Objective: The gene codifying for the neurotrophin Brain Derived Nurotrophic Factor (BDNF) is a stress-responsive gene and alteration in its expression may be important in producing some of the pathophysiological effects of stress in the hippocampus as seen in stress-related pathologies like depression. While the effects of stress procedures on the regulation of BDNF expression was widely investigated in hippocampus of healthy control animals, the stress-induced effects on BDNF hippocampal expression in “pathological” condition are still lacking. In order to deepen our knowledge in the understanding of the effects of an acute stressful procedure on molecular targets of synaptic plasticity we used transgenic mice with impaired glucocorticoid receptor (GR-i) expression that represent an animal model of depression. The hypothesis was tested that a single period of restraint stress (6 hours) affects BDNF mRNA expression in the hippocampus of GR-i mice differently than in wild-type (WT) mice. Methods: Using real time RT-PCR we evaluated the effects of a 6 hours acute stress on the levels of BDNF coding exon VIII and the activity regulated BDNF exon IV mRNA. In the WT and in the GR-i animals, the hippocampal levels of the two BDNF exons, immediately after the stress ended, were significantly lower in stressed animals with the respect to respective control unstressed animals. However, for the BDNF exon IV mRNA the reduction is most pronounced inWT animals and two-way ANOVA followed by Bonferroni posttest revealed a significant interaction between stress response and genotype at the level of BDNF exon IV mRNA expression. Results: The BDNF gene is a very complex gene regulated by a wide array of stimuli and signalling pathways. An electophoresis mobility shift assay (EMSA) was used to study DNA-binding activity of two transcription factors with an important role in controlling synaptic plasticity most likely trough an involvement BDNF: the cAMP responsive element binding (CREB) protein and the nuclear factor kB (Nf-kB). Taken together, our results show a different binding activity of these transcription factors in GR-i mice with respect to WT mice following acute stressful conditions. Conclusion: The identification of the molecular mechanisms activated by stress in GR-i mice model of depression may contribute to the development of new strategies that reducing neuron vulnerability to stress and prevent neurophatologocal alteration in the hippocampus.

Impaired stress-induced regulation of brain derived neurotrophic factor expression in hippocampus of glucocorticoid receptor impaired mice: Model of depression / Alboni, Silvia; Corsini, Daniela; Caggia, Federica; Benatti, Cristina; Capone, Giacomo; Barden, N; Blom, Johanna Maria Catharina; Tascedda, Fabio; Brunello, Nicoletta. - In: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY. - ISSN 1461-1457. - STAMPA. - Volume: 11 Supplement: 1:(2008), pp. 125-126. ((Intervento presentato al convegno 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) tenutosi a Munich, GERMANY nel JUL 13-17, 2008.

Impaired stress-induced regulation of brain derived neurotrophic factor expression in hippocampus of glucocorticoid receptor impaired mice: Model of depression

ALBONI, Silvia;CORSINI, Daniela;CAGGIA, Federica;BENATTI, Cristina;CAPONE, Giacomo;BLOM, Johanna Maria Catharina;TASCEDDA, Fabio;BRUNELLO, Nicoletta
2008-01-01

Abstract

Objective: The gene codifying for the neurotrophin Brain Derived Nurotrophic Factor (BDNF) is a stress-responsive gene and alteration in its expression may be important in producing some of the pathophysiological effects of stress in the hippocampus as seen in stress-related pathologies like depression. While the effects of stress procedures on the regulation of BDNF expression was widely investigated in hippocampus of healthy control animals, the stress-induced effects on BDNF hippocampal expression in “pathological” condition are still lacking. In order to deepen our knowledge in the understanding of the effects of an acute stressful procedure on molecular targets of synaptic plasticity we used transgenic mice with impaired glucocorticoid receptor (GR-i) expression that represent an animal model of depression. The hypothesis was tested that a single period of restraint stress (6 hours) affects BDNF mRNA expression in the hippocampus of GR-i mice differently than in wild-type (WT) mice. Methods: Using real time RT-PCR we evaluated the effects of a 6 hours acute stress on the levels of BDNF coding exon VIII and the activity regulated BDNF exon IV mRNA. In the WT and in the GR-i animals, the hippocampal levels of the two BDNF exons, immediately after the stress ended, were significantly lower in stressed animals with the respect to respective control unstressed animals. However, for the BDNF exon IV mRNA the reduction is most pronounced inWT animals and two-way ANOVA followed by Bonferroni posttest revealed a significant interaction between stress response and genotype at the level of BDNF exon IV mRNA expression. Results: The BDNF gene is a very complex gene regulated by a wide array of stimuli and signalling pathways. An electophoresis mobility shift assay (EMSA) was used to study DNA-binding activity of two transcription factors with an important role in controlling synaptic plasticity most likely trough an involvement BDNF: the cAMP responsive element binding (CREB) protein and the nuclear factor kB (Nf-kB). Taken together, our results show a different binding activity of these transcription factors in GR-i mice with respect to WT mice following acute stressful conditions. Conclusion: The identification of the molecular mechanisms activated by stress in GR-i mice model of depression may contribute to the development of new strategies that reducing neuron vulnerability to stress and prevent neurophatologocal alteration in the hippocampus.
Volume: 11 Supplement: 1
125
126
Alboni, Silvia; Corsini, Daniela; Caggia, Federica; Benatti, Cristina; Capone, Giacomo; Barden, N; Blom, Johanna Maria Catharina; Tascedda, Fabio; Brunello, Nicoletta
Impaired stress-induced regulation of brain derived neurotrophic factor expression in hippocampus of glucocorticoid receptor impaired mice: Model of depression / Alboni, Silvia; Corsini, Daniela; Caggia, Federica; Benatti, Cristina; Capone, Giacomo; Barden, N; Blom, Johanna Maria Catharina; Tascedda, Fabio; Brunello, Nicoletta. - In: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY. - ISSN 1461-1457. - STAMPA. - Volume: 11 Supplement: 1:(2008), pp. 125-126. ((Intervento presentato al convegno 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) tenutosi a Munich, GERMANY nel JUL 13-17, 2008.
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