Distribution of neurotensin/neuromedin N mRNA in rat forebrain: unexpected abundance in hippocampus and subiculum.

Abstract

We have used in situ hybridization to determine the regional distribution of mRNA encoding the neurotensin/neuromedin N (NT/N) precursor in the forebrain of the adult male rat. Cells containing NT/N mRNA are widely distributed in the forebrain. These areas include the septum, bed nucleus of the stria terminalis, preoptic area, hypothalamus, amygdala, accumbens nucleus, caudate-putamen, and piriform and retrosplenial cortex. In general, the regional distribution of NT/N mRNA corresponds to the previously determined distribution of neurotensin-immunoreactive cell bodies; however, several notable exceptions were observed.The most striking difference occurs specifically in the CA1 region of the hippocampus, where intense labeling is associated with the pyramidal cell layer despite the reported absence of neurotensin-immunoreactive cells in this region. Analysis of microdissected tissue by S1 nuclease protection assay confirmed the abundance of authentic NT/N mRNA in CAL. A second major discrepancy between NT/N mRNA abundance and neurotensin-immunoreactivity occurs in the intensely labeled subiculum, a region that contains only scattered neurotensin-immunoreactive cells in the adult. These results suggest that, in specific regions of the forebrain, NT/N precursor is processed to yield products other than neurotensin. In addition, these results provide an anatomical basis for studying the physiological regulation of NT/N mRNA levels in the forebrain.Neurotensin (NT), a tridecapeptide with widespread distribution in the central nervous system and peripheral tissues of mammals, is one of a family of structurally related peptides with members manifesting diverse biological activities (1). The structure of the rat gene encoding NT has recently been determined (2), and the general features of the predicted NT precursor for the rat are the same as those of the predicted precursors for the dog (3) and cow (2). In each species, a precursor protein of 169-170 amino acid residues encodes both NT and neuromedin N, a peptide similar in structure to NT (4). A comparison of the sequences of the complete neurotensin/neuromedin N (NT/N) precursor from rat, dog, and cow reveals a high degree of conservation. This finding is consistent with the idea that the precursor may be processed to yield biologically active peptides that are as yet unknown.There is increasing evidence that NT functions as a neuroregulatory substance in the mammalian central nervous system (1, 5). Effects produced by NT administration in the central nervous system include hypothermia, hypotension, and antinociception. NT has also been implicated in the central regulation of anterior pituitary function (6, 7). NTimmunoreactive cell bodies are most numerous in the forebrain, with widespread distribution in limbic regions such as the septum, preoptic area, hypothalamus, and amygdala (8).Other forebrain regions, such as the dorsal subiculum, contain many NT-immunoreactive cell bodies during early stages of development, but the number of neurons with detectable...

Chronic cocaine increases neurotensin gene expression in the shell of the nucleus accumbens and in discrete regions of the striatum

“…4). This distribution of NT mRNA is in agreement with other studies examining mRNA expression in the rat forebrain [1,8,11,32].…”

Neurotensin Gene Expression and Behavioral Responses Following Administration of Psychostimulants and Antipsychotic Drugs in Dopamine D3 Receptor Deficient Mice

“…The distribution of NT mRNA expression in vehicleinjected mice was restricted rostrally to the nucleus accumbens shell, the olfactory tubercle and the lateral septum (Figure 2), in agreement with studies in the rat (Alexander et al 1989;Merchant and Dorsa 1993;Betancur et al 1997). Labeling in the nucleus accumbens shell was irregular, with intensely labeled cell clusters scattered within the region.…”

Central Administration of the Neurotensin Receptor Antagonist, SR48692, Modulates Diurnal and Stress-Related Hypothalamic-Pituitary-Adrenal Activity

“…The PVN receives a wide array of inputs from NT-expressing cells located within several regions known to modulate HPA activity. Extrahypothalamic nuclei in cluding the central nucleus of the amygdala and the bed nucleus of the stria terminalis are particularly enriched with NT-like immunoreactivity, mRNA and receptors [55][56][57], Within the hypothalamus, areas such as the arcuate, ventromedial and periventricular nuclei, the me dial preoptic area and the anterior and lateral hypothal ami express dense NT-like inimunoreactive staining. These nuclei may have been affected by chronic SR48692 exposure that was primarily targeted towards the PVN.…”