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To die or not to die, does it change the function? Behavior of transgenic mice reveals a role for developmental cell
Laure Rondi-Reig1, Jean Mariani
1Neurobiologie des Processus Adaptatifs, Lab. Développement et Vieillissement du Sysème Nerveux (DVSN), Université P&M Curie, Paris, France. laure.rondi-reig@college-de-france.fr
Abstract:
In humans, perturbations in the developmental neuronal death leading to an excess of neurons could be associated with developmental neuropsychiatric disorders. Hu-bcl-2 transgenic mice appear to be a valuable tool to study the functional role of developmental programmed cell death. Indeed, the over-expression of the anti-apoptotic gene bcl-2 decreases developmental neuronal death and Hu-bcl-2 mice present supernumerary neurons in several brain regions. A detailed behavioral analysis of these mice revealed selective deficits. Hu-bcl-2 mice have normal vision, general activity and motor skills. Only the most complex behavior like anxiety and learning abilities are impaired in these mice.
Insights
Altering programmed cell death in mice by overexpressing the bcl-2 gene resulted in extra neurons and impaired learning and anxiety behaviors. This offers insights into developmental neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Perturbations in developmental neuronal death, leading to excess neurons, are linked to neuropsychiatric disorders.
- Programmed cell death is crucial for normal brain development.
- Understanding this process is key to addressing developmental disorders.
Purpose of the Study:
- To investigate the functional role of developmental programmed cell death using a novel transgenic mouse model.
- To determine the behavioral consequences of reduced neuronal death during development.
Main Methods:
- Generation of Hu-bcl-2 transgenic mice overexpressing the anti-apoptotic bcl-2 gene.
- Detailed behavioral analysis of Hu-bcl-2 mice, assessing vision, motor skills, anxiety, and learning.
- Neuroanatomical examination to identify regions with supernumerary neurons.
Main Results:
- Hu-bcl-2 mice exhibited a decrease in developmental neuronal death, resulting in supernumerary neurons in specific brain regions.
- Behavioral testing revealed normal vision, general activity, and motor skills in these mice.
- Significant deficits were observed in complex behaviors, specifically anxiety and learning abilities.
Conclusions:
- Overexpression of bcl-2 reduces developmental neuronal death, leading to excess neurons and specific behavioral impairments.
- Hu-bcl-2 mice serve as a valuable model for studying the link between neuronal development and neuropsychiatric conditions.
- These findings highlight the critical role of programmed cell death in shaping complex cognitive functions.