The global and regional burden of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is length-dependent peripheral nerve damage arising as a complication of type 1 or type 2 diabetes in up to 50% of patients. DPN poses a substantial burden on patients, who can experience impaired gait and loss of balance, predisposing them to falls and fractures, and neuropathic pain, which is frequently difficult to treat and reduces quality of life. Advanced DPN can lead to diabetic foot ulcers and non-healing wounds that often necessitate lower-limb amputation.

Human neural stem cells restore spatial memory in a transgenic Alzheimer's disease mouse model by an immunomodulating mechanism.

Introduction: Stem cells are a promising therapeutic in Alzheimer's disease (AD) given the complex pathophysiologic pathways involved. However, the therapeutic mechanisms of stem cells remain unclear. Here, we used spatial transcriptomics to elucidate therapeutic mechanisms of human neural stem cells (hNSCs) in an animal model of AD.

Non-invasive in vivo measurements of metabolic alterations in the type 2 diabetic brain by H magnetic resonance spectroscopy.

Type 2 diabetes (T2D) is a complex chronic metabolic disorder characterized by hyperglycemia because of insulin resistance. Diabetes with chronic hyperglycemia may alter brain metabolism, including brain glucose and neurotransmitter levels; however, detailed, longitudinal studies of metabolic alterations in T2D are lacking. To shed insight, here, we characterized the consequences of poorly controlled hyperglycemia on neurochemical profiles that reflect metabolic alterations of the brain in both humans and animal models of T2D.

Regional interneuron transcriptional changes reveal pathologic markers of disease progression in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and leading cause of dementia, characterized by neuronal and synapse loss, amyloid-β and tau protein aggregates, and a multifactorial pathology involving neuroinflammation, vascular dysfunction, and disrupted metabolism. Additionally, there is growing evidence of imbalance between neuronal excitation and inhibition in the AD brain secondary to dysfunction of parvalbumin (PV)- and somatostatin (SST)-positive interneurons, which differentially modulate neuronal activity. Importantly, impaired interneuron activity in AD may occur upstream of amyloid-β pathology rendering it a potential therapeutic target.

Palmitate and glucose increase amyloid precursor protein in extracellular vesicles: Missing link between metabolic syndrome and Alzheimer's disease.

The metabolic syndrome (MetS) and Alzheimer's disease share several pathological features, including insulin resistance, abnormal protein processing, mitochondrial dysfunction and elevated inflammation and oxidative stress. The MetS constitutes elevated fasting glucose, obesity, dyslipidaemia and hypertension and increases the risk of developing Alzheimer's disease, but the precise mechanism remains elusive. Insulin resistance, which develops from a diet rich in sugars and saturated fatty acids, such as palmitate, is shared by the MetS and Alzheimer's disease.

Gut microbiome correlates with plasma lipids in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a complex, fatal neurodegenerative disease. Disease pathophysiology is incompletely understood but evidence suggests gut dysbiosis occurs in ALS, linked to impaired gastrointestinal integrity, immune system dysregulation and altered metabolism. Gut microbiome and plasma metabolome have been separately investigated in ALS, but little is known about gut microbe-plasma metabolite correlations, which could identify robust disease biomarkers and potentially shed mechanistic insight.

The amyotrophic lateral sclerosis exposome: recent advances and future directions.

Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration with typical survival of only 2-5 years from diagnosis. The causes of ALS are multifactorial: known genetic mutations account for only around 70% of cases of familial ALS and 15% of sporadic cases, and heritability estimates range from 8% to 61%, indicating additional causes beyond genetics. Consequently, interest has grown in environmental contributions to ALS risk and progression.

Engineered extracellular matrices facilitate brain organoids from human pluripotent stem cells.

Objective: Brain organoids are miniaturized in vitro brain models generated from pluripotent stem cells, which resemble full-sized brain more closely than conventional two-dimensional cell cultures. Although brain organoids mimic the human brain's cell-to-cell network interactions, they generally fail to faithfully recapitulate cell-to-matrix interactions. Here, an engineered framework, called an engineered extracellular matrix (EECM), was developed to provide support and cell-to-matrix interactions to developing brain organoids.

New perspectives in diabetic neuropathy.

Diabetes prevalence continues to climb with the aging population. Type 2 diabetes (T2D), which constitutes most cases, is metabolically acquired. Diabetic peripheral neuropathy (DPN), the most common microvascular complication, is length-dependent damage to peripheral nerves.

Gut microbiota in a mouse model of obesity and peripheral neuropathy associated with plasma and nerve lipidomics and nerve transcriptomics.

Background: Peripheral neuropathy (PN) is a common complication in obesity, prediabetes, and type 2 diabetes, though its pathogenesis remains incompletely understood. In a murine high-fat diet (HFD) obesity model of PN, dietary reversal (HFD-R) to a low-fat standard diet (SD) restores nerve function and the nerve lipidome to normal. As the gut microbiome represents a potential link between dietary fat intake and nerve health, the current study assessed shifts in microbiome community structure by 16S rRNA profiling during the paradigm of dietary reversal (HFD-R) in various gut niches.

