Article

Enhanced long-term synaptic depression in an animal model of depression.

Department of Psychiatry, University of Freiburg, Freiburg, Germany.
Biological Psychiatry (Impact Factor: 9.25). 08/2007; 62(1):92-100. DOI: 10.1016/j.biopsych.2006.07.007
Source: PubMed

ABSTRACT A growing body of evidence suggests a disturbance of brain plasticity in major depression. In contrast to hippocampal neurogenesis, much less is known about the role of synaptic plasticity. Long-term potentiation (LTP) and long-term depression (LTD) regulate the strength of synaptic transmission and the formation of new synapses in many neural networks. Therefore, we examined the modulation of synaptic plasticity in the chronic mild stress animal model of depression.
Adult rats were exposed to mild and unpredictable stressors for 3 weeks. Thereafter, long-term synaptic plasticity was examined in the hippocampal CA1 region by whole-cell patch clamp measurements in brain slices. Neurogenesis was assessed by doublecortin immunostaining.
Exposure to chronic mild stress facilitated LTD and had no effect on LTP. Chronic application of the antidepressant fluvoxamine during the stress protocol prevented the facilitation of LTD and increased the extent of LTP induction. Neurogenesis in the dentate gyrus was impaired after chronic stress.
In addition to neurogenesis, long-term synaptic plasticity is an important and ubiquitous form of brain plasticity that is disturbed in an animal model of depression. Facilitated depression of synaptic transmission might impair function and structure of brain circuits involved in the pathophysiology of major depression. Antidepressants might counteract these alterations.

0 Bookmarks
 · 
115 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obwohl affektive Erkrankungen seit Jahrzehnten intensiv untersucht werden, besteht überraschend großer Forschungsbedarf bezüglich ihrer Ätiopathogenese. So existiert zwar eine Fülle an neurobiologischen und psychosozialen Erklärungsansätzen, jedoch sind viele der in ihnen postulierten ursächlichen Faktoren noch nicht befriedigend empirisch bewiesen und in übergreifende Modelle integriert. Am besten belegt ist bisher, dass die genetische Belastung eine entscheidende Rolle spielt. Es wird jedoch lediglich die Vulnerabilität für die Erkrankung vererbt, d. h., eine Depression kann sich selbst bei einer entsprechenden genetischen Disposition erst im Zusammenspiel mit psychosozialen Auslösefaktoren manifestieren. Aus psychosozialer Perspektive legen die verschiedenen Schulen bezüglich dieser Faktoren unterschiedliche Schwerpunkte: Während psychoanalytische Theorien die Vulnerabilität für eine Depression vor allem in einem in der frühen Kindheit entstandenen fragilen Selbstwertsystem sehen, subsumieren behavioral-kognitive Ansätze unter prädisponierenden Faktoren dysfunktionale Kognitionen gepaart mit gelernter Hilflosigkeit und Verhaltensdefiziten sowie mit einem Mangel an positiv verstärkenden Aktivitäten. Interpersonelle Theorien gehen hingegen immer von einem gestörten bzw. dysfunktionalen psychosozialen und interpersonellen Kontext aus. In der Ätiopathogenese der schwer zu behandelnden chronischen Depression scheinen insbesondere frühe Traumata sowie ein präoperatorisches Denken eine wichtige Rolle zu spielen. Zusammenfassend kann festgestellt werden, dass nur bio-psycho-soziale Modelle, die biologische, neurobiologische und psychosoziale Vulnerabilitäten und Stressoren berücksichtigen, es ermöglichen, die Ätiopathogenese der Depression zu beschreiben und zu ergründen.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 01/2008; 51(4). · 0.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Depression is the most common psychiatric comorbidity in epilepsy patients. The lack of success with current pharmacological interventions for this patient population, highlights the importance of optimizing non-pharmacological neuromodulatory treatments such as vagus nerve stimulation (VNS). Studies on the antidepressant effect of VNS in epilepsy patients may be confounded by concurrent antiepileptic drug therapy. To date, studies in epilepsy models overcoming this problem are lacking. Objective We investigated whether VNS affects anhedonia, a key symptom of major depression, in the kainic acid rat model for temporal lobe epilepsy. Methods Anhedonia was assessed in kainic acid (KA) and saline (SAL) injected rats using the saccharin preference test (SPT). To exclude differences in taste perception, the quinine aversion test (QAT) was performed. Both groups were randomly subdivided in a VNS and a SHAM group, yielding 4 experimental arms: KA-VNS, KA-SHAM, SAL-VNS and SAL-SHAM. Both VNS groups received 2 weeks of VNS, while the SHAM groups were not stimulated. Thereafter, the SPT and QAT were repeated. Results Saccharin preference was significantly reduced in the KA compared to the SAL rats (p<0.05), without differences in quinine aversion. Two weeks of VNS significantly increased the saccharin preference in the KA-VNS group (p<0.05), while it had no effect on quinine aversion. No effects of VNS or SHAM were found in the other groups. Conclusion The KA rats displayed anhedonia which was significantly decreased by VNS, indicating that this neuromodulatory treatment could likewise diminish depressive symptoms in patients suffering from temporal lobe epilepsy and comorbid depression.
    Brain Stimulation 09/2014; · 4.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neither pain, nor depression exist as independent phenomena per se, they are highly subjective inner states, formed by our brain and built on the bases of our experiences, cognition and emotions. Chronic pain is associated with changes in brain physiology and anatomy. It has been suggested that the neuronal activity underlying subjective perception of chronic pain may be divergent from the activity associated with acute pain. We will discuss the possible common pathophysiological mechanism of chronic pain and depression with respect to the default mode network of the brain, neuroplasticity and the effect of antidepressants on these two pathological conditions. The default mode network of the brain has an important role in the representation of introspective mental activities and therefore can be considered as a nodal point, common for both chronic pain and depression. Neuroplasticity which involves molecular, cellular and synaptic processes modifying connectivity between neurons and neuronal circuits can also be affected by pathological states such as chronic pain or depression. We suppose that pathogenesis of depression and chronic pain shares common negative neuroplastic changes in the central nervous system (CNS). The positive impact of antidepressants would result in a reduction of these pathological cellular/molecular processes and in the amelioration of symptoms, but it may also increase survival times and quality of life of patients with chronic cancer pain.
    Frontiers in Behavioral Neuroscience 01/2014; 8:99. · 4.76 Impact Factor

Similar Publications