Orchestrated regulation of Nogo receptors, LOTUS, AMPA receptors and BDNF in an ECT model suggests opening and closure of a window of synaptic plasticity.
Electroconvulsive therapy (ECT) is an efficient and relatively fast acting treatment for depression. However, one severe side effect of the treatment is retrograde amnesia, which in certain cases can be long-term. The mechanisms behind the antidepressant effect and the amnesia are not well understood. We hypothesized that ECT causes transient downregulation of key molecules needed to stabilize synaptic structure and to prevent Ca2+ influx, and a simultaneous increase in neurotrophic factors, thus providing a short time window of increased structural synaptic plasticity. Here we followed regulation of NgR1, NgR3, LOTUS, BDNF, and AMPA subunits GluR1 and GluR2 flip and flop mRNA levels in hippocampus at 2, 4, 12, 24, and 72 hours after a single episode of induced electroconvulsive seizures (ECS) in rats. NgR1 and LOTUS mRNA levels were transiently downregulated in the dentate gyrus 2, 4, 12 and 4, 12, 24 h after ECS treatment, respectively. GluR2 flip, flop and GluR1 flop were downregulated at 4 h. GluR2 flip remained downregulated at 12 h. In contrast, BDNF, NgR3 and GluR1 flip mRNA levels were upregulated. Thus, ECS treatment induces a transient regulation of factors important for neuronal plasticity. Our data provide correlations between ECS treatment and molecular events compatible with the hypothesis that both effects and side effects of ECT may be caused by structural synaptic rearrangements.
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Max
M
Nordgren
Tobias
T
Karlsson
Maria
M
Svensson
Josefin
J
Koczy
Anna
A
Josephson
Lars
L
Olson
Anders
A
Tingström
Stefan
S
Brené
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D018891:Dentate Gyrus / Q000378:metabolism*; D015536:Down-Regulation; D004565:Electroconvulsive Therapy; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D008297:Male; D009185:Myelin Proteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D000070816:Nogo Receptor 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070816:Nogo Receptor 1; D018091:Receptors, AMPA; D011956:Receptors, Cell Surface; C583728:LOTUS protein, rat; C486581:Rtn4r protein, rat; C104722:glutamate receptor ionotropic, AMPA 2