Alpha-lipoic acid supplementation improves pathological alterations in cellular models of Friedreich ataxia.

Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia, is characterized by degeneration of the large sensory neurons and spinocerebellar tracts, cardiomyopathy, and an increased incidence of diabetes. The underlying pathophysiological mechanism of FRDA, driven by a significantly decreased expression of frataxin (FXN), involves increased oxidative stress, reduced activity of enzymes containing iron‑sulfur clusters, defective energy production, calcium dyshomeostasis, and impaired mitochondrial biogenesis, leading to mitochondrial dysfunction.

Methods: This study is aimed at evaluating the role of alpha-lipoic acid (ALA) in reversing the pathological alterations in fibroblasts and induced neurons derived from FRDA patients.

Transformation of radial glia into postnatal neural stem cells depends on birth.

A common feature of various postnatal stem cells is their close association with blood vessels. Postnatal neural stem cells (NSCs) in the ventricular-subventricular zone originate from fetal radial glia (RG), which possess NSC properties. Here, using live imaging and three-dimensional (3D) electron microscopy, we investigated how RG convert into postnatal NSCs and characterized the fine 3D morphology of the ventricular-subventricular zone.

Neuronal migration depends on blood flow in the adult brain.

In animal tissues, several cell types migrate along blood vessels, raising the possibility that blood flow influences cell migration. Here, we show that blood flow promotes the migration of new olfactory-bulb neurons in the adult brain. Neuronal migration is facilitated by blood flow, leading to accumulation of new neurons near blood vessels with abundant blood flow.

Remyelination of chronic demyelinated lesions with directly induced neural stem cells.

The limited ability of CNS progenitor cells to differentiate into oligodendrocytes limits the repair of demyelinating lesions and contributes to the disability of people with progressive multiple sclerosis (PMS). Neural stem cell (NSC) transplantation has emerged as a safe therapeutic approach in people with PMS, where it holds the promise of healing the injured CNS. However, the mechanisms by which NSC grafts could promote CNS remyelination need to be carefully assessed before their widespread clinical adoption.

Cellular Organization and Migration Pathways of the Ventricular-Subventricular Zone in the Juvenile Swine Brain (Sus scrofa domesticus).

The ventricular-subventricular zone (V-SVZ), lining the lateral walls of the lateral ventricles, is a major neurogenic region in the adult brain of many mammals. This study investigates the structural organization and cellular composition of the V-SVZ in the juvenile swine brain (3-5 months), providing novel insights into neuroblast migration in gyrencephalic species. Using immunohistochemistry combined with transmission and scanning electron microscopy, we redefined the cytoarchitecture of the swine V-SVZ, identifying four distinct cellular layers.

Mitochondrial Unfolded Protein Response (mtUPR) Activation Improves Pathological Alterations in Cellular Models of Ethylmalonic Encephalopathy.

Ethylmalonic encephalopathy (EE) is a serious metabolic disorder that usually appears in early childhood development and the effects are seen primarily in the brain, gastrointestinal tract, and peripheral vessels. EE is caused by pathogenic variants in the gene that encodes the ETHE1 protein, and its main features are high levels of acidic compounds in body fluids and decreased activity of the mitochondrial complex IV, which limits energy production in tissues that require a large supply of energy. ETHE1 is a mitochondrial sulfur dioxygenase that plays the role of hydrogen sulfide (HS) detoxification, and, when altered, it leads to the accumulation of this gaseous molecule due to its deficient elimination.

Glioblastoma progression is hindered by melatonin-primed mesenchymal stromal cells through dynamic intracellular and extracellular reorganizations.

Glioblastoma (GBM) is the most fatal form of brain cancer and its treatment represents a persistent challenge. Mesenchymal stromal cells (MSCs) have been explored as therapeutic tools in cancer management owing to their tumor-homing abilities. However, their clinical application is limited due to the controversial role of MSCs in carcinogenesis.

Neural stem cell relay from B1 to B2 cells in the adult mouse ventricular-subventricular zone.

Neurogenesis and gliogenesis continue in the ventricular-subventricular zone (V-SVZ) of the adult rodent brain. V-SVZ astroglial cells with apical contact with the ventricle (B1 cells) function as neural stem cells (NSCs). B1 cells sharply decline during early postnatal life; in contrast, neurogenesis decreases at a slower rate.

Iron Accumulation and Lipid Peroxidation in Cellular Models of Nemaline Myopathies.

One of the most prevalent types of congenital myopathy is nemaline myopathy (NM), which is recognized by histopathological examination of muscle fibers for the presence of "nemaline bodies" (rods). Mutations in the actin alpha 1 () and nebulin () genes result in the most prevalent types of NM. Muscle weakness and hypotonia are the main clinical characteristics of this disease.

Polydatin and Nicotinamide Prevent Iron Accumulation and Lipid Peroxidation in Cellular Models of Mitochondrial Diseases.

