Cellular and Molecular Events in Programmed Cell Death

Apoptosis & Phagocytosis

Programmed cell death (PCD), often referred to as cellular suicide, primarily occurs via a mechanism known as apoptosis, a term that comes from the Greek word meaning “a dropping away.” In contrast to necrosis, which represents an uncontrolled form of cell death, apoptosis is a carefully regulated process that plays a vital role in developing and maintaining the nervous system in multicellular organisms.

Morphological and Biochemical Features of Apoptosis

Pyknosis represents the first stage of programmed cell death (PCD), during which the cell passes through three distinct substages in preparation for its impending demise. First, the chromatin undergoes irreversible condensation, and nuclear material aggregates into crescent-shaped formations near the nuclear envelope. Under light microscopy, the nucleus is typically observed to be darkly shaded. Several distinct cellular events primarily drive this stage.

*insert figure 7.3 from Ch.7 Naturally Occurring Neuron Death*

The process begins with histone proteins, essential for organizing DNA into chromatin. Histone deacetylases (HDACs) remove acetyl groups from histones, restoring their natural positive charge. This change enhances the histones’ affinity for the negatively charged DNA, causing the chromatin to coil tightly and promoting compaction. Concurrently, a group of enzymes known as executioner caspases target and cleave membrane proteins that play a crucial role in maintaining membrane structure within the nuclear envelope. This cleavage disrupts the membrane’s integrity, triggering chromatin’s condensation.

Cell Shrinkage

• Influx of intracellular ions – Na+, K+, & Cl^–
• Cytoskeleton Collapse

Apoptotic bodies & Phagocytosis

Molecular Pathways of Neuronal Apoptosis

Intrinsic (Mitochondrial) Pathway

• Role of oxidative stress, Free Radicals and mitochondrial dysfunction
• Key regulators: Bcl-2 family proteins (pro-apoptotic vs. anti-apoptotic)
• Cytochrome c release and apoptosome formation
• Activation of caspase-9 and downstream caspase cascade

Extrinsic (Death Receptor) Pathway

• Death ligands (FasL, TNF-α, TRAIL) and receptor signaling
• Caspase !

Endoplasmic Reticulum and the Unfolded Protein Responses

Regulation of Apoptosis & Removal of Neurons

Inappropriate Neuron Death & Necrosis

Other Important Things to Probably Talk About

• Embryogenesis
• Use it or lose it metaphor
• Synaptogenesis & Synaptic Pruning
• Hormones, more proteins!, Cytokines, Neurotrophins, Calcium, Glutamate
• Autophagy!
• Hypoglycemia & Rapid Loss of Energy
• This is a cool video: https://www.youtube.com/watch?v=lZdj2Cm2tzk