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Neurogenic and angiogenic actions of electroconvulsive seizures in adult rat brain

Hellsten, Johan LU (2005) In Lund University Faculty of Medicine Doctoral Dissertation Series
Abstract
In the current thesis, the neurogenic and angiogenic response to electroconvulsive seizure (ECS)-treatment was investigated in the adult rat brain. ECS-treatment is an animal model for the antidepressant treatment electroconvulsive therapy (ECT), which is considered to be the most effective antidepressant treatment modality today, however with not yet fully understood modes of action. Depression, which is a common and devastating illness has recently been proposed to be caused by a decreased hippocampal neurogenesis and cellular plasticity in general, possibly due to elevated levels of the stress hormone cortisol, manifesting itself as a reduction in hippocampal volume. In the current thesis, ECS-treatment was shown to be able to oppose... (More)
In the current thesis, the neurogenic and angiogenic response to electroconvulsive seizure (ECS)-treatment was investigated in the adult rat brain. ECS-treatment is an animal model for the antidepressant treatment electroconvulsive therapy (ECT), which is considered to be the most effective antidepressant treatment modality today, however with not yet fully understood modes of action. Depression, which is a common and devastating illness has recently been proposed to be caused by a decreased hippocampal neurogenesis and cellular plasticity in general, possibly due to elevated levels of the stress hormone cortisol, manifesting itself as a reduction in hippocampal volume. In the current thesis, ECS-treatment was shown to be able to oppose stress hormone-induced decrease in hippocampal neurogenesis and also induce proliferation of non-neuronal cells. A large majority of these cells were identified as being endothelial cells, and neurogenesis and angiogenesis in response to ECS-treatment seemingly occurred in concert. In addition to neurogenesis, ECS-treatment induced strong neuronal activation in the hypothalamus, co-localising with a strong angiogenic response. Endothelial cells have been shown to influence neuronal and glial function and we hypothesise that the increase in hypothalamic endothelial cell proliferation could for example influence neuroendocrine signaling. Besides possibly influencing neuronal and glial function, endothelial cells are building blocks of blood vessels. We detect a strong angiogenic response in the hippocampus, which in fact results in a 16% increase in vessel length in the molecular layer of the dentate gyrus. This finding has important implications for the trophic actions of ECS-treatment. In addition to counteracting decreases in neurogenesis, ECS-treatment increase the vascularization of a structure that has been shown to be vulnerable to stress and decrease in size in depressed patients. Understanding this angiogenic response and possibly being able to stimulate it by other means than ECS-treatment could possibly lead to the development of new and more effective antidepressant treatments. (Less)
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author
supervisor
opponent
  • Professor Reid, Ian, University of Aberdeen
organization
publishing date
type
Thesis
publication status
published
subject
keywords
vävnadskultur, Psychiatry, clinical psychology, psychosomatics, klinisk psykologi, psykosomatik, histokemi, cytokemi, Histologi, tissue culture, histochemistry, cytochemistry, Histology, Biology, Biologi, electroconvulsive seizures, hippocampus, depression, angiogenesis, neurogenesis, Psykiatri
in
Lund University Faculty of Medicine Doctoral Dissertation Series
pages
112 pages
publisher
Molecular Psychiatry Unit
defense location
Segerfalksalen Wallenberg Neuroscience Center BMC A10 22184 Lund Sweden
defense date
2005-09-29 09:00:00
ISSN
1652-8220
ISBN
91-628-6592-7
language
English
LU publication?
yes
additional info
Johan Hellsten, Malin Wennström, Paul Mohapel, Christine T. Ekdahl, Johan Bengzon and Anders Tingström. 2002. Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment Eur J Neurosci, vol 16 pp 283-290. Blackwell
J. Hellsten, M. Wennström, J. Bengzon, P. Mohapel and A. Tingström. 2004. Electroconvulsive seizures induce endothelial cell proliferation in adult rat hippocampus Biological Psychiatry, vol 55 pp 420-427. Elsevier
J. Ekstrand, J. Hellsten, M. Wennström and A. Tingström. 2005. Inhibition of endothelial cell proliferation does not prevent electroconvulsive seizure-induced neural precursor proliferation in adult rat hippocampus. (manuscript)
J. Hellsten, M.J. West, A. Arvidsson, J. Ekstrand, L. Jansson, M. Wennström and A. Tingström. 2005. Electroconvulsive seizures induce angiogenesis in adult rat hippocampus Biol Psychiatry, (inpress)
L. Jansson, J. Hellsten and A. Tingström. 2005. Region specific hypothalamic neuronal activation and endothelial cell proliferation in response to electroconvulsive seizures (submitted)
id
4c151ea7-7892-4418-8199-75ed22437b22 (old id 545303)
date added to LUP
2016-04-01 17:03:11
date last changed
2019-05-21 21:46:09
@phdthesis{4c151ea7-7892-4418-8199-75ed22437b22,
  abstract     = {{In the current thesis, the neurogenic and angiogenic response to electroconvulsive seizure (ECS)-treatment was investigated in the adult rat brain. ECS-treatment is an animal model for the antidepressant treatment electroconvulsive therapy (ECT), which is considered to be the most effective antidepressant treatment modality today, however with not yet fully understood modes of action. Depression, which is a common and devastating illness has recently been proposed to be caused by a decreased hippocampal neurogenesis and cellular plasticity in general, possibly due to elevated levels of the stress hormone cortisol, manifesting itself as a reduction in hippocampal volume. In the current thesis, ECS-treatment was shown to be able to oppose stress hormone-induced decrease in hippocampal neurogenesis and also induce proliferation of non-neuronal cells. A large majority of these cells were identified as being endothelial cells, and neurogenesis and angiogenesis in response to ECS-treatment seemingly occurred in concert. In addition to neurogenesis, ECS-treatment induced strong neuronal activation in the hypothalamus, co-localising with a strong angiogenic response. Endothelial cells have been shown to influence neuronal and glial function and we hypothesise that the increase in hypothalamic endothelial cell proliferation could for example influence neuroendocrine signaling. Besides possibly influencing neuronal and glial function, endothelial cells are building blocks of blood vessels. We detect a strong angiogenic response in the hippocampus, which in fact results in a 16% increase in vessel length in the molecular layer of the dentate gyrus. This finding has important implications for the trophic actions of ECS-treatment. In addition to counteracting decreases in neurogenesis, ECS-treatment increase the vascularization of a structure that has been shown to be vulnerable to stress and decrease in size in depressed patients. Understanding this angiogenic response and possibly being able to stimulate it by other means than ECS-treatment could possibly lead to the development of new and more effective antidepressant treatments.}},
  author       = {{Hellsten, Johan}},
  isbn         = {{91-628-6592-7}},
  issn         = {{1652-8220}},
  keywords     = {{vävnadskultur; Psychiatry; clinical psychology; psychosomatics; klinisk psykologi; psykosomatik; histokemi; cytokemi; Histologi; tissue culture; histochemistry; cytochemistry; Histology; Biology; Biologi; electroconvulsive seizures; hippocampus; depression; angiogenesis; neurogenesis; Psykiatri}},
  language     = {{eng}},
  publisher    = {{Molecular Psychiatry Unit}},
  school       = {{Lund University}},
  series       = {{Lund University Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Neurogenic and angiogenic actions of electroconvulsive seizures in adult rat brain}},
  url          = {{https://lup.lub.lu.se/search/files/4860004/545309.pdf}},
  year         = {{2005}},
}