Related Experiment Video
Updated: Aug 13, 2026
12:06
Optic Nerve Transection: A Model of Adult Neuron Apoptosis in the Central Nervous System
Published on: May 12, 2011
Ontogenic cell death in the nigrostriatal system
1Department of Neurology, The College of Physicians and Surgeons, Columbia University, 650 West 168th Street, New York, NY 10032, USA. rb43@columbia.edu
Cell and Tissue Research
|September 7, 2004
Summary
Glial cell line-derived neurotrophic factor (GDNF) supports dopamine neuron survival during early development. However, other factors influence the final number of dopamine neurons in adulthood, crucial for Parkinson's disease therapies.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Death Research
Background:
- Dopamine neurons in the substantia nigra undergo programmed cell death during development.
- This process is biphasic, with peaks shortly after birth and around postnatal day 14.
- Striatal target interactions regulate this cell death, influencing adult neuron numbers.
Purpose of the Study:
- To investigate the role of striatal target-derived neurotrophic factors in dopamine neuron development.
- To identify the specific factors involved in regulating programmed cell death of dopamine neurons.
- To understand mechanisms influencing the mature number of nigral dopamine neurons for potential therapeutic applications.
Main Methods:
- Utilized rodent models to study developmental cell death of dopamine neurons.
- Investigated the effects of glial cell line-derived neurotrophic factor (GDNF) via intrastriatal injections and neutralizing antibodies.
- Employed a double transgenic mouse model for sustained striatal GDNF overexpression during development.
Main Results:
- GDNF acts as a physiological neurotrophic factor during the initial phase of dopamine neuron cell death.
- Intrastriatal GDNF administration reduced cell death, while antibodies increased it.
- Sustained GDNF overexpression increased neuron survival in the first phase but not into adulthood.
Conclusions:
- GDNF is critical for early developmental survival of dopamine neurons.
- Mechanisms beyond GDNF regulate the final number of dopamine neurons surviving into adulthood.
- Further research into these mechanisms is vital for developing Parkinson's disease therapies.
Related Concept Videos
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:18Autophagic Cell Death
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
01:16Necrosis
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
01:15Neurogenesis and Regeneration of Nervous Tissue
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
01:11Cellular Injury IlI: Cellular Death
Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...