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Peptidergic projections from the rat paraventricular hypothalamic nucleus to the spinal cord
Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The survival of the organism is dependent on keeping a balanced internal milieu in an ever-changing environment The process to achieve this balance is called homeostasis and it is accomplished by the consonant action of the endocrine system and the autonomic nervous system. Specific parts of the central nervous system (CNS) control these systems in response to various sensory inputs. One of the key sites for the coordinated action of these two homeostasis systems is the paraventricular hypothalamic nucleus (PVH). Tirrough its projections to the pituitary the PVH controls the release of different hormones. In addition, it projects heavily to brain stem and spinal cord autonomic centers. Furthermore, the PVH projects to the superficial layers of the spinal cord, where nerve fibers conveying pain and temperature modalities terminate. Thus, in addition to its motor control of the homeostasis system, the PVH may influence the processing of sensory inputs that are important for homeostatic regulation. The aim of this thesis was to investigate some aspects of the organization and function of the neuronal pathways projecting from the PVH to the spinal cord in the rat.

Vasopressin, which is a peptide that is synthesized by PVH neurons, has been proposed to regulate several different processes in the spinal cord. However, the source of vasopressin fibers within the spinal cord has been a matter of some dispute. Thus, firstly, we investigated the distribution of neurons expressing vasopressin mRNA in the naive rat, thereby providing the first complete screening of the CNS for this neuropeptide at the mRNA level. The results confmn some earlier work, but also demonstrate several new sites of vasopressin mRNA synthesis. Some sites previously thought to produce vasopressin displayed no vasopressin mRNA. Our results show that the PVH is the only putative site of spinally-projecting vasopressin neurons in the naive rat Hence, all functions exerted by vasopressin in the spinal cord are likely to be controlled by the PVH.

Secondly, we examined the neurochemical profile of the PVH neurons that project to the spinal cord. We show that 41% of these neurons express dynorphin mRNA, 20% express enkephalin mRNA, 38% express oxytocin mRNA, and 42% express vasopressin mRNA. This is the first time that dynorphin has been shown in PVH neurons with spinal projections, and the figures for the other peptides are substantially higher than what has been reported in previous shldies. In addition, we demonstrate that each of the spinal cord projecting subdivisions of the PVH displays distinct peptide expression patterns.

Thirdly, we investigated the physiological effect of the PVH on nociceptive transmission in the spinal cord dorsal horn. However, with the present experimental approach we could not show a consistent effect of PVH stimulation on nociceptive neurons in the spinal dorsal horn. The varying results we achieved are ascribed to the functional heterogeneity of the PVH as revealed by our previous studies.

The present data contribute to the nnderstanding of the complex organization of the PVH. The parcellation of peptide-expressing neurons into distinct spinal cord projecting subnuclei is likely to reflect distinct functional roles of these subnuclei, and may provide the anatomical basis for the ability of the PVH to control many different processes in the spinal cord The nnderstanding of the physiological profile of these different subnuclei will provide insight into the control of homeostasis.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2000. , 52 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 627
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25654Local ID: 10030ISBN: 91-7219-584-3 (print)OAI: oai:DiVA.org:liu-25654DiVA: diva2:246202
Public defence
2000-05-12, Berzeliussalen, Hälsouniversitetet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-12-11Bibliographically approved
List of papers
1. Preprovasopressin mRNA is not present in dorsal root ganglia of the rat
Open this publication in new window or tab >>Preprovasopressin mRNA is not present in dorsal root ganglia of the rat
1996 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 209, no 10, 125-128 p.Article in journal (Refereed) Published
Abstract [en]

Immunohistochemical studies on colchic ine-treated rats have suggested that more than half of the neurons in dorsal root ganglia (DRG) contain vasopressin. Thus, vasopressin would be the most commonly found peptide in DRG neurons. In the present study we have reexamined the presence of vasopressin in DRG neurons, using a sensitive in situ hybridization method employing long riboprobes that will detect very small amounts of mRNA. The C3, C6, T2, T12, L2 and L5 DRG were studied. None of these ganglia contained any preprovasopressin mRNA. Yet, dense labeling for preprovasopressin mRNA was seen on simultaneously processed hypothalamic sections and a heavy preprotachykinin mRNA expression was seen in adjacent DRG sections. These findings demonstrate that vasopressin is not produced in DRG in normal rats.

