Neurons are specialized cells that transmit electrical and chemical signals, forming the complex circuitry underlying all thought and movement. For much of the 20th century, the established view was that mature neurons are permanent cells that cannot divide or replicate after reaching their final form. While this rule holds true for the vast majority of cells in the adult brain, modern discoveries have revealed a surprising nuance to this concept.
The Post-Mitotic State: Why Neurons Do Not Divide
The inability of most mature neurons to replicate stems from a distinct biological decision made early in their development. Unlike skin or blood cells, which are constantly cycling and dividing, neurons are considered terminally differentiated. This means they have committed to their specialized function and permanently exited the cell division cycle, a state known as being post-mitotic.
This permanent withdrawal from the cycle is characterized by the cell entering the G0 phase. The G0 phase is a quiescent or resting state, where the cell performs its function without preparing for division. Neurons remain fixed in this terminal G0 state, prioritizing the maintenance of intricate, long-lasting connections over the ability to proliferate.
The cellular machinery required for division, such as the centrioles and various cell cycle proteins, is suppressed or disassembled in mature neurons. This suppression allows the neuron to dedicate resources to maintaining complex axonal and dendritic structures. Attempting to divide would risk severing these connections and dismantling the neural network.
The Exception: Neurogenesis in the Adult Brain
Neurogenesis is the process of generating new neurons and is the primary exception to the post-mitotic rule. It does not involve the replication of existing mature neurons but rather the activation and differentiation of neural stem cells or progenitor cells. This process is highly restricted in the adult human brain, occurring primarily in two specific locations.
The most recognized region for adult neurogenesis is the subgranular zone (SGZ) of the hippocampus, a structure associated with memory and learning. Here, neural stem cells divide and mature into new granule neurons that integrate into the existing circuitry. These new neurons are thought to play a role in complex memory formation and the regulation of mood.
The second region is the subventricular zone (SVZ) of the lateral ventricles. In many mammals, cells born in the SVZ migrate to the olfactory bulb, differentiating into interneurons involved in the sense of smell. The SVZ remains a reservoir of neural stem cells.
Clarifying Cell Division in the Brain: Neurons vs. Glial Cells
Confusion about cell division arises because the brain is capable of extensive cell proliferation, but this division is carried out by glial cells, not mature neurons. Glial cells are the non-neuronal support cells of the nervous system and far outnumber neurons in many regions.
The main types of glial cells are capable of mitosis and replication throughout life:
- Astrocytes provide structural support and nourishment.
- Oligodendrocytes create the insulating myelin sheath around axons.
- Microglia act as the brain’s resident immune cells, actively dividing and migrating to areas of damage or infection.
When the brain sustains an injury, the resulting scar tissue is largely formed by the proliferation of astrocytes, a process called gliosis. This rapid division of glial cells is a form of repair, isolating the damaged area, but it does not replace lost neurons.
Implications for Injury Recovery and Regeneration
The limited capacity for neurogenesis affects recovery from brain injuries, such as stroke or traumatic brain injury (TBI). Since lost neurons cannot be replaced by the division of mature cells, functional recovery relies on other mechanisms. The primary method is neuroplasticity, where the remaining neural circuitry reorganizes itself by forming new connections or strengthening existing ones.
Neuroplasticity is often insufficient to fully restore function. This hurdle has driven research into leveraging the brain’s latent regenerative potential. Scientists are investigating methods to stimulate neural stem cells in the hippocampus and SVZ to increase neurogenesis and direct new neurons to damaged areas.
Another promising avenue involves transplanting external stem cells into the injury site. The goal is to provide a source of new neurons or cells that secrete growth factors to promote the survival and connectivity of existing neurons. Overcoming the post-mitotic nature of most brain cells is the focus of regenerative medicine, aiming to replace lost tissue rather than simply relying on the existing circuitry to rewire.