Cross-species transplantation of the suprachiasmatic nuclei from rats to siberian chipmunks (Eutamias sibiricus) with suprachiasmatic lesions

doi:10.1016/0304-3940(91)90162-M

Neuroscience Letters

Volume 123, Issue 1, 11 February 1991, Pages 77-81

https://doi.org/10.1016/0304-3940(91)90162-M Get rights and content

Abstract

Suprachiasmatic nuclei (SCN) obtained from neonatal or embryonic 19 or 20 day rats, were grafted into the third ventricle of SCN-lesioned arrhythmic siberian chipmunks. Four out of 37 chipmunks showed reappearance of circadian rhythmicity in wheel running activity. In all 4 cases, at least one surviving graft was confirmed in the host brain. Also, vasopressin and vasoactive intestinal polypeptide (VIP)-like immunoreactive substances were found in the graft, suggesting the existence of live SCN neurons. Although the number of successful cases and the intensity of the restored rhythm was limited compared to the intra-species grafting in rats, a possibility that cross-species transplantation of SCN can restore circadian rhythmicity was shown.

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Cited by (23)

Resilience in the suprachiasmatic nucleus: Implications for aging and Alzheimer's disease
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Citation Excerpt :
From there, the tissue would graft itself onto the inner walls of the third ventricle or within the interventricular foramina (Foramen of Monro, conduits within the ventricular system that connect the third ventricle with each of the two lateral ventricles). After securely attaching to the host ventricle, the homograft (or xenograft) followed a developmental trajectory that was only crudely similar to the developmental course it would have followed in residence within the original donor brain (Saitoh et al., 1991; Sollars et al., 1995). As often was the case for successful transplants, this meant that overlapping clusters of VIP and AVP-immunopositive cells would segregate to the ventrolateral and dorsomedial portions of the graft, respectively (Griffioen et al., 1993; Wiegand and Gash, 1988; Boer and Griffioen, 1990; DeCoursey and Buggy, 1989).
Many believe that the circadian impairments associated with aging and Alzheimer's disease are, simply enough, a byproduct of tissue degeneration within the central pacemaker, the suprachiasmatic nucleus (SCN). However, the findings that have accumulated to date examining the SCNs obtained postmortem from the brains of older individuals, or those diagnosed with Alzheimer's disease upon autopsy, suggest only limited atrophy. We review this literature as well as a complementary one concerning fetal-donor SCN transplant, which established that many circadian timekeeping functions can be maintained with rudimentary (structurally limited) representations of the SCN. Together, these corpora of data suggest that the SCN is a resilient brain region that cannot be directly (or solely) implicated in the behavioral manifestations of circadian disorganization often witnessed during aging as well as early and late progression of Alzheimer's disease. We complete our review by suggesting future directions of research that may bridge this conceptual divide and briefly discuss the implications of it for improving health outcomes in later adulthood.
The suprachiasmatic nucleus and the circadian time-keeping system revisited
2000, Brain Research Reviews
Many physiological and behavioral processes show circadian rhythms which are generated by an internal time-keeping system, the biological clock. In rodents, evidence from a variety of studies has shown the suprachiasmatic nucleus (SCN) to be the site of the master pacemaker controlling circadian rhythms. The clock of the SCN oscillates with a near 24-h period but is entrained to solar day/night rhythm by light. Much progress has been made recently in understanding the mechanisms of the circadian system of the SCN, its inputs for entrainment and its outputs for transfer of the rhythm to the rest of the brain. The present review summarizes these new developments concerning the properties of the SCN and the mechanisms of circadian time-keeping. First, we will summarize data concerning the anatomical and physiological organization of the SCN, including the roles of SCN neuropeptide/neurotransmitter systems, and our current knowledge of SCN input and output pathways. Second, we will discuss SCN transplantation studies and how they have contributed to knowledge of the intrinsic properties of the SCN, communication between the SCN and its targets, and age-related changes in the circadian system. Third, recent findings concerning the genes and molecules involved in the intrinsic pacemaker mechanisms of insect and mammalian clocks will be reviewed. Finally, we will discuss exciting new possibilities concerning the use of viral vector-mediated gene transfer as an approach to investigate mechanisms of circadian time-keeping.
Ontogeny of neurotrophin receptor TrkC expression in the rat forebrain and anterior hypothalamus with emphasis on the suprachiasmatic nucleus
1999, Neuroscience
There is little information about neurotrophic regulation in the developing rat hypothalamus. In the present study, we therefore examined the expression of neurotrophin receptor TrkC in the developing forebrain and hypothalamus. In situ hybridization of coronal sections revealed that on the 15th day of gestation, trkC messenger RNA expression is homogeneously distributed over the neocortex, septum, thalamus, hypothalamus, hippocampus, rhinencephalon and the amygdala. Exceptions were the anteroventral nucleus of the hypothalamus and the striatum, which showed higher levels of trkC messenger RNA expression, and the germinal zones which were devoid of trkC messenger RNA. After birth, the homogeneous staining pattern changes into a heterogeneous staining pattern like that found in adulthood. TrkC expression is observed in the area of the suprachiasmatic nucleus as early as E17 and continues until adulthood.
