| Autor: |
Deckert, Jürgen, Double, K., Koutsilieri, E., Wultsch, T., Chourbaji, S., Fritzen, S., Kittel, S., Grünblatt, E., Gerlach, M., Gutknecht, L., Chizat, F., Golfler, G., Schmitt, A., Gass, P., Lesch, K.-P., Reif, A. |
| Zdroj: |
Neuropsychiatric Disorders An Integrative Approach; 2007, p69-85, 17p |
| Abstrakt: |
The gaseous messenger nitric oxide (NO) has been implicated in a wide range of behaviors, including aggression, anxiety, depression, and cognitive functioning. To further elucidate the physiological role of NO and its down-stream mechanisms, we conducted behavioral and expressional phenotyping of mice lacking the neuronal isoform of nitric oxide synthase (NOS-I), the major source of NO in the central nervous system. No differences were observed in activity-related parameters; in contrast to the a priori hypothesis, derived from pharmacological treatments, depression-related tests (Forced Swim Test, Learned Helplessness) also yielded no significantly different results. A subtle anxiolytic phenotype however was present, with knockdown mice displaying a higher open arm time as compared to their respective wildtypes, yet all other investigated anxiety-related parameters were unchanged. The most prominent feature however was gender-independent cognitive impairment in spatial learning and memory, as assessed by the Water Maze test and an automatized holeboard paradigm. No significant dysregulation of monoamine transporters was evidenced by qRT PCR. To further examine the underlying molecular mechanisms, the transcriptome of knockdown animals was thus examined in the hippocampus, striatum and cerebellum by microarray analysis. A set of > 120 differentially expressed genes was identified, whereat the hippocampus and the striatum showed similar expressional profiles as compared to the cerebellum in hierarchical clustering. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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