Ferroptosis, an iron-dependent form of non-apoptotic cell death, is regulated by a complex network involving lipid metabolism, iron homeostasis, and the oxidative-reductive system, with iron accumulation and lipid peroxidation as key drivers. Mitochondrial dysfunction and ROS overproduction often underlie the pathogenesis of mitochondrial diseases, for which treatment options are limited, emphasizing the need for novel therapies. In this study, we investigated whether polydatin and nicotinamide could reverse ferroptosis-related pathological features in cellular models derived from patients with pathogenic variants.

Biotin Induces Inactive Chromosome X Reactivation and Corrects Physiopathological Alterations in Beta-Propeller-Protein-Associated Neurodegeneration.

Neurodegeneration with brain iron accumulation (NBIA) involves a group of rare neurogenetic disorders often linked with iron overload in the basal nuclei of the brain presenting with spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration. Among NBIA subtypes, beta-propeller-protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45 (WD repeat domain 45). Previously, we demonstrated that WDR45 mutations in BPAN cellular models impaired autophagy, iron metabolism, and cell bioenergetics.

Neural Stem Cell Relay from B1 to B2 cells in the adult mouse Ventricular-Subventricular Zone.

Neurogenesis and gliogenesis continue in the Ventricular-Subventricular Zone (V-SVZ) of the adult rodent brain. B1 cells are astroglial cells derived from radial glia that function as primary progenitors or neural stem cells (NSCs) in the V-SVZ. B1 cells, which have a small apical contact with the ventricle, decline in numbers during early postnatal life, yet neurogenesis continues into adulthood.

Neuraminidase inhibition promotes the collective migration of neurons and recovery of brain function.

In the injured brain, new neurons produced from endogenous neural stem cells form chains and migrate to injured areas and contribute to the regeneration of lost neurons. However, this endogenous regenerative capacity of the brain has not yet been leveraged for the treatment of brain injury. Here, we show that in healthy brain chains of migrating new neurons maintain unexpectedly large non-adherent areas between neighboring cells, allowing for efficient migration.

Identification of the growth cone as a probe and driver of neuronal migration in the injured brain.

Axonal growth cones mediate axonal guidance and growth regulation. We show that migrating neurons in mice possess a growth cone at the tip of their leading process, similar to that of axons, in terms of the cytoskeletal dynamics and functional responsivity through protein tyrosine phosphatase receptor type sigma (PTPσ). Migrating-neuron growth cones respond to chondroitin sulfate (CS) through PTPσ and collapse, which leads to inhibition of neuronal migration.

BCAS1 defines a heterogeneous cell population in diffuse gliomas.

Oligodendrocyte precursor markers have become of great interest to identify new diagnostic and therapeutic targets for diffuse gliomas, since state-of-the-art studies point towards immature oligodendrocytes as a possible source of gliomagenesis. Brain enriched myelin associated protein 1 (BCAS1) is a novel marker of immature oligodendrocytes and was proposed to contribute to tumorigenesis in non-central nervous system tumors. However, BCAS1 role in diffuse glioma is still underexplored.

Protracted neuronal recruitment in the temporal lobes of young children.

The temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs. The human EC continues to develop during childhood, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth.

Delayed maturation and migration of excitatory neurons in the juvenile mouse paralaminar amygdala.

The human amygdala paralaminar nucleus (PL) contains many immature excitatory neurons that undergo prolonged maturation from birth to adulthood. We describe a previously unidentified homologous PL region in mice that contains immature excitatory neurons and has previously been considered part of the amygdala intercalated cell clusters or ventral endopiriform cortex. Mouse PL neurons are born embryonically, not from postnatal neurogenesis, despite a subset retaining immature molecular and morphological features in adults.

Neurovascular unit disruption and blood-brain barrier leakage in MCT8 deficiency.

Background: The monocarboxylate transporter 8 (MCT8) plays a vital role in maintaining brain thyroid hormone homeostasis. This transmembrane transporter is expressed at the brain barriers, as the blood-brain barrier (BBB), and in neural cells, being the sole known thyroid hormone-specific transporter to date. Inactivating mutations in the MCT8 gene (SLC16A2) cause the Allan-Herndon-Dudley Syndrome (AHDS) or MCT8 deficiency, a rare X-linked disease characterized by delayed neurodevelopment and severe psychomotor disorders.

Antioxidants Prevent Iron Accumulation and Lipid Peroxidation, but Do Not Correct Autophagy Dysfunction or Mitochondrial Bioenergetics in Cellular Models of BPAN.

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic disorders frequently associated with iron accumulation in the basal nuclei of the brain. Among NBIA subtypes, β-propeller protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene . The aim of this study was to demonstrate the autophagic defects and secondary pathological consequences in cellular models derived from two patients harboring mutations.

Regulation of young-adult neurogenesis and neuronal differentiation by neural cell adhesion molecule 2 (NCAM2).

Adult neurogenesis persists in mammals in the neurogenic zones, where newborn neurons are incorporated into preexisting circuits to preserve and improve learning and memory tasks. Relevant structural elements of the neurogenic niches include the family of cell adhesion molecules (CAMs), which participate in signal transduction and regulate the survival, division, and differentiation of radial glial progenitors (RGPs). Here we analyzed the functions of neural cell adhesion molecule 2 (NCAM2) in the regulation of RGPs in adult neurogenesis and during corticogenesis.