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View Abstract
The influence of chronic electroconvulsive seizure (ECS) or antidepressant drug treatments on expression of brain-derived neurotrophic factor (BDNF) and its receptor, trkB, was examined by in situ hybridization and Northern blot. In frontal cortex, acute ECS increased BDNF mRNA approximately twofold, an effect significantly augmented by a prior course of chronic ECS treatment (10 d). In the hippocampus, the influence of chronic ECS varied between the major subfields. In the dentate gyrus granule cell layer, chronic ECS decreased the acute induction of BDNF and trkB mRNA by approximately 50%, but prolonged their expression: levels remained elevated two- to threefold 18 hr later after the last chronic ECS treatment, but returned to control 18 hr after acute ECS. In CA3 and CA1 pyramidal cell layers, chronic ECS significantly elevated the acute induction of BDNF, and tended to prolong the expression of BDNF and trkB mRNA. A similar effect was observed in layer 2 of the piriform cortex, where chronic ECS significantly increased the acute induction and prolonged the expression of BDNF and trkB mRNA. Chronic (21 d), but not acute (1 d), administration of several different antidepressant drugs, including tranylcypromine, sertraline, desipramine, or mianserin, significantly increased BDNF mRNA and all but mianserin increased trkB mRNA in hippocampus. In contrast, chronic administration of nonantidepressant psychotropic drugs, including morphine, cocaine, or haloperidol, did not increase levels of BDNF mRNA. Furthermore, chronic administration of ECS or antidepressant drugs completely blocked the down-regulation of BDNF mRNA in the hippocampus in response to restraint stress. The enhanced induction and prolonged expression of BDNF in response to chronic ECS and antidepressant drug treatments could promote neuronal survival, and protect neurons from the damaging effects of stress.
Protocol Steps
1
Chronic ECS Treatment
Administer chronic electroconvulsive seizure treatment to rats
10 daysNot specified
Note: This is the chronic ECS treatment condition
View evidence from paper
“an effect significantly augmented by a prior course of chronic ECS treatment (10 d)”
2
Acute ECS Administration
Administer acute electroconvulsive seizure treatment following chronic ECS treatment or as standalone acute treatment
Single acute treatmentNot specified
Note: Can be administered after chronic ECS or as acute-only control
View evidence from paper
“In frontal cortex, acute ECS increased BDNF mRNA approximately twofold”
3
Chronic Antidepressant Drug Administration
Administer antidepressant drugs chronically to rats. Drugs tested include tranylcypromine, sertraline, desipramine, or mianserin
21 daysNot specified
Note: Chronic administration only; acute administration (1 day) did not increase BDNF mRNA
View evidence from paper
“Chronic (21 d), but not acute (1 d), administration of several different antidepressant drugs, including tranylcypromine, sertraline, desipramine, or mianserin, significantly increased BDNF mRNA”
4
Non-antidepressant Psychotropic Drug Administration (Control)
Administer non-antidepressant psychotropic drugs chronically as control conditions. Drugs tested include morphine, cocaine, or haloperidol
Chronic administrationNot specified
Note: These drugs serve as negative controls and did not increase BDNF mRNA levels
View evidence from paper
“chronic administration of nonantidepressant psychotropic drugs, including morphine, cocaine, or haloperidol, did not increase levels of BDNF mRNA”
5
Restraint Stress Application
Apply restraint stress to rats to induce down-regulation of BDNF mRNA in hippocampus
Not specifiedNot specified
Note: Restraint stress causes BDNF mRNA down-regulation which is prevented by prior ECS or antidepressant treatment
View evidence from paper
“chronic administration of ECS or antidepressant drugs completely blocked the down-regulation of BDNF mRNA in the hippocampus in response to restraint stress”
6
Brain Tissue Collection and Analysis - Acute ECS Response
Collect brain tissue and analyze BDNF and trkB mRNA expression using in situ hybridization and Northern blot
Immediately after acute ECS or at specified timepointsNot specified
Note: Acute ECS increased BDNF mRNA approximately twofold in frontal cortex
View evidence from paper
“In frontal cortex, acute ECS increased BDNF mRNA approximately twofold”
7
Brain Tissue Collection and Analysis - Delayed Timepoint
Collect brain tissue 18 hours after the last chronic ECS treatment to assess prolonged BDNF and trkB mRNA expression
18 hours after last chronic ECS treatmentNot specified
Note: In dentate gyrus, levels remained elevated two- to threefold 18 hr after last chronic ECS but returned to control 18 hr after acute ECS
View evidence from paper
“levels remained elevated two- to threefold 18 hr later after the last chronic ECS treatment, but returned to control 18 hr after acute ECS”
8
Regional Brain Analysis
Analyze BDNF and trkB mRNA expression in specific brain regions: frontal cortex, hippocampus (dentate gyrus, CA3, CA1), and piriform cortex layer 2
Not specifiedNot specified
Note: Different brain regions showed different patterns of BDNF and trkB mRNA regulation
View evidence from paper
“In the hippocampus, the influence of chronic ECS varied between the major subfields”