Peptides

The development of diverse antisera for a variety of peptides augmented the tool kit of chemical neuroa-natomy. Neuropeptides are largely neuron-specific chemical compounds that, depending on the neuro-peptide, are characteristic of specific neuronal subgroups. For example, vasopressin is characteristic of large cells in the lateral magnocellular subnucleus of the paraventricular hypothalamic nucleus. The neuro-peptides are widely distributed and numerous, and for the sake of nomenclature they have been classified into families. For example, tachykinins (literally "fast acting'') constitute a family of small, structurally related peptides that share a similar carboxy-terminal sequence but differ with respect to their function and distribution. The distribution of substance P, the most widely known tachykinin, was useful for the differentiation of four of nine subnuclei of the dorsal motor nucleus of the vagus nerve. Within these subnuclei, substance P staining revealed three different types of neurons. The neuropeptides, of course, are likely to be products of neuronal metabolism and thus a reflection of functional characteristics of the particular neurons. This does not mean that all the peptides are neuro-transmitters or neuromodulators, but it does imply that the neuropeptide "alphabet" can be used for chemical coding of the neuronal groups that serve similar functions and are characterized by similar projections. In the Rosetta stone Greek was the common denominator between hieroglyphics and English. Likewise, the presence of a neuroactive substance in similar locations in the rat and the human brain can betray a structural homology.

The corticotropin-releasing factor (CRF) (or hormone) is a neuroendocrine peptide found in the cortex, basal telencephalon, brain stem, and hypothalamus. The best known function of CRF is to initiate the response in the hypothalamo-pituitary-adrenal axis, but it is also implicated in stress responses, metabolic regulation, and food intake. Recent studies have found increases in the number of CRF-positive neurons in the human hypothalamus with age. Another report showed colocalization of CRF with nitric oxide synthase in a subgroup of cells in the human hypothalamus and suggested the possible involvement of these neurons in schizophrenia and depression. The distribution of CRF is very specific. Thus, in neuroanatomy CRF distribution has been used in the human brain to distinguish the subcompartmental organization of specific nuclei in the medulla and hypothalamus. For example, in the paraventricular hypothalamic nucleus, CRF neurons are confined to the parvicellular compartment, whereas the neurons that contain oxytocin are found primarily in the dorsal compartment. Applying these two markers to the same brain allowed researchers to distinguish between these subcompart-ments, which otherwise appear to be amalgamated, and it also allowed the establishment of subcompart-mental homologies between human and rat paraven-tricular nucleus (Figs. 2 and 7).

Figure 3 Photomicrographs of coronal sections through the human (A and B), monkey (C), and rat (D) anterior hypothalamus processed enzymatically and immunohistochemically for (A) AChE and (B) SMI32 showing complimentary distribution of these substances and revealing the three constituent subnuclei of the MPO. Sections in A and B are virtually adjacent. In all three species the lateral subnucleus of the medial preoptic nucleus (MPOL) contains SMI32 immunorecative neuropil, whereas the medial MPO (MPOM) is SMI32 negative. Acetylcholinesterase reactivity also reveals the celebrated sexually dimorphic (or intermediate InM) nucleus. Scale bar=1 mm (C) and 0.5 mm (D).

Figure 3 Photomicrographs of coronal sections through the human (A and B), monkey (C), and rat (D) anterior hypothalamus processed enzymatically and immunohistochemically for (A) AChE and (B) SMI32 showing complimentary distribution of these substances and revealing the three constituent subnuclei of the MPO. Sections in A and B are virtually adjacent. In all three species the lateral subnucleus of the medial preoptic nucleus (MPOL) contains SMI32 immunorecative neuropil, whereas the medial MPO (MPOM) is SMI32 negative. Acetylcholinesterase reactivity also reveals the celebrated sexually dimorphic (or intermediate InM) nucleus. Scale bar=1 mm (C) and 0.5 mm (D).

Figure 4 Photomicrographs of adjacent coronal sections through the human hypothalamus (demonstrating differential distribution of NPH-positive fibers (A) and neuropeptide Y (NPY)-positive cells and fibers (B). Immunoreactivity reveals details of intrinsic organization of the arcuate hypothalamic nucleus. (C) First appearance of NPY-positive neurons in the arcuate nucleus at 21 weeks of gestation. (D) Area of arcuate nucleus in B at higher magnification showing a population of morphologically developed NPY-positive neurons. (Reproduced from J. Comp. Neurol. with permission from John Wiley & Sons, Inc., 2002).

Figure 4 Photomicrographs of adjacent coronal sections through the human hypothalamus (demonstrating differential distribution of NPH-positive fibers (A) and neuropeptide Y (NPY)-positive cells and fibers (B). Immunoreactivity reveals details of intrinsic organization of the arcuate hypothalamic nucleus. (C) First appearance of NPY-positive neurons in the arcuate nucleus at 21 weeks of gestation. (D) Area of arcuate nucleus in B at higher magnification showing a population of morphologically developed NPY-positive neurons. (Reproduced from J. Comp. Neurol. with permission from John Wiley & Sons, Inc., 2002).

Neuropeptide Y (NPY) is a peptide that belongs to the pancreatic polypeptide family and is abundant throughout the central and peripheral nervous systems in both human and rat. In the brain, NPY is found at high concentrations in the mesencephalon, medulla, cortex, hippocampus, amygdala, ventral and dorsal striatum, and hypothalamus. As a neuroactive molecule, NPY has been implicated in the regulation of feeding behavior and autonomic and endocrine activity. Particularly instrumental for these ideas was the discovery of NPY-containing networks in the hypothalamus, where this peptide is confined approximately to specific neurons in the arcuate (Fig. 4) and suprachiasmatic nuclei and to fibers and neuronal terminals in the paraventricular and dorsomedial nuclei. Mapping the distribution of NPY in the human brain contributed greatly to the delineations of some functionally significant nuclei and areas. Thus, for example NPY defines the otherwise ambiguous and poorly visible ventral marginal hypothalamic zone, which has been implicated in the regulation of feeding.

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