Neurotensin immunoreactivity in the human cingulate gyrus, hippocampal subiculum and mammillary bodies. Its potential role in memory processing

Sakamoto, Noboru; Michel, Jean-Philippe; Kiyama, Hiroshi; Tohyama, Masaya; Kopp, Nicolas; Pearson, John

doi:10.1016/0006-8993(86)90756-0

Cited by 46 publications

(11 citation statements)

References 16 publications

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“…In the dorsal subiculum of the rat, the number of cell bodies with detectable NT-like immunoreactivity reaches a maximum during the first postnatal week (9) and then decreases markedly by adulthood, so that only scattered cells are visible (9,15,16). There are indications of a similar reduction in NT-immunoreactive cells during development of the human subiculum (31). Parallel changes occur in the density of NT-immunoreactive fibers in the mammillary body, and a NT-immunoreactive pathway from subiculum to mammillary body has been identified in the neonatal rat (17) and human neonate (31).…”

Section: Discussionmentioning

confidence: 61%

“…There are indications of a similar reduction in NT-immunoreactive cells during development of the human subiculum (31). Parallel changes occur in the density of NT-immunoreactive fibers in the mammillary body, and a NT-immunoreactive pathway from subiculum to mammillary body has been identified in the neonatal rat (17) and human neonate (31). A NT-immunoreactive pathway from dorsal subiculum to anterior cingulate cortex in the adult rat has also been reported (16).…”

Section: Discussionmentioning

confidence: 64%

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

Alexander

Miller

Dorsa

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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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...

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 64%

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

Alexander

Miller

Dorsa

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…This could suggest that NT may have a role in the integration of higher brain functions and emotions. Already, a potential role for NT in memory processing has been pro osed (Sakamoto et al, 1986). Also, the high gray matter may suggest a role for this neuropeptide in the modulation of nociceptive functions (Nemeroff et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

Neurotensin receptor binding sites in monkey and human brain: Autoradiographic distribution and effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine treatment

Quirion

Welner

Gauthier

et al. 1987

Synapse

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Neurotensin (NT) receptor binding sites were characterized and localized by using membrane binding assay and in vitro receptor autoradiography in monkey and human brain. Additionally, the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment on NT binding sites were investigated in monkey. [125I]Tyr3-NT ([125I]NT) apparently binds to a single class of high-affinity sites (Kd in nanomolar range) in both species. Ligand selectivity patterns strongly suggest that the structural requirements of both monkey and human brain NT receptors are very similar to those previously reported in other tissues, such as those of the rat brain and rat stomach. In monkey brain, [125I]NT binding sites are discretely distributed with high densities of sites found in the cingulate cortex, amygdala, hippocampus, ventral tegmental area, substantia nigra, and periaqueductal gray matter. A similar pattern is observed in the human brain. However, the laminar distribution of [125]NT binding sites in cortex varies between monkey and human brain. In monkey brain, [125I]NT binding sites are mostly concentrated in deep cortical layers while the laminar distribution of NT sites changes with cortical areas in human brain. The densities of [125I]NT binding sites are markedly decreased in the caudate, putamen, and substantia nigra in MPTP-treated monkeys. These results suggest strong interactions between NT and dopaminergic systems in both monkey and human brain tissues.

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“…First, the NT-containing cell bodies are observed in the EC (Atoji et al, 1995) which innervates the dentate gyrus. Second, a very large population of the molecular layer of the dentate gyrus where the PP-GC synapses form contains numerous NT-immunoreactive varicose axons (Sakamoto et al, 1986). Third, the dentate gyrus exhibits a high density of binding sites for NT (Cadet et al, 1993; Kohler et al, 1987; Moyse et al, 1987; Rowe et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Neurotensinergic augmentation of glutamate release at the perforant path-granule cell synapse in rat dentate gyrus: Roles of L-Type Ca2+ channels, calmodulin and myosin light-chain kinase

2015

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Neurotensin (NT) serves as a neuromodulator in the brain where it is involved in modulating a variety of physiological functions including nociception, temperature, blood pressure and cognition, and many neurological diseases such as Alzheimer’s disease, schizophrenia and Parkinson’s disease. Whereas there is compelling evidence demonstrating that NT facilitates cognitive processes, the underlying cellular and molecular mechanisms have not been fully determined. Because the dentate gyrus expresses high densities of NT and NT receptors, we examined the effects of NT on the synaptic transmission at the synapse formed between the perforant path (PP) and granule cells (GC) in the rats. Our results demonstrate that NT persistently increased the amplitude of the AMPA receptor-mediated EPSCs at the PP-GC synapse. NT-induced increases in AMPA EPSCs were mediated by presynaptic NTS1 receptors. NT reduced the coefficient of variation and paired-pulse ratio of AMPA EPSCs suggesting that NT facilitates presynaptic glutamate release. NT increased the release probability and the number of readily releasable vesicles with no effects on the rate of recovery from vesicle depletion. NT-mediated augmentation of glutamate release required the influx of Ca2+ via L-type Ca2+ channels and the functions of calmodulin and myosin light chain kinase. Our results provide a cellular and molecular mechanism to explain the roles of NT in the hippocampus.

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Neurotensin immunoreactivity in the human cingulate gyrus, hippocampal subiculum and mammillary bodies. Its potential role in memory processing

Cited by 46 publications

References 16 publications

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

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

Neurotensin receptor binding sites in monkey and human brain: Autoradiographic distribution and effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine treatment

Neurotensinergic augmentation of glutamate release at the perforant path-granule cell synapse in rat dentate gyrus: Roles of L-Type Ca2+ channels, calmodulin and myosin light-chain kinase

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