Keyword
Vasopressin, In situ hybridization, Tachykinin, Spinal cord
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79557 (URN)10.1016/0304-3940(96)12616-1 (DOI)
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2017-12-07Bibliographically approved
2. Distribution of preprovasopressin mRNA in the rat central nervous system
Open this publication in new window or tab >>Distribution of preprovasopressin mRNA in the rat central nervous system
1999 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 411, no 2, 181-200 p.Article in journal (Refereed) Published
Abstract [en]

Vasopressin released in the central nervous system has been shown to be involved both in homeostatic mechanisms (e.g., water balance, thermoregulation, cardiovascular regulation, metabolism, and antinociception) and in higher brain functions (e.g., social recognition and communication, and learning and memory). Many nuclear groups have been proposed to synthesize vasopressin, but available data are conflicting. We have used a sensitive in situ hybridization technique to identify the distribution of the neurons that may be the origin of the vasopressin in the central nervous system of the male Sprague-Dawley rat. Vasopressin mRNA-expressing neurons were most abundant in the hypothalamus (e.g., the paraventricular, supraoptic, and suprachiasmatic nuclei) but were also seen in the medial amygdaloid nucleus, the bed nucleus of stria terminalis, and the nucleus of the horizontal diagonal band. Previously unreported vasopressinergic neurons were seen in the entorhinal and piriform cortices, the ventral lateral portion of the parabrachial nucleus, the pedunculopontine nucleus, and the rostral part of the ventral periaqueductal gray matter and the adjacent portion of the mesencephalic reticular nucleus. Vasopressin mRNA expression suggestive of neuronal labeling was seen in the pyramidal layer of the CA1–3 fields and the dentate gyrus of the hippocampus. In addition, vasopressin mRNA expression, probably representing axonal mRNA, was detected over the hypothalamopituitary tract. No or insignificant preprovasopressin mRNA expression was present in the cerebellum, locus coeruleus, subcoeruleus, or the spinal cord. These findings provide novel information on the distribution of vasopressin neurons that are important for our understanding of how vasopressin acts in the brain.

Keyword
paraventricular hypothalamus, entorhinal cortex, hippocampus, parabrachial nucleus, periaqueductal gray matter, axonal mRNA
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24941 (URN)10.1002/(SICI)1096-9861(19990823)411:2<181::AID-CNE2>3.0.CO;2-1 (DOI)9349 (Local ID)9349 (Archive number)9349 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
3. Spinal cord-projecting vasopressinergic neurons in the rat paraventricular hypothalamus
Open this publication in new window or tab >>Spinal cord-projecting vasopressinergic neurons in the rat paraventricular hypothalamus
1999 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 411, no 2, 201-211 p.Article in journal (Refereed) Published
Abstract [en]

The paraventricular hypothalamic nucleus (PVH) is a key structure for the maintenance of homeostasis. Homeostatic regulation includes modulation of signaling in the spinal cord. This may be exerted by neurons in the PVH with spinal projections. However, the PVH is not a homogeneous structure, but consists of anatomically and functionally distinct subdivisions. In this study, we have analyzed the distribution of spinal cord-projecting PVH neurons that express vasopressin, an important neuropeptide in autonomic regulation. Vasopressinergic neurons were identified with a radiolabeled riboprobe complementary to vasopressin mRNA combined with immunohistochemical labeling of retrogradely transported cholera toxin subunit b in spinally projecting neurons. More than 40% of the spinally projecting neurons in the PVH of naive Sprague-Dawley rats were found to express vasopressin mRNA. The lateral parvocellular subdivision and the ventral part of the medial parvocellular subdivision contained the densest distribution of spinal cord-projecting vasopressin mRNA-expressing neurons. The magnocellular subdivisions displayed large numbers of vasopressin mRNA-expressing neurons, but very few of those projected to the spinal cord. The dorsal parvocellular subdivision contained a large number of spinally projecting neurons, but very few of those expressed vasopressin mRNA. These findings show that the PVH gives rise to a major vasopressinergic projection to the spinal cord and that the spinal cord-projecting vasopressinergic neurons are parceled into anatomically distinct cell groups. This provides an anatomical basis for a selective activation of functionally different groups in the PVH as part of a behaviorally adaptive response, including modulation of autonomic activity and pain processing at the spinal level.

