Neurogenesis

…neuronal death and promoting neurogenesis. They act by binding to their respective high-affinity, pro-survival receptors TrkA, TrkB or TrkC, as well as to p75NTR death receptor. While these molecules have been shown to significantly slow or prevent neurodegeneration, their reduced bioavailability and inability to penetrate the blood-brain-barrier limit their use as potential therapeutics. To bypass these limitations, our research team has developed and patented small-sized, lipophilic

Neurogenesis, the process in which neural precursor cells differentiate into mature neurons, occurs also postnatally and is critical to cognitive processes such as learning and memory. A main neurogenic niche is located in the dentate gyrus of the hippocampus, a brain area greatly involved in learning and memory. During the normal process of aging, hippocampal neurogenesis decreases substantially, and it is suggested that this decrease starts at the very first stages, if not immediately prior to, the development of mild cognitive impairment and/or dementia. Unfortunately, despite the increasin

…ubiquitin ligase APC/C-Cdh1 promotes neurogenesis, proliferation, and neuronal survival, which are essential events for brain repair after stroke. APC-Cdh1 also regulates protein levels of the dendrite stabilizer Rock2. Thus, the APC/C-Cdh1-Rock2 axis modulates dendrite elongation and synaptogenesis. However, whether Cdh1 plays a role in stroke remain

Throughout development, the brain dynamically regulates the composition of its extracellular fluid compartments. Proteins secreted into these compartments, defined collectively as the brain secretome, have been shown to influence key neurodevelopmental processes from cell migration to synaptogenesis. Nonetheless, only a fraction of the brain secretome has been comprehensively characterized, leaving the developmental contribution of many disorder-associated secreted proteins unexplored. A growing body of literature highlights the dysregulation of extracellular fluids in the brain as a common fe

The entorhinal cortex lesion is a validated model for studying neuronal, dendritic and spine remodelling of dentate gyrus granule cells after denervation. Our research aims to investigate the effect of the layer-selective denervation of the dentate gyrus on the proliferation and differentiation of neurons in the granule cell layer, as the mechanisms that drive the remodelling due to the loss of input are not yet understood. Therefore, in anaesthetised adult male C57Bl/6 mice, the transection of the perforant pathway was performed, resulting in the layer-specific denervation of dentate granule

Metabolic Associated Fatty Liver Disease (MAFLD) has recently emerged as a major health concern in Western countries, being characterized by hepatic fat accumulation, altered metabolism, increased oxidative stress, and inflammation. This condition triggers the release of hormones, free radicals, and inflammatory mediators in blood, potentially affecting central nervous system. Unfortunately, limited studies have explored the impact of MAFLD on the brain and its potential association with neuronal metabolism and activity. In our study, we utilized preclinical MAFLD model induced by a six-week e

Methamphetamine (MA) is one of the most abused illicit drugs in the world. The abuse of this drug among adolescents is problematic due to the still developing physiological functions of the body, including the central nervous system (CNS). The hippocampus (HP) is a part of the limbic system that is associated with cognition, as well as the reward system, which is mediated by dopamine (DA). Disruption of this system is the basic mechanism underlying addiction and results in cognition deficiencies.In this work, we focused on the influence of MA on the development of the HP during postnatal days

Congenital hydrocephalus (CH) is a complex neurodevelopmental disorder characterized by enlarged brain ventricles and reduced cognitive functions. Here, we identified FLVCR1a (Feline Leukemia Virus Subgroup C Receptor 1) as a novel gene responsible for CH in humans. However, the molecular mechanism linking FLVCR1 loss to neurodevelopmental defects is still elusive. To clarify this, we generated mice lacking Flvcr1a in neural progenitor cells (NPCs) by using rat-Nestin promoter CRE model (NesCRE). Interestingly, the FLVCR1a fl/fl-NesCRE+ model recapitulates the main features of the human diseas

…brain by altering processes such as neurogenesis. ELS is known to impair adult hippocampal neurogenesis, however, the brain regions, cell types and underlying molecular mechanisms altered by ELS during development are unclear. Using an optogenetic zebrafish model to elevate stress hormone levels, we analysed the effects of ELS on neurogenesis during

Vitamin D deficiency (VDD) is a worldwide problem, especially among the elderly and epidemiological studies have found a link between VDD, cognitive decline and depression. However, it is unclear whether VDD directly drives the development of depression and cognitive decline or whether it is secondary to co-occurring pathology.In this study, we sought to determine whether long-term VDD causes memory impairments and depressive-like behavior alone or in combination with chronic stress and to elucidate co-occurring dysfunctions in neuronal and glial plasticity in the dentate gyrus (DG) of the hip

We investigated whether a synergistic effect would emerge in post-stroke treatment by opening the blood-brain barrier (BBB) with focused magnetic stimulation (MagStim) and delivering Atorvastatin-Loaded PEGylated Liposomes (LipoStatin). Two weeks after middle cerebral artery occlusion (MCAO), magnetic nanoparticles (MNP) were injected at a concentration of 15mg/ml, followed by 30 minutes of MagStim. The procedure was conducted over a week with MagStim, and magnetic nanoparticles (MNP) were injected three times at two-day intervals. After MagStim, LipoStatin at 10mg/kg was administered intraven

