Cholinergic neuron
Cholinergic neurons provide the primary source of acetylcholine to the cerebral cortex, and promote cortical activation during both wakefulness and rapid eye movement sleep.
[1] The cholinergic system of neurons has been a main focus of research in aging and neural degradation, specifically as it relates to Alzheimer's disease.
[2] The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in Alzheimer's disease.
[8] In the medial septum-diagonal band of Broca's area of the brain, cholinergic neurons have very low firing rates during both wake and non-REM sleep, and show no rhythmic bursts during hippocampal (theta) Electroencephalography activity.
However, cholinergic neurons in the magnocellular preoptic nucleus and Substantia innominata have increased firing rates with fast cortical (gamma) Electroencephalography activity during wake and rapid eye movement sleep.
Although degeneration of basal forebrain cholinergic cells has been observed in many other dementias, Alzheimer's has two distinctive histological hallmarks: Beta amyloid plaques and neurofibrillary tangles.
[3][12] There appears to be a vast, intrinsic microvascular pathology of the brain in these cases, which suggests a link between Beta amyloid production, impairments in cerebrovascular function, and basal forebrain cholinergic deficits in AD.
[2] It appears that Beta amyloid (1-42) mediates its cytotoxic action by affecting key proteins that play a role in apoptosis induction.
[7] Basal forebrain cholinergic neurons are highly dependent on the constant internal supply of Nerve Growth Factor throughout life.
If the supply of Nerve Growth Factor is interrupted, cholinergic atrophy could begin to occur in these neurons and change their phenotype.
This double failure of Nerve Growth Factor stimulation leads to the progressive atrophy of basal forebrain cholinergic neurons, which in turn contributes to Alzheimer's-related learning and memory declines.
In 2013, Dr. Su-Chun Zhang and his research team derived cholinergic neurons from neuroepithelial stem cells in a laboratory setting, making it easier to test potential treatments without the use of live animals.
This treatment is based on the theory that degenerative neural disorders have excitotoxic processes due to the inappropriate overstimulation of the NMDA receptor.
It should also be noted that memantine is able to inhibit the truncation of glycogen synthase kinase-3 (triggered by activated calpain), which is believed to play a key role in the pathogenesis of Alzheimer's, affecting tau phosphorylation (the second histological hallmark).
Cholinergic neurons have significantly reduced choline acetyltransferase and acetylcholine activity, which is correlated to the severity of the dementia or cognitive impairments.
[2][3][15] As with Alzheimer's, the degeneration of basal forebrain cholinergic neurons and the decrease in the neurotransmitter acetylcholine have a drastic effect on behavioral and cognitive function.
