep microarchitecture is associated with internalizing symptoms and emotional functioning in early adolescence

Study Objectives: Sleep disturbances are common in youth with anxiety disorders, yet most prior work relies on subjective measures and does not capture underlying neural processes. We examined whether alterations in non-rapid eye movement (NREM) sleep oscillations are present in children with anxiety disorders and whether these features relate to internalizing symptoms and emotional functioning. Methods: Children aged 9-13 years with diagnosed anxiety disorders (ANX; n = 17) and typically developing non-psychiatric comparison participants (NC; n = 26) completed overnight polysomnography. Slow oscillations (SO) and slow and fast sleep spindles were characterized using validated automated detection algorithms. Participants also completed a pre-sleep emotional processing task, and parents provided standardized measures of youth mental health. Group differences and dimensional associations between NREM oscillations, internalizing symptoms, and behavioral indices of emotional processing were examined. Results: Sleep architecture did not differ between groups. Slow spindle duration was shorter in the ANX group. Across the full sample, shorter slow spindle duration was associated with greater internalizing symptoms, whereas higher SO density was positively associated with internalizing symptoms. Children in the ANX group exhibited greater facial emotional arousal and more frequent look-away behavior during the emotional processing task. Across participants, greater emotional arousal and look-away behavior were associated with shorter spindle duration during subsequent sleep. Conclusions: Specific features of NREM microarchitecture were associated with individual differences in internalizing symptoms and emotional functioning during early adolescence. These findings highlight the potential relevance of NREM oscillations for understanding developmental links between sleep and youth psychopathology.

neuroscience↗

A stem cell secretome delays functional decline and supresses inflammation in two distinct models of neurodegeneration.

Alzheimers disease (AD) is a progressive neurodegenerative disorder with a rapidly increasing global prevalence. Current pharmacological interventions offer symptomatic relief but do not modify disease progression. Secretome-based therapeutics have emerged as a potential disease-modifying strategy, given their capacity to influence multiple pathological pathways, including amyloid burden, reactive gliosis, and neuronal survival. Early clinical studies support the safety and potential efficacy of these approaches, indicating mechanisms involving neuroprotection, neurodegeneration, and modulation of neuroinflammation, processes central to AD pathology. In the present study, we investigated the therapeutic efficacy of multipotent stromal cell (MSC)-derived secretomes produced by a specific platform (Secretomix) in two distinct mouse models of neurodegenerative disease: An AD model characterized by amyloid pathology, and a motor neurone disease (MND) model exhibiting TDP-43 protein aggregation. Administration of the MSC secretome resulted in a positive modulation of the behavioural phenotype in the AD model, and reduction in the rate of decline of motor co-ordination (attenuated the progression of motor deficits) in the MND model. In the latter, these functional benefits were accompanied by a measurable reduction in neuroinflammatory responses but without direct alteration of standard neuropathological markers. Additionally, ex vivo assays using human peripheral blood demonstrated broad anti-inflammatory activity of the MSC secretome, providing a potential mechanistic basis for the in vivo observations. Collectively, these findings support further investigation of MSC-derived secretomes as a promising therapeutic approach for neurodegenerative disorders, with relevance across proteinopathies characterised by distinct molecular pathways. Significance StatementHere we demonstrate the efficacy of a stem cell secretome in ameliorating cognitive and behavioural phenotypes in different models of neurodegeneration. These models represent distinct neuropathological features that are unaffected by stem cell secretome treatment but share common features of modulation of inflammation post stem cell secretome treatment. This study highlights the therapeutic potential of stem cell secretomes in the treatment of neurodegenerative conditions with an already existing neuropathology.

neuroscience↗

An in vitro neuronal model replicating the in vivo maturation and heterogeneity of perineuronal nets

The perineuronal net (PNN) is a condensed form of extracellular matrix (ECM) that enwraps specific populations of neurons and regulates plasticity. To create a PNN, only three classes of components are needed: membrane bound hyaluronan by its synthetic enzyme hyaluronan synthases (HASs), a link protein and a CSPG. However, there is redundancy within the classes as multiple HAS isoforms, link proteins and CSPGs have been found in the PNN in vivo. The effect of this heterogeneity has on PNN function is unresolved. Currently, the most common way to address this question is through the creation and study of PNN component in knockout animals. Here, we reported the development of a primary neuronal culture model which reproduces the in vivo maturation and heterogeneity of PNNs. This model accurately replicated mature cortical PNNs, both in terms of the heterogeneity in PNN composition and its maturation. PNNs transitioned from an immature punctate morphology to the reticular morphology as observed in the mature CNS. We also observed a small population of PNNs that were mature at an earlier time point and a distinct composition, highlighting further heterogeneity. This model will provide a valuable tool for the study of PNN biology, their roles in diseases and the development of PNN focused plasticity treatment.

neuroscience↗