Impact of Targeted Deletion of the Circadian Clock Gene Bmal1 in Excitatory Forebrain Neurons on Adult Neurogenesis and Olfactory Function

• Published in: International journal of molecular sciences Vol. 21; no. 4; p. 1394
• Main Authors: Ali, Amira A H, Tundo-Lavalle, Federica, Hassan, Soha A, Pfeffer, Martina, Stahr, Anna, von Gall, Charlotte
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 19-02-2020; MDPI AG
• Subjects: Animals; ARNTL Transcription Factors - genetics; ARNTL Transcription Factors - metabolism; Astrocytes - metabolism; Behavior Rating Scale; Cell Adhesion Molecules, Neuronal - genetics; Cell Adhesion Molecules, Neuronal - metabolism; Cell Movement - genetics; Cell Proliferation - genetics; Cell Survival - genetics; circadian clock; Circadian Clocks - genetics; Circadian Rhythm - genetics; Circadian Rhythm - physiology; Dentate Gyrus - growth & development; Dentate Gyrus - metabolism; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; hippocampus; Hippocampus - metabolism; Lateral Ventricles - metabolism; Male; Mice; Mice, Knockout; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; neurogenesis; Neurogenesis - genetics; Neurons - metabolism; Olfactory Bulb - metabolism; oxidative stress; Oxidative Stress - genetics; Reelin Protein; Sequence Deletion; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; neurogenesis; hippocampus; circadian clock; oxidative stress
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms21041394

The circadian system is an endogenous timekeeping system that synchronizes physiology and behavior with the 24 h solar day. Mice with total deletion of the core circadian clock gene Bmal1 show circadian arrhythmicity, cognitive deficits, and accelerated age-dependent decline in adult neurogenesis as a consequence of increased oxidative stress. However, it is not yet known if the impaired adult neurogenesis is due to circadian disruption or to loss of the Bmal1 gene function. Therefore, we investigated oxidative stress and adult neurogenesis of the two principle neurogenic niches, the hippocampal subgranular zone and the subventricular zone in mice with a forebrain specific deletion of
(
), which show regular circadian rhythmicity. Moreover, we analyzed the morphology of the olfactory bulb, as well as olfactory function in
mice. In
mice, oxidative stress was increased in subregions of the hippocampus and the olfactory bulb but not in the neurogenic niches. Consistently, adult neurogenesis was not affected in
mice. Although Reelin expression in the olfactory bulb was higher in
mice as compared to wildtype mice (
, the olfactory function was not affected. Taken together, the targeted deletion of
in mouse forebrain neurons is associated with a regional increase in oxidative stress and increased Reelin expression in the olfactory bulb but does not affect adult neurogenesis or olfactory function.