Tesis doctoral de Natalia Elizalde Urdiain
Chronic mild stress: neurobiological mechanisms involved in chronic depressive-like behaviour depression is a chronic disorder, often preceded by exposure to stress. Nowadays, there is an emerging clinical interest in mechanisms perpetuating episodes of depression and/or establishing increased vulnerability for relapse. Nevertheless, little attention has been paid to address these aspects in experimental models. In an attempt to respond to this clinical need, the long-term behavioural and neuroadaptive effects of the chronic mild stress (cms) model of depression with a course of antidepressant treatment (imipramine and paroxetine) have been studied. Cms induced a short and long-term altered depressive-like behavioural profile including anhedonia, helplessness as well as other highly comorbid symptoms such as anxiety and recognition memory impairment. Supporting the model validity, these long-lasting alterations were reversed by chronic antidepressant treatment. Cms induced long-lasting neurobiological alterations that were reversed by antidepressant treatment and that could be, therefore, involved in the perpetuation of depressive symptoms. Among them, an increased increased serotonergic activity in the dorsal raphe nucleus and a decreased decreased neuronal activity in the ca1 region, and of gad65 expression levels in the hippocampus. Cms also induced a set of long-lasting residual alterations following antidepressant discontinuation that affect especially to glutamate and gaba neurotransmitter systems in the ventral hippocampus. In addition, both cms and a genetic model of altered glutamate function showed an increased cortical expression of the activity regulated cytoskeletal protein (arc) after exposure to novelty. Finnally, neither hippocampal neurogenesis nor protein expression of synapsin 1 or synaptophysin were affected in the long-term. the long-term neurobiological alterations induced by cms could address molecular mechanisms involved in the perpetuation of the symptoms and in the acquired vulnerability of some remitted patients for relapse respectively.
Datos académicos de la tesis doctoral «Estrés crónico suave: mecanismos neurobiológicos implicados en la conducta depresiva crónica«
- Título de la tesis: Estrés crónico suave: mecanismos neurobiológicos implicados en la conducta depresiva crónica
- Autor: Natalia Elizalde Urdiain
- Universidad: Navarra
- Fecha de lectura de la tesis: 11/03/2010
Dirección y tribunal
- Director de la tesis
- Rosa María Tordera Baviera
- Tribunal
- Presidente del tribunal: joaquin del Rio zambrana
- ramón Trullas oliva (vocal)
- Andrés Ozaita mintegui (vocal)
- renato Corradetti (vocal)