Granule Cell - Role in Disease

Role in Disease

  • Altered morphology of dentate granule cells

TrkB is responsible for the maintenance of normal synaptic connectivity of the dentate granule cells. TrkB also regulates the specific morphology (biology) of the granule cells and is thus said to be important in regulating neuronal development, neuronal plasticity, learning, and the development of epilepsy. The TrkB regulation of granule cells is important in preventing memory deficits and limbic epilepsy. This is due to the fact that dentate granule cells play a critical role in the function of the entorhinal-hippocampal circuitry in health and disease. Dentate granule cells are situated to regulate the flow of information into the hippocampus, a structure required for normal learning and memory.

  • Decreased granule cell neurogenesis

Both epilepsy and depression show a disrupted production of adult-born hippocampal granule cells. Epilepsy is associated with increased production - but aberrant integration - of new cells early in the disease and decreased production late in the disease. Aberrant integration of adult-generated cells during the development of epilepsy may impair the ability of the dentate gyrus to prevent excess excitatory activity from reaching hippocampal pyramidal cells, thereby promoting seizures. Long-lasting epileptic seizure stimulate dentate granule cell neurogenesis. These newly born dentate granule cells may result in aberrant connections that result in the hippocampal network plasticity associated with epileptogenesis.

  • Shorter granule cell dendrites

Patients suffering from Alzheimer's have shorter granule cell dendrites. Furthermore, the dendrites were less branched and had fewer spines than those in patients not suffering with Alzheimer's. However, granule cell dendrites are not an essential component of senile plaques and these plaques have no direct effect on granule cells in the dentate gyrus. The specific neurofibrillary changes of dentate granule cells occur in patients suffering from Alzheimer's, Lewy body variant and progressive supranuclear palsy.

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