Roadmap for Postnatal Brain Maturation: Changes in Gray and White Matter Composition during Development Measured by...

Area of Science:

• Neuroscience
• Biochemistry
• Biophysics

Background:

• Postnatal brain development involves critical changes in gray and white matter (GM and WM), including myelination.
• Understanding these compositional shifts is vital for characterizing normal brain formation and neurodevelopmental disorders like autism and schizophrenia.

Purpose of the Study:

• To investigate chemical changes during postnatal brain myelination using Fourier transform infrared (IR) microspectroscopy (μFTIR).
• To correlate μFTIR data with histochemical and immunohistochemical staining for lipids and myelin proteins in developing mouse brains.

Main Methods:

• Analysis of mouse brain (C57BL/6) GM and WM from postnatal day 0 to P28.
• Combined histochemical staining, immunohistochemical staining, and μFTIR analysis.
• μFTIR used to quantify lipid/protein ratios, assess lipid chemical characteristics, and determine protein secondary structures.

Main Results:

• μFTIR's CH2/amide I ratio correlated well with lipid accumulation during myelination.
• Lipid composition in white matter changed, with no increase in carbonyl or unsaturated olefinic groups during lipid accumulation.
• Myelin oligodendrocyte protein correlated with lipid accumulation, while myelin basic protein preceded lipid changes, indicating asynchronous protein and lipid deposition.

Conclusions:

• Primary myelination significantly alters WM lipid and protein composition.
• Lipid histochemical staining provides a better description of these modifications than immunohistochemistry for myelin-related proteins.
• μFTIR is a valuable tool for studying WM development and identifying chemical alterations linked to neurodevelopmental diseases.