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Specific functions of grafted locus coeruleus neurons in the kindling model of epilepsy

Bengzon, J LU ; Kokaia, Z LU orcid and Lindvall, O LU (1993) In Experimental Neurology 122(1). p.143-154
Abstract

Grafts of fetal noradrenaline (NA)-rich locus coeruleus (LC) tissue implanted bilaterally into the hippocampus in 6-hydroxydopamine (6-OHDA) treated, hyperexcitable rats retard seizure development in hippocampal kindling. We report that bilateral intrahippocampal LC grafts failed to affect the severity of seizures when implanted in 6-OHDA-treated, already kindled rats. Furthermore, a noradrenergic hyperinnervation of the hippocampus, produced by grafting fetal LC tissue into the intact brain, did not influence hippocampal kindling development. Kindling leads to long-term reduction in basal hippocampal NA release from the intrinsic locus coeruleus system as monitored using intracerebral microdialysis. This deficit could be reversed by... (More)

Grafts of fetal noradrenaline (NA)-rich locus coeruleus (LC) tissue implanted bilaterally into the hippocampus in 6-hydroxydopamine (6-OHDA) treated, hyperexcitable rats retard seizure development in hippocampal kindling. We report that bilateral intrahippocampal LC grafts failed to affect the severity of seizures when implanted in 6-OHDA-treated, already kindled rats. Furthermore, a noradrenergic hyperinnervation of the hippocampus, produced by grafting fetal LC tissue into the intact brain, did not influence hippocampal kindling development. Kindling leads to long-term reduction in basal hippocampal NA release from the intrinsic locus coeruleus system as monitored using intracerebral microdialysis. This deficit could be reversed by intrahippocampal LC grafts implanted into previously kindled rats. However, these unilateral grafts had no effect on the severity of the kindled convulsions despite a noradrenergic hyperinnervation of the hippocampus around the grafts. In conclusion, these data show a distinct functional specificity of intrahippocampal LC grafts in the kindling model of epilepsy. Similar to the intrinsic noradrenergic system, the grafted neurons have a major inhibitory influence on seizure development but are ineffective against established convulsions.

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author
; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Brain/drug effects, Epilepsy/etiology, Hippocampus/metabolism, Injections, Injections, Intraventricular, Kindling, Neurologic, Locus Coeruleus/cytology, Male, Neurons/physiology, Norepinephrine/metabolism, Oxidopamine/pharmacology, Rats, Rats, Sprague-Dawley
in
Experimental Neurology
volume
122
issue
1
pages
143 - 154
publisher
Elsevier
external identifiers
  • pmid:8339784
  • scopus:0027205476
ISSN
0014-4886
DOI
10.1006/exnr.1993.1115
language
English
LU publication?
no
id
e8ca14bc-f4f8-421f-9a57-330f7f18403b
date added to LUP
2019-06-25 10:42:24
date last changed
2024-01-01 13:06:48
@article{e8ca14bc-f4f8-421f-9a57-330f7f18403b,
  abstract     = {{<p>Grafts of fetal noradrenaline (NA)-rich locus coeruleus (LC) tissue implanted bilaterally into the hippocampus in 6-hydroxydopamine (6-OHDA) treated, hyperexcitable rats retard seizure development in hippocampal kindling. We report that bilateral intrahippocampal LC grafts failed to affect the severity of seizures when implanted in 6-OHDA-treated, already kindled rats. Furthermore, a noradrenergic hyperinnervation of the hippocampus, produced by grafting fetal LC tissue into the intact brain, did not influence hippocampal kindling development. Kindling leads to long-term reduction in basal hippocampal NA release from the intrinsic locus coeruleus system as monitored using intracerebral microdialysis. This deficit could be reversed by intrahippocampal LC grafts implanted into previously kindled rats. However, these unilateral grafts had no effect on the severity of the kindled convulsions despite a noradrenergic hyperinnervation of the hippocampus around the grafts. In conclusion, these data show a distinct functional specificity of intrahippocampal LC grafts in the kindling model of epilepsy. Similar to the intrinsic noradrenergic system, the grafted neurons have a major inhibitory influence on seizure development but are ineffective against established convulsions.</p>}},
  author       = {{Bengzon, J and Kokaia, Z and Lindvall, O}},
  issn         = {{0014-4886}},
  keywords     = {{Animals; Brain/drug effects; Epilepsy/etiology; Hippocampus/metabolism; Injections; Injections, Intraventricular; Kindling, Neurologic; Locus Coeruleus/cytology; Male; Neurons/physiology; Norepinephrine/metabolism; Oxidopamine/pharmacology; Rats; Rats, Sprague-Dawley}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{143--154}},
  publisher    = {{Elsevier}},
  series       = {{Experimental Neurology}},
  title        = {{Specific functions of grafted locus coeruleus neurons in the kindling model of epilepsy}},
  url          = {{http://dx.doi.org/10.1006/exnr.1993.1115}},
  doi          = {{10.1006/exnr.1993.1115}},
  volume       = {{122}},
  year         = {{1993}},
}