Single-cell RNA sequencing identifies hippocampal microglial dysregulation in diet-induced obesity.

Obesity is a growing global concern in adults and youth with a parallel rise in associated complications, including cognitive impairment. Obesity induces brain inflammation and activates microglia, which contribute to cognitive impairment by aberrantly phagocytosing synaptic spines. Local and systemic signals, such as inflammatory cytokines and metabolites likely participate in obesity-induced microglial activation.

Body mass index associates with amyotrophic lateral sclerosis survival and metabolomic profiles.

Introduction/aims: Body mass index (BMI) is linked to amyotrophic lateral sclerosis (ALS) risk and prognosis, but additional research is needed. The aim of this study was to identify whether and when historical changes in BMI occurred in ALS participants, how these longer term trajectories associated with survival, and whether metabolomic profiles provided insight into potential mechanisms.

Methods: ALS and control participants self-reported body height and weight 10 (reference) and 5 years earlier, and at study entry (diagnosis for ALS participants).

Diabetes and dementia: Clinical perspective, innovation, knowledge gaps.

The world faces a pandemic-level prevalence of type 2 diabetes. In parallel with this massive burden of metabolic disease is the growing prevalence of dementia as the population ages. The two health issues are intertwined.

miRNA analysis reveals novel dysregulated pathways in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Its complex pathogenesis and phenotypic heterogeneity hinder therapeutic development and early diagnosis. Altered RNA metabolism is a recurrent pathophysiologic theme, including distinct microRNA (miRNA) profiles in ALS tissues.

Amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a fatal CNS neurodegenerative disease. Despite intensive research, current management of amyotrophic lateral sclerosis remains suboptimal from diagnosis to prognosis. Recognition of the phenotypic heterogeneity of amyotrophic lateral sclerosis, global CNS dysfunction, genetic architecture, and development of novel diagnostic criteria is clarifying the spectrum of clinical presentation and facilitating diagnosis.

Towards prevention of diabetic peripheral neuropathy: clinical presentation, pathogenesis, and new treatments.

Diabetic peripheral neuropathy (DPN) occurs in up to half of individuals with type 1 or type 2 diabetes. DPN results from the distal-to-proximal loss of peripheral nerve function, leading to physical disability and sometimes pain, with the consequent lowering of quality of life. Early diagnosis improves clinical outcomes, but many patients still develop neuropathy.

Serum lipidomic determinants of human diabetic neuropathy in type 2 diabetes.

Objective: The serum lipidomic profile associated with neuropathy in type 2 diabetes is not well understood. Obesity and dyslipidemia are known neuropathy risk factors, suggesting lipid profiles early during type 2 diabetes may identify individuals who develop neuropathy later in the disease course. This retrospective cohort study examined lipidomic profiles 10 years prior to type 2 diabetic neuropathy assessment.

Migrating Pyramidal Neurons Require DSCAM to Bypass the Border of the Developing Cortical Plate.

During mammalian neocortex development, nascent pyramidal neurons migrate along radial glial cells and overtake earlier-born neurons to terminate at the front of the developing cortical plate (CP), leading to the outward expansion of the CP border. While much has been learned about the cellular and molecular mechanisms that underlie the migration of pyramidal neurons, how migrating neurons bypass the preceding neurons at the end of migration to reach their final positions remains poorly understood. Here, we report that Down syndrome cell adhesion molecule (DSCAM) is required for migrating neurons to bypass their postmigratory predecessors during the expansion of the upper cortical layers.

Glial-neuron crosstalk in health and disease: A focus on metabolism, obesity, and cognitive impairment.

Dementia is a complex set of disorders affecting normal cognitive function. Recently, several clinical studies have shown that diabetes, obesity, and components of the metabolic syndrome (MetS) are associated with cognitive impairment, including dementias such as Alzheimer's disease. Maintaining normal cognitive function is an intricate process involving coordination of neuron function with multiple brain glia.

Systems Biology to Address Unmet Medical Needs in Neurological Disorders.

Neurological diseases are highly prevalent and constitute a significant cause of mortality and disability. Neurological disorders encompass a heterogeneous group of neurodegenerative conditions, broadly characterized by injury to the peripheral and/or central nervous system. Although the etiology of neurological diseases varies greatly, they share several characteristics, such as heterogeneity of clinical presentation, non-cell autonomous nature, and diversity of cellular, subcellular, and molecular pathways.

Neurological sequela and disruption of neuron-glia homeostasis in SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic is responsible for 267 million infections and over 5 million deaths globally. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded RNA beta-coronavirus, which causes a systemic inflammatory response, multi-organ damage, and respiratory failure requiring intubation in serious cases. SARS-CoV-2 can also trigger neurological conditions and syndromes, which can be long-lasting and potentially irreversible.