Transplantation of dissociated foetal serotonin neurons into the transected spinal cord of adult rats

Privat, Alain; Mansour, Hussein; Pavy, Allan; Geffard, M.; Sandillon, F.

doi:10.1016/0304-3940(86)90166-7

Cited by 79 publications

(21 citation statements)

References 14 publications

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“…These neurons have the added tendency to sprout after injury, whether caused by direct chemical lesion (Zhou et al, 1995) or spinal cord trauma (Sharma et al, 1990; Inman and Steward, 2003; Camand et al, 2004). When transplanted into the injured adult spinal cord, serotonergic neurons can elongate and incorporate remarkably well into the CNS parenchyma (Privat et al, 1986; Foster et al, 1989; Yakovleff et al, 1995; Feraboli-Lohnherr et al, 1997; Ribotta et al, 2000), where they can bring about a measure of functional recovery. Clearly, there must be some as yet unknown special property within these neurons that allows them to survive so well within inhibitory environments.…”

Section: Introductionmentioning

confidence: 99%

The Unusual Response of Serotonergic Neurons after CNS Injury: Lack of Axonal Dieback and Enhanced Sprouting within the Inhibitory Environment of the Glial Scar

Hawthorne¹,

Hu²,

Kundu³

et al. 2011

J. Neurosci.

100

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Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury. To understand the mechanisms that underlie their unusual properties, we used a combinatorial approach comparing the behavior of serotonergic and cortical axon tips over time in the same injury environment in vivo and to growth-promoting or -inhibitory substrates in vitro. After a thermocoagulatory lesion in the rat frontoparietal cortex, callosal axons become dystrophic and die back. Serotonergic axons, however, persist within the lesion edge. At the third week post-injury, 5-HT+ axons sprout robustly. The lesion environment contains both growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) and growth-promoting laminin. Transgenic mouse serotonergic neurons specifically labeled by enhanced yellow fluorescent protein under control of the Pet-1 promoter/enhancer (ePet-EYFP) or cortical neurons were cultured on low amounts of laminin +/− relatively high concentrations of the CSPG aggrecan. Serotonergic neurons extended considerably longer neurites than did cortical neurons on low laminin and exhibited a remarkably more active growth cone on low laminin plus aggrecan during time-lapse imaging than did cortical neurons. Chondroitinase ABC treatment of laminin/CSPG substrates resulted in significantly longer serotonergic but not cortical neurite lengths. This increased ability of serotonergic neurons to robustly grow on high amounts of CSPG may be partially due to significantly higher amounts of GAP-43 and/or β1 integrin than cortical neurons. Blocking β1 integrin decreased serotonergic and cortical outgrowth on laminin. Determining the mechanism by which serotonergic fibers persist and sprout after lesion could lead to therapeutic strategies for both stroke and spinal cord injury.

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Section: Introductionmentioning

confidence: 99%

The Unusual Response of Serotonergic Neurons after CNS Injury: Lack of Axonal Dieback and Enhanced Sprouting within the Inhibitory Environment of the Glial Scar

Hawthorne¹,

Hu²,

Kundu³

et al. 2011

J. Neurosci.

100

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“…Recently, in the rat, it has been shown that monoaminergic reinnervation of the lumbar spinal cord could be obtained by transplantation of embryonic neurons expressing either serotonin or noradrenaline Privat et al 1986Privat et al , 1988Privat et al , 1989. In rats spinalised as adults, intrinsic serotonergic or noradrenergic neurons are normally absent from the thoraco-lumbar spinal cord and all the descending monoaminergic terminals degenerate within 8 days after the lesion (Haggendal and Dahlstrsom 1973;Magnusson 1973, Yakovleff et al 1989).…”