Keyword
in situ hybridization, retrograde labeling, subnuclei, parvocellular, mRNA
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24950 (URN)10.1002/(SICI)1096-9861(19990823)411:2<201::AID-CNE3>3.0.CO;2-3 (DOI)9360 (Local ID)9360 (Archive number)9360 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
4. Dynorphin mRNA-expressing neurons in the rat paraventricular hypothalamic nucleus project to the spinal cord
Open this publication in new window or tab >>Dynorphin mRNA-expressing neurons in the rat paraventricular hypothalamic nucleus project to the spinal cord
2000 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 285, no 3, 161-164 p.Article in journal (Refereed) Published
Abstract [en]

The opioid peptide dynorphin is important for the regulation of neuronal activity in the spinal cord. Because dynorphin is produced by neurons throughout the neuraxis, there are many putative sources for spinal dynorphin fibers, in addition to those originating from spinal cord neurons. Using a sensitive double-labeling technique combining in situ hybridization and tract tracing, the present study demonstrates that the paraventricular hypothalamic nucleus (PVH) of adult naı̈ve male Sprague–Dawley rats contains large numbers of dynorphin mRNA-producing cells with projections to the spinal cord. Thus, more than 40% of the spinally projecting neurons in PVH were found to express dynorphin mRNA. This novel finding suggests that the PVH is a major source of spinal dynorphin that may be of importance for the processing of pain and visceral information.

Keyword
Preprodynorphin, Paraventricular hypothalamic nucleus, In situ hybridization, Retrograde labeling, Parvocellular, Descending
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25043 (URN)10.1016/S0304-3940(00)01093-4 (DOI)9469 (Local ID)9469 (Archive number)9469 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
5. Neuropeptide expression in rat paraventricular hypothalamic neurons that project to the spinal cord
Open this publication in new window or tab >>Neuropeptide expression in rat paraventricular hypothalamic neurons that project to the spinal cord
2001 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 433, no 2, 222-238 p.Article in journal (Refereed) Published
Abstract [en]

The paraventricular hypothalamic nucleus (PVH) exerts many of its regulatory functions through projections to spinal cord neurons that control autonomic and sensory functions. By using in situ hybridization histochemistry in combination with retrograde tract tracing, we analyzed the peptide expression among neurons in the rat PVH that send axons to the spinal cord. Projection neurons were labeled by immunohistochemical detection of retrogradely transported cholera toxin subunit B, and radiolabeled long riboprobes were used to identify neurons containing dynorphin, enkephalin, or oxytocin mRNA. Of the spinally projecting neurons in the PVH, approximately 40% expressed dynorphin mRNA, 40% expressed oxytocin mRNA, and 20% expressed enkephalin mRNA. Taken together with our previous findings on the distribution of vasopressin-expressing neurons in the PVH (Hallbeck and Blomqvist [1999] J. Comp. Neurol. 411:201–211), the results demonstrated that the different PVH subdivisions display distinct peptide expression patterns among the spinal cord–projecting neurons. Thus, the lateral parvocellular subdivision contained large numbers of spinal cord–projecting neurons that express any of the four investigated peptides, whereas the ventral part of the medial parvocellular subdivision displayed a strong preponderance for dynorphin- and vasopressin-expressing cells. The dorsal parvocellular subdivision almost exclusively contained dynorphin- and oxytocin-expressing spinal cord–projecting neurons. This parcellation of the peptide-expressing neurons suggested a functional diversity among the spinal cord–projecting subdivisions of the PVH that provide an anatomic basis for its various and distinct influences on autonomic and sensory processing at the spinal level.

Keyword
dynorphin, enkephalin, oxytocin, vasopressin, mRNA, in situ hybridization, retrograde labeling, parvocellular
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24946 (URN)10.1002/cne.1137 (DOI)9355 (Local ID)9355 (Archive number)9355 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
6. Effect of Stimulation of the Paraventricular Hypothalamic Nucleus on Noxious-Evoked Fos-immunoreactlvity In the Rat lumbar Spinal Cord
Open this publication in new window or tab >>Effect of Stimulation of the Paraventricular Hypothalamic Nucleus on Noxious-Evoked Fos-immunoreactlvity In the Rat lumbar Spinal Cord
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The paraventricular nucleus of the hypothalamus (PVH) provides a prominent descending projection to the superficial dorsal horn, and contains a number of neuropeptides that are know to influence nociceptive processing. In the present study, we injected formalin subcutaneously into the hind paws of unanesthetized rats and studied the noxious-evoked Fos protein expression in the dorsal horn following simultaneous unilateral injection of the glutamate receptor agonist kainic acid into the PVH. Although some cases displayed less Fos-inununoreactivity in the lumbar spinal cord on the side ipsilateral to the PVH activation than on the contralateral side, others displayed no side differences, and one case showed more labeling in the ipsilateral dorsal horn than on the contralateral side, Because different parts of the PVH were activated in the different experiments, the present observations suggest that the different peptide expressing populations of spinal cordprojecting neurons in PVH may have different, and perhaps opposing functions in the spinal dorsal horn.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79560 (URN)
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2012-08-08Bibliographically approved

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