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Published on: March 23, 2011
Changes in molecular composition of rat medial prefrontal cortex synapses during adolescent development
Danielle S Counotte1, Ka Wan Li, Joke Wortel
1Department of Molecular and Cellular Neurobiology, Center for Neurogenomics & Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
Adolescent brain development involves significant synapse changes. Proteomics reveals distinct protein shifts in rat medial prefrontal cortex synapses during this critical period, highlighting changes in synaptic vesicle and release machinery proteins.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Postnatal brain development extends through adolescence, a period marked by synapse strengthening and elimination.
- Molecular insights into late-stage synaptic development, particularly during adolescence, remain limited.
Purpose of the Study:
- To investigate the molecular composition of synaptic membranes during adolescent rat brain development.
- To identify protein expression changes in the medial prefrontal cortex from early to late adolescence and into adulthood.
Main Methods:
- Isobaric tag for relative and absolute quantification (iTRAQ)-based proteomics was employed.
- Electron microscopy was used to analyze synaptic structures.
- Proteomic analysis was performed on synaptic membrane fractions from rats at postnatal days 34, 44, and 78.
Main Results:
- Significant protein expression differences were observed between early adolescence and young adulthood (35%).
- Cell-membrane proteins were over-represented during early adolescent development (P34-P44), while synaptic vesicle proteins increased between late adolescence and adulthood (P44-P78).
- A substantial 14% of proteins were differentially expressed between P34 and P44, indicating a critical developmental window, with non-stoichiometric regulation of synaptic vesicle and release machinery proteins.
Conclusions:
- Synaptic molecular composition, especially the release machinery, undergoes drastic changes during adolescent development in the rat medial prefrontal cortex.
- Adolescence represents a critical period for synaptic molecular refinement, with distinct protein classes regulated non-stoichiometrically.
- Electron microscopy showed minimal changes in docked and total synaptic vesicles during this period, suggesting molecular regulation precedes significant structural changes.
