ABSTRACT
BACKGROUND: Long-term synaptic plasticity is a basic ability of the brain to dynamically adapt to external stimuli and regulate synaptic strength and ultimately network function. It is dysregulated by behavioral stress in animal models of depression and in humans with major depressive disorder. Antidepressants have been shown to restore disrupted synaptic plasticity in both animal models and humans; however, the underlying mechanism is unclear. METHODS: We examined modulation of synaptic plasticity by selective serotonin reuptake inhibitors (SSRIs) in hippocampal brain slices from wild-type rats and serotonin transporter (SERT) knockout mice. Recombinant voltage-gated calcium (Ca2+) channels in heterologous expression systems were used to determine the modulation of Ca2+ channels by SSRIs. We tested the behavioral effects of SSRIs in the chronic behavioral despair model of depression both in the presence and in the absence of SERT. RESULTS: SSRIs selectively inhibited hippocampal long-term depression. The inhibition of long-term depression by SSRIs was mediated by a direct block of voltage-activated L-type Ca2+ channels and was independent of SERT. Furthermore, SSRIs protected both wild-type and SERT knockout mice from behavioral despair induced by chronic stress. Finally, long-term depression was facilitated in animals subjected to the behavioral despair model, which was prevented by SSRI treatment. CONCLUSIONS: These results showed that antidepressants protected synaptic plasticity and neuronal circuitry from the effects of stress via a modulation of Ca2+ channels and synaptic plasticity independent of SERT. Thus, L-type Ca2+ channels might constitute an important signaling hub for stress response and for pathophysiology and treatment of depression.
Subject(s)
Antidepressive Agents/therapeutic use , Calcium Channels, L-Type/metabolism , RNA-Binding Proteins/metabolism , Stress, Psychological/drug therapy , Synaptic Transmission/drug effects , Age Factors , Animals , CHO Cells , Cadmium Chloride/pharmacology , Calcium Channel Blockers/pharmacology , Calcium Channels, L-Type/genetics , Cricetulus , Disease Models, Animal , Electric Stimulation , Female , Fluvoxamine/therapeutic use , HEK293 Cells , Hindlimb Suspension/psychology , Hippocampus/cytology , Humans , In Vitro Techniques , Male , Membrane Potentials/drug effects , Membrane Potentials/genetics , Nifedipine/pharmacology , Paroxetine/pharmacology , Patch-Clamp Techniques , Piperazines/pharmacology , Pyridines/pharmacology , RNA-Binding Proteins/genetics , Rats , Rats, Transgenic , Rats, Wistar , Serotonin/pharmacology , Serotonin Antagonists/pharmacology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Stress, Psychological/genetics , Swimming/psychology , Synaptic Transmission/genetics , TransfectionABSTRACT
Unilateral thalamic infarction is a rare condition in adults. This is a case report of a young child presenting with left-sided hemiparesis of sudden onset due to an unilateral venous thalamic infarction. This was attributed to an asymmetric thrombosis of the cerebral internal veins, a partial thrombosis of the vein of Galen and straight sinus. Magnetic resonance imaging resulted primarily in the differential diagnosis of a cerebral tumor or an intracerebral abscess, leading to stereotactic puncture. Subsequent magnetic resonance venography facilitated the correct diagnosis. Heparin-induced thrombocytopenia necessitated anticoagulation treatment with hirudin and later, warfarin. The patient made a complete recovery. We conclude that unclear unilateral thalamic lesions might be symptomatic of a cerebral deep venous thrombosis and might mimic a thalamic tumor. In uncertain cases, we suggest rapid performance of magnetic resonance angiography.