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Programmed cell death: implications for neuropsychiatric disorders
R L Margolis1, D M Chuang, R M Post
1Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD.
Abstract:
Programmed cell death, sometimes referred to as apoptosis, occurs through an active process requiring new gene transcription, in contrast to the passive cell death produced by metabolic toxins. Programmed cell death is an essential part of normal development, particularly in the nervous system. Spatial, temporal, or quantitative errors in the stimuli that initiate programmed cell death, or errors within the programmed cell death pathway itself, can result in an abnormal number of neurons and pathological neural development. Excesses and deficits in neuronal numbers have now been observed not only in typical neurodegenerative disorders such as Alzheimer's and Huntington's diseases, but also in several neurodevelopmental disorders, including schizophrenia and autism. Recent investigations into the mechanisms of cell death during C. elegans neurodevelopment thymocyte negative selection, and withdrawal of sympathetic ganglion cells trophic support provides intriguing clues to the etiology and pathophysiology of these neuropsychiatric disorders.
Insights
Programmed cell death, or apoptosis, is crucial for nervous system development. Errors in this process can lead to abnormal neuron numbers, contributing to neurodevelopmental and neurodegenerative disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Programmed cell death (apoptosis) is an active, gene transcription-dependent process distinct from passive cell death.
- It plays a vital role in normal development, especially within the nervous system.
- Dysregulation of programmed cell death contributes to various neurological conditions.
Purpose of the Study:
- To explore the role of programmed cell death in neural development.
- To investigate the connection between programmed cell death errors and neuropsychiatric disorders.
- To identify potential etiological and pathophysiological clues from model systems.
Main Methods:
- Investigated mechanisms of cell death during development.
- Examined processes like thymocyte negative selection in C. elegans.
- Studied the withdrawal of trophic support from sympathetic ganglion cells.
Main Results:
- Errors in programmed cell death initiation or execution lead to abnormal neuron numbers.
- Abnormal neuronal counts are observed in neurodevelopmental disorders (e.g., autism, schizophrenia) and neurodegenerative diseases (e.g., Alzheimer's, Huntington's).
- Insights from C. elegans and sympathetic neuron studies offer potential links to neuropsychiatric disorder mechanisms.
Conclusions:
- Programmed cell death is critical for normal neuronal development and number regulation.
- Disruptions in programmed cell death pathways are implicated in the pathophysiology of both neurodevelopmental and neurodegenerative diseases.
- Studying cell death mechanisms in model organisms provides valuable insights into human neuropsychiatric disorders.