Neuroscience
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Alzheimer's disease (AD) is associated with hippocampal neuropathology and cognitive impairments, including wandering behavior or becoming lost in a familiar environment. Wandering behavior is severe and manifests early in life for people with specific genetic mutations. Genetic mouse models of AD have been developed to characterize the onset and progression of behavioral deficits that represent human behaviors, such as wandering, to test the efficacy of therapeutics. ⋯ Spatial disorientation was observed at two months and more severely at four months under dark conditions, but performance was spared when visual environmental cues were available. This study provides documentation of impaired self-movement cue processing in AD mice, establishing the dark open field as a behavioral tool to characterize spatial disorientation associated with AD. These findings may accelerate future assessments of novel therapeutic interventions for neurological disorders.
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Parkinson's disease (PD) is the world's second primary neurodegenerative disease, and the diagnosis and treatment of PD have become mainstream research. Over the past decades, several studies have identified potential biomarkers for diagnosing PD. Among them, extracellular vesicles (EVs) can carry specific biomarkers reflecting the physiological and pathological state of the body. ⋯ In this review, we summarized previous studies on PD diagnosis biomarkers in peripheral blood EVs and evaluated their diagnostic value. Some EV surface markers were also described, which can extract EVs from specific cell origins. In addition, the combination of several biomarkers demonstrated good diagnostic performance in PD diagnosis compared with a single biomarker, suggesting the focus of future research.
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Nuclear TAR DNA-binding protein 43 (TDP-43) mitigates cellular function, but the dynamic nucleus-cytoplasm shuttling of TDP-43 is disrupted in diseases, such as Amyotrophic Lateral Sclerosis (ALS). The polymorphic nature of the TDP-43 structures in vitro and in vivo is a result of environmental factors leading to the protein pathogenesis. Once the triggers which mitigate TDP-43 biochemistry are identified, new therapies can be developed. This review aims to illustrate recent discoveries in the diversity of TDP-43 structures (amyloidogenic and non-amyloidogenic) and highlight the triggers which result in their formation.
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Review
Relevance of biochemical deep phenotyping for a personalised approach to Parkinson's disease.
Parkinson's disease (PD) is a multifactorial neurodegenerative disorder characterised by the progressive loss of dopaminergic neurons in the nigrostriatal tract. The identification of disease-modifying therapies is the Holy Grail of PD research, but to date no drug has been approved as such a therapy. A possible reason is the remarkable phenotypic heterogeneity of PD patients, which can generate confusion in the interpretation of results or even mask the efficacy of a therapeutic intervention. ⋯ The analyte most studied is α-synuclein, while other studies have focused on neurofilament light chain, lysosomal proteins, inflammasome-related proteins, LRRK2 and the urinary proteome. At present, stratification of PD patients, while promising, is still a nascent approach. Deep phenotyping of patients will allow clinical researchers to identify homogeneous subgroups for the investigation of tailored disease-modifying therapies, enhancing the chances of therapeutic success.
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Pregnancy is associated with profound acute and long-term physiological changes, but the effects of such changes on brain injury outcomes are unclear. Here, we examined the effects of previous pregnancy and maternal experience (parity) on acute neuroinflammatory responses to lateral fluid percussion injury (FPI), a well-defined experimental traumatic brain injury (TBI) paradigm. Multiparous (2-3 pregnancies and motherhood experiences) and age-matched nulliparous (no previous pregnancy or motherhood experience) female mice received either FPI or sham injury and were euthanized 3 days post-injury (DPI). ⋯ However, multiparous females had fewer CD45+ cells near the site of injury compared to nulliparous females, which was associated with preserved aquaporin-4 polarization, suggesting that parity may influence leukocyte recruitment to the site of injury and maintenance of blood brain barrier permeability following TBI. Additionally, relative cortical Il6 gene expression following TBI was dependent on parity such that TBI increased Il6 expression in nulliparous, but not multiparous, mice. Together, this work suggests that reproductive history may influence acute neuroinflammatory outcomes following TBI in females.