The Role of Astrocytes in the Molecular Pathophysiology of Schizophrenia: Between Neurodevelopment and Neurodegeneration Article Swipe
Licia Vellucci
,
Benedetta Mazza
,
Annarita Barone
,
Annamaria Assunta Nasti
,
Giuseppe De Simone
,
Felice Iasevoli
,
Andrea de Bartolomeis
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/biom15050615
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/biom15050615
Schizophrenia is a chronic and severe psychiatric disorder affecting approximately 1% of the global population, characterized by disrupted synaptic plasticity and brain connectivity. While substantial evidence supports its classification as a neurodevelopmental disorder, non-canonical neurodegenerative features have also been reported, with increasing attention given to astrocytic dysfunction. Overall, in this study, we explore the role of astrocytes as a structural and functional link between neurodevelopment and neurodegeneration in schizophrenia. Specifically, we examine how astrocytes contribute to forming an aberrant substrate during early neurodevelopment, potentially predisposing individuals to later neurodegeneration. Astrocytes regulate neurotransmitter homeostasis and synaptic plasticity, influencing early vulnerability and disease progression through their involvement in Ca2⁺ signaling and dopamine–glutamate interaction—key pathways implicated in schizophrenia pathophysiology. Astrocytes differentiate via nuclear factor I-A, Sox9, and Notch pathways, occurring within a neuronal environment that may already be compromised in the early stages due to the genetic factors associated with the ‘two-hits’ model of schizophrenia. As a result, astrocytes may contribute to the development of an altered neural matrix, disrupting neuronal signaling, exacerbating the dopamine–glutamate imbalance, and causing excessive synaptic pruning and demyelination. These processes may underlie both the core symptoms of schizophrenia and the increased susceptibility to cognitive decline—clinically resembling neurodegeneration but driven by a distinct, poorly understood molecular substrate. Finally, astrocytes are emerging as potential pharmacological targets for antipsychotics such as clozapine, which may modulate their function by regulating glutamate clearance, redox balance, and synaptic remodeling.
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Metadata
- Type
- review
- Language
- en
- Landing Page
- https://doi.org/10.3390/biom15050615
- https://www.mdpi.com/2218-273X/15/5/615/pdf?version=1745474976
- OA Status
- gold
- Cited By
- 6
- References
- 330
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409729458
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409729458Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/biom15050615Digital Object Identifier
- Title
-
The Role of Astrocytes in the Molecular Pathophysiology of Schizophrenia: Between Neurodevelopment and NeurodegenerationWork title
- Type
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reviewOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
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2025-04-23Full publication date if available
- Authors
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Licia Vellucci, Benedetta Mazza, Annarita Barone, Annamaria Assunta Nasti, Giuseppe De Simone, Felice Iasevoli, Andrea de BartolomeisList of authors in order
- Landing page
-
https://doi.org/10.3390/biom15050615Publisher landing page
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-
https://www.mdpi.com/2218-273X/15/5/615/pdf?version=1745474976Direct link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.mdpi.com/2218-273X/15/5/615/pdf?version=1745474976Direct OA link when available
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Neurodegeneration, Neuroscience, Schizophrenia (object-oriented programming), Pathophysiology, Medicine, Psychology, Disease, Psychiatry, PathologyTop concepts (fields/topics) attached by OpenAlex
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6Total citation count in OpenAlex
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2025: 6Per-year citation counts (last 5 years)
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330Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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