About this Research Topic
The incidence and prevalence of neurological diseases, especially neurodevelopmental and neurodegenerative diseases (NDDs) affecting the CNS, have increased markedly over the years. It is commonly believed that multiple factors, including age, environment, genetics, and immunity contribute to their development.
Studies have suggested that primary astrocyte dysfunction may underlie certain disorders, including Autism Spectrum Disorders (ASD), Rett syndrome, Schizophrenia, Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and stroke.
Under normal physiological conditions, astrocytes outnumber other cell types in the CNS, critically contributing to brain homeostasis. In pathology, early astrocytic alterations can affect the release of neurotransmitters, neurogenic niches, neuroinflammatory response, synaptic plasticity, extracellular homeostasis, and the blood-brain barrier (BBB) integrity.
Recent advances in cellular and molecular biology, genetic and pharmacological studies have expanded our knowledge of the role of astrocytes in neurodevelopmental and neurodegenerative diseases. Some studies suggest that astrocytes may be able to trigger the pathology, suggesting a need to better understand their positive and negative impacts on the progression of the disease.
Targeting astrocytes thus has a potential for developing new strategies for treating neurodegenerative diseases. Recent in vitro studies have investigated the interplay between neurons and astrocytes in ASD by using ASD-derived astrocytes in combination with neuronal cultures.
These studies point to an interfering role of astrocytes in proper neuronal development and synaptogenesis.
ALS pathogenesis studies suggest that dysfunctional astrocytes contribute to the damage of motor neurons in a non-cell autonomous fashion. In this scenario, dysfunctional astrocytes display increased intracellular levels of NO synthase. This then promotes increased NO release from cell soma while glutamate uptake decreases at the synaptic cleft level of the spinal cord.
While there are controversial reports dealing with the role of astrocytes in AD pathology, astrocytes are important players in clearing the amyloid deposition in the brain via uptake and amyloid-β degradation. As the disease progresses, however, clearance levels are reduced and an amyloid-β accumulation leads astrocytes to activate and allows for a pro-inflammatory response.
Astrocytes, partnered with other glial cells contribute to neuroinflammatory response in AD brains by releasing proinflammatory cytokines, chemokines, and other factors.
In the case of stroke, astrocytes constitute an essential part of the neuroinflammatory response in the brain. Reactive astrogliosis accompanies multiple stages of stroke progression.
During the acute phase, astrocyte reactivity is triggered by the initial burst of pro-inflammatory signals.
The transition into the post-acute stroke phase is signified by the glial scar formation, demarcating the lesion site, and initiating brain remodeling.
Recent evidence indicates that reactive astrocytes adopt several distinct modes of activation, spanning from protective to detrimental profiles. In context with post-stroke recovery, these mechanisms are highly relevant for the development of novel restorative therapies.
Overall, regulating the function of astrocytes and identifying novel molecular targets of astrocytes, may modulate disease progression and thus help us to understand the pathophysiological basis underlying the reactivation of astrocytes which is essential when it comes to developing potential treatments for the future.
This Research Topic aims to broaden our current knowledge of astrocytic involvement in the progress of NDDs’ pathogenesis, reactive astrocyte properties in ischemic stroke conditions, and possible therapeutic strategies involving astrocytes as key players.
We welcome research articles covering broad areas of these disorders, from clinical trials to pre-clinical studies and via different experimental setups, both in vitro and in vivo, in different animal models and tissue cultures.
We also welcome the submission of reviews summarizing the recent progress and case reports relevant to this topic, in particular, rare astrocyte-related conditions, such as astrocytopathy in epilepsy, and astrocyte inclusion in neurodevelopmental disorders.
Potential topics include, but are not limited to:
• Identification of novel mechanism of astrocytic involvement in NDDs
• Experimental evidence from rare astrocyte-related diseases such as astrocytopathy
• Astrocytes’ involvement in NDD related synaptic defects, and insights extricating the mechanisms underlying synaptic loss and defects (tripartite synapse, non-cell autonomous effects, and neuroinflammation)
• Exploring the beneficial and detrimental properties of reactive astrocytes in NDDs
• Exploring possible and promising treatment options for NDDs through astrocyte targeting
Keywords: Astrocytes, Neurodevelopmental diseases, Neurodegenerative diseases, Ischemic Stroke, Reactive Astrocytes, Therapeutic Strategies
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