Abstract
Cholinergic neurons in the central nervous system play a vital role in higher brain functions, such as learning and memory. Choline is essential for the synthesis of the neurotransmitter acetylcholine by cholinergic neurons. The synthesis and metabolism of acetylcholine are important mechanisms for regulating neuronal activity. Choline is a positively charged quaternary ammonium compound that requires transporters to pass through the plasma membrane. Currently, there are three groups of choline transporters with different characteristics, such as affinity for choline, tissue distribution, and sodium dependence. They include (I) polyspecific organic cation transporters (OCT1-3: SLC22A1-3) with a low affinity for choline, (II) high-affinity choline transporter 1 (CHT1: SLC5A7), and (III) choline transporter-like proteins (CTL1-5: SLC44A1-5). Brain microvascular endothelial cells, which comprise part of the blood–brain barrier, take up extracellular choline via intermediate-affinity choline transporter-like protein 1 (CTL1) and low-affinity CTL2 transporters. CTL2 is responsible for excreting a high concentration of choline taken up by the brain microvascular endothelial cells on the brain side of the blood–brain barrier. CTL2 is also highly expressed in mitochondria and may be involved in the oxidative pathway of choline metabolism. Therefore, CTL1- and CTL2-mediated choline transport to the brain through the blood–brain barrier plays an essential role in various functions of the central nervous system by acting as the rate-limiting step of cholinergic neuronal activity.
Highlights
Cholinergic neurons in the central nervous system play a vital role in higher brain functions, such as learning and memory
The and metabolism of choline is required for the synthesis of ofthe phospholipids phosphatidylcholine sphingomyelin), which are the main components phospholipids, which are the main components of the cell membrane and S-adenosylmethionine, which is a methyl group donor
We assessed whether choline uptake through both choline transporter-like protein 1 (CTL1) and CTL2 in human brain microvascular endothelial cells is used for acetylcholine synthesis and found that choline acetyltransferase (ChAT), AChE, and vesicular acetylcholine transporter (VAChT) mRNAs were not expressed, whereas BuChE was highly expressed, in these cells [36]
Summary
The blood–brain barrier restricts the exchange of substances (e.g., nutrients, drugs, and poison) between the blood vessels of the brain and brain cells, and helps maintain the optimal environment for nerve function. The blood–brain barrier is composed of brain microvascular endothelial cells, astrocytes, and pericytes. Highly water-soluble substances have difficulty crossing the blood–brain barrier, nutrients (e.g., glucose, amino acids, peptides, and nucleotides) selectively cross this barrier using various solute-carrier transporters (SLC transporters) that are expressed in the brain microvascular endothelial cells. Transporters endothelial expressed in brain ofcells the soluble (SLC)Many transporters expressed in brain microvascular cells allow microvascular endothelial cells allow substances, such as nutrients (e.g., glucose, amino substances, such as nutrients (e.g., glucose, amino acids, peptides, and nucleotides), to selectively cross acids, peptides, and nucleotides), to selectively cross the blood–brain barrier. Transporters that are ATP binding cassette (ABC) transporters thatinare expressed cerebral microvascular cerebral microvascular endothelial cells play a role preventing theinentry of toxic substances and endothelial cells play a role in preventing the entry of toxic substances and drugs into the drugs into the brain by releasing them into the blood.
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