The presence of the TrkC receptor in the E17 suprachiasmatic nucleus suggests that neurotrophin-3 plays a role in development of this structure and that application of neurotrophin-3 could stimulate neuronal survival and neuritic outgrowth in a suprachiasmatic nucleus transplantation model.
Voluntary wheel running: A review and novel interpretation
1998, Animal Behaviour
Voluntary wheel running by animals is an activity that has been observed and recorded in great detail for almost a century. This review shows that it is performed, often with startling intensity and coordination, by a wide variety of wild, laboratory and domestic species with diverse evolutionary histories. However, despite the plethora of published studies on wheel running, there is considerable disagreement between many findings, thus leading to a lack of consensus on explanations of the causality and function. In the initial part of this review, I discuss the internal and external factors that may be involved in the causality of this behaviour, with an emphasis on disparities in both the factual and theoretical development of the subject. I then address the various proposed functions of wheel running, again highlighting evidence to the contrary. This leads to the conclusion that any single theory on the basis of wheel running is likely to be simplistic with little generality. I then present a novel, behaviour-based interpretation in which it is argued that wheel running has no directly analogous naturally occurring behaviour, it is (sometimes) performed for its own sake per se rather than as a redirected or substitute activity, and studies on motivation show that wheel running is self-reinforcing and perceived by animals as ‘important’. This review proposes that wheel running may be an artefact of captive environments or of the running-wheel itself, possibly resulting from feedback dysfunction. I also discuss the ubiquity and intensity of its performance, along with its great plasticity and maladaptiveness, all indicating that if it is an artefact, it is nevertheless one of great interest to behavioural science.
Neural grafting as a tool for the study and reversal of neurobehavioral birth defects
1996, Pharmacology Biochemistry and Behavior
The transplantation of fetal neurons has gained notoriety in recent years for its perceived potential to reverse neurological deficits caused by loss of one or another neuronal population. The present paper describes a neural grafting approach employed by our laboratory to gain more insight into the drug-induced neurobehavioral teratogenicity. Mice were exposed prenatally to phenobarbital by feeding the barbiturate to the pregnant dam on gestation days 9–18. Heroin exposure was accomplished by injecting dams during the same gestational period. At maturity, the drug-exposed offspring displayed profound deficits in specific behavioral tasks, suggesting alterations in the septohippocampal cholinergic pathway. Biochemically, we observed increased presynaptic activity in the pathway, which was not accompanied by a corresponding reduction in postsynaptic activity. Rather, there was a general hyperactivation along the different postsynaptic phases. In contrast, we noted a desensitization of protein kinase C activity in response to the exposure of a cholinergic agonist to the drug-exposed offspring. Subsequent transplantation of embryonic cholinergic cells from normal mice to the impaired hippocampus reversed the behavioral deficits, whereas sham-operated controls exhibited no improvement. Concomitantly, all the biochemical alterations studied, both presynaptic and postsynaptic, were either partially or completely reversed following grafting.
Vasoactive intestinal peptide efferent projections of the suprachiasmatic nucleus in anterior hypothalamic transplants: Correlation with functional restoration of circadian behavior
1995, Experimental Neurology
Circadian rhythmicity can be restored by transplantation of fetal anterior hypothalamic (AH) tissue containing the suprachiasmatic nucleus (SCN) into hosts rendered arrhythmic by SCN ablation. However, the nature of the SCN effector pathways mediating functional recovery has remained elusive. To examine implant-derived SCN innervation of the host, AH homografts (hamster-to-hamster) and heterografts (mouse- or rat-to-hamster) were employed and the distribution of vasoactive intestinal peptide (VIP) within the SCN terminal fields was evaluated. A comparison was made between cases where circadian locomotor activity was restored and cases where circadian rhythmicity remained disrupted following AH transplantation. A dense aggregation of VIP neurons and processes was identified in each transplant that restored behavioral rhythmicity in the host. In these cases, SCN-derived VIP fibers were integrated with the host brain and could be identified in host terminal fields typically innervated by SCN-VIP fibers. A correlation was noted between VIP innervation of the host paraventricular thalamic nucleus (PVT) and restoration of circadian rhythmicity. Neither qualitative nor quantitative differences in transplant VIP projections were noted between AH homografts and heterografts. These results demonstrate that SCN VIP neurons in AH transplants send an appropriately restricted set of efferent projections to the host brain and suggest that SCN efferent projections to the PVT may participate in mediating the functional recovery of circadian locomotor activity.