Section: Introductionmentioning

confidence: 99%

Recovery of locomotor activity in the adult chronic spinal rat after sublesional transplantation of embryonic nervous cells: specific role of serotonergic neurons

et al. 1997

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Locomotor movements are programmed in a specialised neuronal network that is localised in the central nervous system and referred to as the central pattern generator (CPG) for locomotion. This CPG can be activated by pharmacological agents such as monoamines. The aim of the present study was to try to activate the CPGs by using cells that are supposed to release serotonin locally. Adult chronic spinal rats were injected with embryonic brainstem neurons within the spinal cord under a thoracic transection. This procedure resulted in a monoaminergic reinnervation of the lumbar enlargement. With the help of a specific neurotoxin for noradrenergic neurons (6-hydroxydopamine), it was possible to isolate the serotonergic system. After such transplantation of monoaminergic neurons and even with serotonergic neurons alone, a bilateral, alternating, rhythmic locomotor-like activity recovered in hindlimbs. Furthermore, this locomotor-like activity was clearly facilitated when the re-uptake of serotonin was blocked by zimelidine. Therefore, we conclude that transplanted embryonic serotonergic neurons are able to activate the CPG for locomotion.

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“…Other workers [18] have shown that embryonic neurons can tra vel through the white matter and that axons and/or dendrites can grow in this environment [2,6,9,19]. This is an interesting phenomenon, since recent experiments of Schwab and Caroni [20] have shown that myelin in the white matter contains a nonpermissive substrate which can inhibit neuronal attachment and neurite outgrowth.…”

Section: Discussionmentioning

confidence: 95%

“…However, some workers have reported that em bryonic neurons can migrate following grafting; Sotelo and AlvaradoMallart [24] showed that Purkinje cells migrate more than 600 pm in the cerebellum of mutant mice. Privat et al [9] showed that embryonic serotoninergic neurons can migrate approximatively 15 mm from the injection site when these cells were grafted into the adult transected spi nal cord. Recently Sieradzan and Vrbova [11] demonstrated that cells of embryonic spinal cord origin can migrate from the graft into the host's spinal cord over a relatively large distance; these cells can sur vive for several months.…”

Section: Discussionmentioning

confidence: 99%

“…Since then, several types of trans plantation techniques have been used to study spinal cord regenera tion; these include the use of peripheral nerve as a bridge [3], the use of spinal cord of embryonic origin [4][5][6][7], and the use of embryonic brain tissue [8][9][10], Most of these studies have concentrated on the survival and growth of the graft and on the reinnervation of the host spinal cord which had been partially or completely transected. Only Sieradzan and Vrbova [11] have examined the fate of embryonic motoneurons when grafted into the adult rat spinal cord.…”

Section: Introductionmentioning

confidence: 99%

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Grafting of Embryonic Motoneurons into Spinal Cord and Striatum of Adult Mice

Demierre

Ruiz-Flandes²,

Kato³

1990

Stereotact Funct Neurosurg

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The aim of the present work was to determine whether embryonic motoneurons could survive in the adult CNS and whether they display different survival and growth characteristics in their natural site (the spinal cord) as compared to an ectopic site (the striatal region of the brain). Specific labelling of embryonic motoneurons was obtained by retrograde transport of a fluorescent tracer (carbocyanine) followed by partial purification of the dissociated motoneurons on a density gradient. This technique offers the advantage that only the motoneurons in the cell suspension used for the grafts contain the fluorescent tracer. This study demonstrates that these motoneurons can survive and differentiate in the white and grey matters, not only in the adult spinal cord, but also in the brain. Furthermore, these motoneurons can migrate approximately 2 mm in the spinal cord and 4 mm in the brain.

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Transplantation of dissociated foetal serotonin neurons into the transected spinal cord of adult rats

Cited by 79 publications

References 14 publications

The Unusual Response of Serotonergic Neurons after CNS Injury: Lack of Axonal Dieback and Enhanced Sprouting within the Inhibitory Environment of the Glial Scar

The Unusual Response of Serotonergic Neurons after CNS Injury: Lack of Axonal Dieback and Enhanced Sprouting within the Inhibitory Environment of the Glial Scar

Recovery of locomotor activity in the adult chronic spinal rat after sublesional transplantation of embryonic nervous cells: specific role of serotonergic neurons

Grafting of Embryonic Motoneurons into Spinal Cord and Striatum of Adult Mice

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