You have to constantly train your eyes and constantly motivate yourself to respect that individuality. ( I) A very weak signal for the GalR1 transcript is seen in the LC, but it is probably not present in the NA neurons.Shipping Department holiday schedule is from Dec 24/14 until Jan 5/15 Please note that any book or subscription orders placed between Dec 24/14 and Jan 05/15 will not be processed or shipped until Jan 06/15 Classifications Search by Keywords: List by Classifications: List by Author: Articles The Individuality of the Natural Tooth Article Date: Vol 6, No 5 Every patient is different. Note bluish autofluorescence from pigment in NA-LC neurons (arrowheads in H). Strong signal for GalR3 is seen in LC ( G) but not after hybridization with the control probe ( H).
Insets A′, C′, and E′ show results after hybridization with sense/control probe. Note the variability in the strength of the signal for galanin mRNA. The three markers TH ( A and B), galanin ( C and D), and GalR3 ( E and F) show an overlapping distribution pattern, whereby TH and GalR3 transcript levels are similar in all cells. Autofluorescent pigmented neurons are indicated by arrowheads, and positive cells are indicated by arrows. Dark-field ISH photomicrographs showing the distribution of galanin, GalR1, GalR3, and nNOS in the LC. This group is localized in the midline ventral to the aqueduct, extending laterally in two wings in the ventral PAG (vPAG) and continuing further ventrally as MRN with many neurons dispersed in the pontine reticular formation (). In contrast, the 5-HT neurons expressing the TPH2 transcript in the caudal mesencephalon/pons ( and ) extend over a long distance with characteristic distribution patterns at different levels (). Therefore, in several instances we used the pigment as a marker for NA-LC neurons instead of using TH ISH. In the dark-field configuration the NA neurons can be distinguished by their autofluorescence (). This nucleus is characterized by the expression of the catecholamine-synthesizing enzyme TH, here visualized through the TH transcript ( and ). The LC/subcoeruleus is a bilateral compact accumulation of neurons in the pons with a limited rostro-caudal extension and a characteristic localization close to the fourth ventricle. Such knowledge may be important when considering therapeutic principles and drug development.
For example, GalR3 seems to be the important galanin receptor in both the human LC and DRN versus GalR1 and -2 in the rodent brain. These findings show distinct differences between the human brain and rodents, especially rat, in the distribution of the galanin system and some other transmitter systems. Nitric oxide synthase was not detected in serotonin neurons. VGLUT2 transcripts were found in very small, nonpigmented cells in the LC and in the lateral and dorsal aspects of the periaqueductal central gray. VGLUT1 and -2 were strongly expressed in the pontine nuclei but could not be detected in LC or serotonin neurons. In forebrain regions the ranking was GalR1 >galanin >GalR2.
The qPCR analysis at the LC level ranked the transcripts in the following order in the LC: galanin >GalR3 >GalR1 >GalR2 in the DRN the ranking was galanin >GalR3 >GalR1 = GalR2. Galanin and GalR3 mRNA were found in many noradrenergic LC neurons, and GalR3 overlapped with serotonin neurons in the DRN.
Quantitative real-time PCR (qPCR) was used also. Using riboprobe in situ hybridization, we studied the localization of the transcripts for the neuropeptide galanin and its receptors (GalR1–R3), tryptophan hydroxylase 2, tyrosine hydroxylase, and nitric oxide synthase as well as the three vesicular glutamate transporters (VGLUT 1–3) in the locus coeruleus (LC) and the dorsal raphe nucleus (DRN) regions of postmortem human brains. The results show some distinct species differences between human and rodent noradrenergic and serotonergic neurons which may better inform the development of novel anxiolytic/antidepressant drugs. In this study we selected chemical markers associated with central noradrenaline and serotonin neurons, key systems in research on and current treatment of depression, and studied their expression with in situ hybridization in postmortem human brains. Such data often have been the basis in the search for new drugs. For decades rodents have been used to explore normal brain functions and mechanisms underlying brain diseases.
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