Topic: reactive astrogliosis

Air pollution is a significant threat to human health and it is estimated that globally 8.9 million deaths happen because of it. A link between urban particulate matter exposure and an increased risk of neurodegenerative disease has already been identified. For this reason, I used wild-type hiPSCs to set up a 2D differentiation protocol of about 70 days. Cultures were untreated or treated with two doses of manganese, 1 μM and 20 μM, chosen in relation to scientific literature and after a MTS viability assay. Treatments started from day 40 until the end of differentiation (intermediate time poi

Tauopathy is a hallmark of a broad category of neurodegenerative conditions and Traumatic Brain Injury (TBI). Progression of tau pathology may lead to impaired cognitive conditions leading to dementia. However, previous studies have reported cognitively healthy patients with cortical tau pathologies. The mechanism for this cognitive protection in a tauopathy environment is being investigated by various groups. Astrocytes are essential for physiological homeostasis of brain and reactive astrogliosis is an associated pathology in neuroinflammation associated with TBI. The correlation between lev

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that causes the degeneration of motor neurons in the motor cortex and spinal cord. Patients with ALS experience muscle weakness and atrophy in the limbs which eventually leads to paralysis and death. NAD+ is critical for energy metabolism, such as glycolysis and oxidative phosphorylation, but is also involved in non-metabolic cellular reactions. In the current study, we determined whether the supplementation of nicotinamide mononucleotide (NMN), an NAD+ precursor, in the diet had beneficial impacts on disease progr

Medial temporal lobe epilepsy (MTLE) is a common cause of treatment-resistant seizures where excessive and hyper-synchronized neuronal activity is associated with reactive astrogliosis. Emerging evidence has indicated a role for neuron-astrocyte interactions in seizure activity. Previous studies have found increased astrocyte Ca2+ signals in mouse models for MTLE, but it has been difficult to disentangle how these drive or mitigate seizure activity in chronic epilepsy. We used an AAV8-GFAP-hM3Dq-mCherry vector to manipulate reactive astrocytes in the chronic phase of the mouse intrahippocampal

Communication between neurons and glial cells are crucial to establish and maintain brain function. Some of these interactions are activity-dependent, yet it remains unexplored how acute changes in neuronal activity affect neuron-to-glial dynamics.Here, we used excitatory and inhibitory designer receptors exclusively activated by designer drugs (DREADD) based chemogenetic methods to study the effects of acute manipulations of a subpopulation of layer 5 cortical projection and dentate gyrus neurons in adult (Rbp4Cre) mouse brain after 90 minutes. We validated changes in activity with in vitro p

Astrocytes are rapidly gaining ground as important regulators and potential therapeutic targets in neurodegeneration. Here, we used the cuprizone model of multiple sclerosis to explore the phenotypic signature of astrocytes in the cortex of mice during early demyelination at week 3 (CPZ3), a timepoint of initial demyelination and glia cell activation. Confocal imaging combined with detailed cell-morphometric analysis of cortical astrocytes after 3-dimensional cell reconstruction revealed the morphological phenotype of astrocytes in early demyelination, characterized by thick and long processes

CETN2 is a centrosomal, calcium-binding protein implicated in mitosis and DNA repair best known for its expression in photoreceptors and ciliated cells. Here, we took advantage of a culture of human neuroepithelial stem (NES) to determine its expression in other cell types of the nervous tissue. We confirmed CETN2 centrosomal location in proliferating NES cells, and pointed out its relocation along with the differentiation process describing its cytoplasmic distribution in human astrocytes, while being absent in all other cell types. Next, we questioned about CETN2 role in pathologies in which

Stroke is a leading cause of adult disability and the third leading cause of death. Despite expanding reperfusion treatment indications, a significant proportion of patients (54.5%) experience poor outcomes despite successful recanalization, emphasizing the need for a clinically relevant preclinical stroke model. In response, we developed a novel mouse model involving photothrombotic (PT) occlusion and light-induced recanalization of the distal branch of the middle cerebral artery (MCA), closely mimicking ischemic progression in clinical settings.The stable occlusion of the MCA's distal branch

After spinal cord injury (SCI), astrocytes become reactive in a process called astrogliosis. These reactive astrocytes surround the lesion and form an astrocyte scar border. Our lab recently previously discovered that LZK (or MAP3K13) regulates reactive astrogliosis and scar formation after a dorsal spinal cord crush injury. The effect of LZK-mediated astrogliosis on neural repair and regeneration is still not clear. We aim to investigate this question utilizing genetically modified mice and RNA sequencing. We are testing the effect of astrocytic LZK overexpression or deletion on behavioral re