What Symptoms or Behaviors Are Associated With Acetylcholine When It Is Deficient And/Or Excessive?
Acetylcholine is a chemical that is found between the nerve synapses, or gaps, between nerve cells. When activated, it causes the contraction of skeletal muscles and activates glandular functions in the endocrine system. Think of acetylcholine as a mailperson; residents cannot receive their mail until he or she comes and delivers it to the mailbox. Like mailpersons who deliver the mail and move on to the next house, acetylcholine acts quickly and does not hang around. As a result, acetylcholine is rapidly broken down by another chemical substance called cholinesterase.
Despite it’s role in the CNS and stimulating parasympathetic activity, there is very little info about choline and mental illness. However, in a large population-based study published in The American Journal of Clinical Nutrition, people with higher blood levels of choline had lower levels of anxiety – however, levels of choline did not correlate with depressive symptoms. Despite the lack of studies, it has been clinically observed that supplementing Lecithin or putting patients on a Lecithin rich diet can lower levels of anxiety, help the nervous system by establishing balance between sympathetic and parasympathetic, and even manage cardiac dysrhthmias. The Milner Acetylcholine Protocol (MAP) uses lecithin to manage cardiac dysrhthmias. The fundamental building blocks of all cell membranes are phospholipids. Lecithin consists of phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, Phosphatidic acid, other minor phospholipids and glycolipids. About 50% of the mass of most cell membranes are composed of phospholipids. The plasma membranes of cells also contain glycolipids and cholesterol – which correspond to about 40% of the total lipid molecules. Adequate intake of phospholipids and glycolipids is important for the integrity of the cell membranes. Lecithin contains a balanced amount of phospholipids and glycolipids.
ACh that is synthesized in the cytoplasm of cholinergic neurons is transported into synaptic vesicles by VAChT, which is located in the synaptic vesicle membrane (Tagliavini F., Pilleri G., 1984). The gene encoding VAChT has been cloned and hydrophobic analysis indicates that the protein has twelve transmembrane domains. Each molecule of ACh transported by VAChT is in exchange for two vesicular protons, which leads to the fulfill of synaptic vesicles with the neurotransmitter. The vesicular transporter activity can be blocked by vesamicol, which is a non-competitive inhibitor. VAChT carboxyl-terminus has many motifs important for cellular trafficking and for its localization to synaptic vesicle membranes. Interestingly, PKC can phosphorylate VAChT and regulate its vesicular localization (Kish S.J., el-Awar M., 1988). A VAChT knockdown mouse model, expressing about 68% less VAChT protein, shows major neuromuscular deficits. This data highlights the importance of the transporter to the peripheral nervous system. Furthermore, cognitive impairment can take place even due to a mild decrease in VAChT protein expression (about 45%).
In summary, despite decades of work, a complete understanding of the role of ACh in brain function remains elusive. However, recent methodological advances for monitoring and manipulating cholinergic systems have broadened our knowledge of the cellular mechanisms underlying ACh signaling. Similarly, new human imaging studies have highlighted the role for distinct cholinergic systems in behavior. One principal conclusion to be drawn from the wealth of current data is that cholinergic modulation is best viewed as the synergistic alteration of neuronal function at the synaptic, cellular, and network levels.
Tagliavini F., Pilleri G., Bouras C., Constantinidis J. The basal nucleus of Meynert in patients with progressive supranuclear palsy. Neurosci. Lett. 1984
Kish S.J., el-Awar M., Schut L., Leach L., Oscar-Berman M., Freedman M. Cognitive deficits in olivopontocerebellar atrophy: implications for the cholinergic hypothesis of Alzheimer’s dementia. Ann. Neurol. 1988
Ferrante R.J., Beal M.F., Kowall N.W., Richardson E.P., Jr, Martin J.B. Sparing of acetylcholinesterase-containing striatal neurons in Huntington’s disease. Brain Res. 1987