Brain L-serine is critical for neurodevelopment and is thought to be synthesized solely from glucose. In contrast, we found that the influx of L-serine across the blood–brain barrier (BBB) is essential for brain development. We identified the endothelial Slc38a5, previously thought to be a glutamine transporter, as an L-serine transporter expressed at the BBB in early postnatal life. Young Slc38a5 knockout (KO) mice exhibit developmental alterations and a decrease in brain L-serine and D-serine, without changes in serum or liver amino acids. Slc38a5-KO brains exhibit accumulation of neurotoxic

…determine the effect of galecitn-3 on neurogenesis and on glial clearance of Aβ. Neurospheres generated from primary murine neural stem cells were treated with galectin-3 or the galectin-3 inhibitor TD139. Proliferation, as determined by neurosphere size after 5 days, was decreased in neurospheres treated with galectin-3. Differentiation, as quantified by proportion o

…can affect neuron physiology, like neurogenesis, causing a depressive-like behavior. However, despite depression being twice as frequent in females, most studies have been done in males. This results in a gap in our current understanding of stress processing in both sexes, and consequently in our current therapeutical approach. Here, we used the social defeat stress (SDS) paradigm in 8-week-old male and female C57BL/6J mice for 10 consecutive days

Stroke is a leading cause of disability and death due to the brain’s limited ability to regenerate damaged circuits. Induced pluripotent stem cell (iPSC)-based therapies are emerging as a promising therapeutic approach for stroke recovery. Here, we demonstrate that local transplantation of GMP-compatible iPSC-derived neural progenitor cells (NPCs) improve long-term recovery-associated brain tissue responses and reduce neurological deficits after cerebral ischemia in mice. Using in vivo imaging and post-mortem histology, we showed long-term graft survival over the course of five weeks and prefe

…of anti-apoptosis, neurite growth and neurogenesis. In this study, we discovered that hPSC-EMSCs and hUC-MSCs expressed differential secreted factors by ut

…ablation (SCA) and HBO on processes of neurogenesis in the subventricular zone (SVZ), rostral migratory stream (RMS) and around the lesion site. The experiments were performed on adult male Wistar rats, ten weeks old. Animals were randomized into two g

Primary cilia receive extracellular signals and transmit them to the interior implementing signal transduction. These organelles enable the cell to communicate and realize essential processes such as proliferation and migration. Disruption of primary cilia signaling will lead to a multitude of human diseases called ciliopathies. Ciliopathies are often linked to malformations of the central nervous system. Abnormalities in cilia length are a parameter for inadequate function of primary cilia. Especially in situations when oxygen supply falls short, e.g. during an ischemic stroke, it is necessar

…that this pathway has key roles in neurogenesis, and mTORC1 hyperactivation during neurodevelopment causes a group of disorders known as mTORopathies. mTORopathies typically involve brain malformations and neurological manifestations like epilepsy. One example is tube

Huntington’s disease (HD) is a currently incurable neurodegenerative disorder that manifests itself through motor and cognitive symptoms due to a predominant loss of striatal projection neurons (SPNs) in the striatum. Although HD is a neurodegenerative disease, growing evidence show that developmental alterations could be a key factor in the disease, determining the future vulnerability of certain cell types, such as SPNs. Here we show an early HD-related gene expression pattern elucidated by bulk and single-cell RNA sequencing performed on wt and HD isolated mouse striatal primordia at differ

CDKL5 deficiency disorder (CDD) is an X-linked neurodevelopmental disorder caused by mutations in the CDKL5 gene. CDD is characterized by early-onset epilepsy, global developmental delay, intellectual disability, autistic features, visual impairment, and motor impairment. The CDKL5 gene is located on the X-chromosome and is highly expressed in the forebrain. Despite some molecular and cellular functions of CDKL5 being revealed, gaps and controversies still exist between different studies. The molecular actions of CDKL5 in human-derived neurons and the effects of CDKL5 disruption remain unclear

Neurogenesis is the process where neural stem cells (NSCs) develop into functional neurons. It comprises proliferation, differentiation, migration, axonal and dendritic targeting, and synaptic integration. Meropenem is a broad-spectrum carbapenem that treats various infections. It can penetrate most body fluids and tissues, cross the blood–brain barrier, and obtain a concentration within the cerebrospinal fluid close to that of blood plasma. However, no research has established a link between meropenem and neurotoxic effects on the brain and the subsequent behavioral activity. This project aim

The African naked mole rat (NMR) is an extremely long-lived species compared to its body size and can reach above 30 years of age. The NMR show unique adaptations to resist damage to the brain. They can survive up to 20 minutes of complete anoxia [1] and express high levels of amyloid-β without developing amyloid plaques [2]. Our aim is to understand if altered lipid metabolism through regulation of lipid droplets (LDs) in brain cells is one of the NMRs intrinsic adaptations, giving them their long-lived phenotype and resistance to neurological damage. Immunohistochemistry was performed on bra

…those affected by lactate, such as neurogenesis, synaptic