Neurological Disorders and Neurodegenerative Diseases

Human narcolepsy is a chronic sleep disorder affecting about one in 2000 individuals. The disease is characterized by excessive daytime sleepiness, cataplexy and other abnormal manifestations of REM sleep, such as sleep paralysis and hypnagogic hallucinations. Hctr deficiencies, as shown by low or absent concentrations in CSF, were found in 90 of patients with sporadic narcolepsy-cataplexy and less commonly in familial narcolepsy. For example, Hctr-1 is undetectable in the CSF of most human...

Receptors and Signal Transduction

The ACh receptors consist of two major groups the muscarinic and the nicotin-ic receptors. They can be distinguished by their selectivity to the alkaloids nicotine and muscarine. Dale originally introduced this classification in 1914 and it is still valid, in spite of the fact that several subtypes of nicotinic and muscarinic receptors have been described meanwhile. The nicotinic receptors belong to the ligand-gated ion channel superfamily. This comprises the nicotinic receptor (neuronal and...

CB1 receptors

Cypin Guanine Deaminase Neurons

Genes encoding orthologs of the mammalian CB1 receptor have been identified in fishes, amphibians and birds, indicating that CB1 receptors may occur throughout the vertebrates. The genomes of the invertebrates Drosophila melano-gaster and Caenorhabditis elegans, however, do not contain CB1 orthologs, indicating that CB1-like cannabinoid receptors may have evolved after the divergence of deuterostomes and protostomes. The cDNA of the CB1-receptor is 5.7 kb in length and encodes for a putative...

Localization Within the Central Nervous System

Parabrachial Nucleus Projections

By means of immunohistochemical and radioimmunoassay techniques, CRF was found to be heterogeneously distributed throughout the central nervous system. Corticotropin-releasing factor is predominantly synthesized in the medial parvicellular neurons of the hypothalamic paraventricular nucleus (PVN), from which the majority of cells project to the median eminence. This CRF pathway comprises the hypothalamic portion of the endocrine stress axis. CRF is transported via the hypothalamo-pituitary...

Biosynthesis and Degradation

The synthesis of acetylcholine is straightforward and follows a simple scheme. ACh is synthesized from acetylCoA and choline by an enzyme known as cho-line acetyltransferase ChAT . The choline acetyltransferase is located almost exclusively in the cytoplasm of cholinergic fibers. Cholinergic neurons contain high concentrations of ChAT, indicating that this enzyme is not rate-limiting in the synthesis of acetylcholine. The acetyl-CoA which serves as a donor derives from pyruvate generated by...