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^☆: These results were partially presented at the 13th Annual Meeting of the Japan Neuroscience Society, Oct. 4, 1989, Niigata, Japan [9].

^∗∗: Present address: Department of Neurosurgery, Osaka University Medical School, Kita-ku, Osaka 530, Japan.

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Neuroscience Letters

Abstract

References (13)

Fetal suprachiasmatic nucleus transplants: diurnal rhythm recovery of lesioned rats

Brain Res.

Cross-species transplantation of the suprachiasmatic nucleus

Neurosci. Res. Suppl.

Location of the suprachiasmatic nucleus grafts in rats which restored circadian rhythmicity after transplantation

Neurosci. Lett.

Circadian rhythms in multiple unit activity inside and outside the suprachiasmatic nucleus in the diurnal chipmunk (Eutamias sibiricus)

Neurosci. Res.

Transplantation of the neonatal suprachiasmatic nuclei into rats with complete bilateral suprachiasmatic lesions

Neurosci. Res.

Persistence of circadian rhythmicity in a mammalian hypothalamic ‘island’ containing the suprachiasmatic nucleus

Cited by (23)

Resilience in the suprachiasmatic nucleus: Implications for aging and Alzheimer's disease

The suprachiasmatic nucleus and the circadian time-keeping system revisited

Ontogeny of neurotrophin receptor TrkC expression in the rat forebrain and anterior hypothalamus with emphasis on the suprachiasmatic nucleus

Voluntary wheel running: A review and novel interpretation

Neural grafting as a tool for the study and reversal of neurobehavioral birth defects

Vasoactive intestinal peptide efferent projections of the suprachiasmatic nucleus in anterior hypothalamic transplants: Correlation with functional restoration of circadian behavior

Cross-species transplantation of the suprachiasmatic nuclei from rats to siberian chipmunks (Eutamias sibiricus) with suprachiasmatic lesions☆

Abstract

Brain Res.

Neurosci. Res. Suppl.

Neurosci. Lett.

Neurosci. Res.

Neurosci. Res.

Persistence of circadian rhythmicity in a mammalian hypothalamic ‘island’ containing the suprachiasmatic nucleus