Early postnatal administration of 5,7-DHT: Effects on serotonergic neurons and terminals

Towle, Andrew C.; Breese, G.; Mueller, Robert A.; Coyle, Sallyeana; Lauder, Jean M.

doi:10.1016/0006-8993(84)90010-6

Cited by 72 publications

(28 citation statements)

References 25 publications

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“…At 8-12 weeks after intracerebroventricular and intracerebral injection of a specific neurotoxin, 5,, the forebrain regions in adult rats receive varying densities of regenerating serotonergic fibers (Björklund and Stenevi 1979;Jacobs and Azmitia 1992;Ueda and Kawata 1994). In contrast, neonatal intracisternal 5,7-DHT injection induces long-lasting serotonin depletion without evidence of regeneration in regions of the forebrain, including the hippocampal formation (Towle et al 1984;Volpe et al 1992;Pranzatelli and Martens 1992;Ueda et al 2005).…”

Section: Introductionmentioning

confidence: 91%

Regeneration of 5-HT fibers in hippocampal heterotopia of methylazoxymethanol-induced micrencephalic rats after neonatal 5,7-DHT injection

et al. 2009

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In order to elucidate the regeneration properties of serotonergic fibers in the hippocampus of methylazoxymethanol acetate (MAM)-induced micrencephalic rats (MAM rats), we examined serotonergic regeneration in the hippocampus following neonatal intracisternal 5,7-dihydroxytryptamine (5,7-DHT) injection. Prenatal exposure to MAM resulted in the formation of hippocampal heterotopia in the dorsal hippocampus. Immunohistochemical and neurochemical analyses revealed hyperinnervation of serotonergic fibers in the hippocampus of MAM rats. After neonatal 5,7-DHT injection, most serotonergic fibers in the hippocampus of 2-week-old MAM rats had degenerated, while a small number of serotonergic fibers in the stratum lacunosum-moleculare (SLM) of the hippocampus and in the hilus adjacent to the granular cell layer of the dentate gyrus (DG) had not. Regenerating serotonergic fibers from the SLM first extended terminals into the hippocampal heterotopia, then fibers from the hilus reinnervated the DG and some fibers extended to the heterotopia. These findings suggest that the hippocampal heterotopia exerts trophic target effects for regenerating serotonergic fibers in the developmental period in micrencephalic rats.

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Section: Introductionmentioning

confidence: 91%

Regeneration of 5-HT fibers in hippocampal heterotopia of methylazoxymethanol-induced micrencephalic rats after neonatal 5,7-DHT injection

et al. 2009

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“…In previous investigations we have demonstrated the permanent depletion of serotonin (>90%) throughout the adult brain following neonatal 5,7-DHT treatment 35 . In this study we have measured the depletion of substance P and TRH in order to determine biochemically the extent of peptide-serotonin co-localization throughout the brain.…”

Section: Biochemistrymentioning

confidence: 77%

“…In a previous paper we have characterized the extensive destruction of brain serotonergic neurons, following early neonatal 5,7-DHT treatment 35 . Such treatment results in the cell death of more than 85% of serotonergic neurons, yet catecholamine neurons remain undamaged.…”

Section: Discussionmentioning

confidence: 99%

“…In recent reports 6,35 we have demonstrated that 5,7-DHT treatment of neonatal rats leads to permanent destruction of virtually the entire serotonergic neuronal population. Intracisternal injection of 5,7-DHT into 3-day-old rats leads to the rapid degeneration of 80-98% of serotonergic neurons throughout the brain Pretreatment with desipramine or pargyline effectively protects catecholamine neurons from toxic effects of 5,7-DHT In contrast, previous paradigms for 5,7-DHT-induced lesion of serotonergic neurons have been only partially effective, since treatment of adult rats leads to pruning of distal terminals without any apparent proximal damage and loss of cell bodies In this investigation, we applied our technique for the total destruction of the serotonergic system to determine whether or not cells containing the putative co-localized peptides TRH and SP are lesioned concurrently and further, to assess the relative contribution of the co-localized peptide to the total content throughout the brain…”

Section: Introductionmentioning

confidence: 88%

“…1. Following the neonatal treatment, the number of serotonergic neurons and terminals is dramatically reduced throughout the entire brain 35 .…”

Section: Immunocytochemistrymentioning

confidence: 99%

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Early postnatal administration of 5,7-dihydroxytryptamine: Effects on substance P and thyrotropin-releasing hormone neurons and terminals in rat brain

et al. 1986

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Substance P, thyrotropin-releasing hormone (TRH) and serotonin are putative neurotransmitters which have been proposed to coexist in some brain neurons Our previous immunocytochemical and biochemical studies have demonstrated that 85-100% of all serotonin neurons are destroyed following neonatal 5,7-dihydroxtryptamine (5,7-DHT) treatment In this study, we have determined the effect of neonatal 5,7-DHT and desipramine (DMI) treatment on the biochemical content and immunocytochemical localization of substance P and TRH throughout the brain Interestingly, we have observed that virtually all substance P-and TRH-immunoreactive cells in the ventral pons-medulla are destroyed by the neurotoxin. However, peptide-containing neurons in other regions were not affected Additionally, we measured the peptide content and found that TRH is significantly decreased in the spinal cord (−50%) and pons-medulla (−20%), but not in other brain regions Substance P content was not significantly altered in any region, even after a greater than 90% reduction of serotonin These data indicate that the co-localized substance P and TRH forms a small proportion of the total peptide in brain Correspondence A Towle,

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Perinatal supplementation of low doses of ethanol enhances 5-HT restoration in the central nervous system

et al. 1999

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It has been reported that long-term administration of ethanol has deleterious effects on the central nervous system; the alterations are particularly evident if the exposure occurs during development. Our study shows that rat perinatal administration of 3% and 6% ethanol does not alter development of serotonin (5-HT) pathways in the central nervous system, while their reactive changes triggered by neonatal lesioning are greatly altered. The administration of 5, 7-dihydroxytriptamine (5,7-DHT) within 6 hours from birth causes 5-HT fiber degeneration throughout the central nervous system. The loss of 5-HT is particularly relevant in lumbar spinal cord, occipital cortex, and hippocampus. This early decrease in 5-HT content is followed by a slow and partial recovery. If animals are exposed to 3% ethanol during the perinatal period, there is an enhancement of the 5,7-DHT-induced degeneration that is, however, followed by a faster and greater recovery throughout the central nervous system. Conversely, perinatal exposure to 6% ethanol and 5, 7-DHT administration lead to an irreversible 5-HT loss with no subsequent recovery. The deleterious effects of 6% ethanol are accompanied by a reduced expression of neurotrophin. Thus, our study suggests that chronic exposure to ethanol can influence central nervous system plasticity during development. Low doses may enhance neuronal plasticity and repair perhaps via an increased efficacy of neurotrophic factors, whereas higher doses may negatively affect neural development also by means of the impairment of the expression of neurotrophic factors.

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Early postnatal administration of 5,7-DHT: Effects on serotonergic neurons and terminals

Cited by 72 publications

References 25 publications

Regeneration of 5-HT fibers in hippocampal heterotopia of methylazoxymethanol-induced micrencephalic rats after neonatal 5,7-DHT injection

Regeneration of 5-HT fibers in hippocampal heterotopia of methylazoxymethanol-induced micrencephalic rats after neonatal 5,7-DHT injection

Early postnatal administration of 5,7-dihydroxytryptamine: Effects on substance P and thyrotropin-releasing hormone neurons and terminals in rat brain

Perinatal supplementation of low doses of ethanol enhances 5-HT restoration in the central nervous system

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