Lack of Sez6 Family Proteins Impairs Motor Functions, Short-Term Memory, and Cognitive Flexibility and Alters Dendritic Spine Properties
| Autor: | Hiroshi Takeshima, Jenny M. Gunnersen, Martina Pigoni, Stefan F. Lichtenthaler, Tim D. Aumann, Kathryn M. Munro, Amelia Nash |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Mice 129 Strain Dendritic spine Dendritic Spines Cognitive Neuroscience Hippocampus Morris water navigation task Nerve Tissue Proteins metabolism [Hippocampus] Biology Mice 03 medical and health sciences Cellular and Molecular Neuroscience Cognition physiology [Locomotion] 0302 clinical medicine Animals ddc:610 genetics [Nerve Tissue Proteins] 030304 developmental biology Mice Knockout 0303 health sciences deficiency [Nerve Tissue Proteins] Working memory physiology [Cognition] Cognitive flexibility Motor coordination Mice Inbred C57BL Memory Short-Term pathology [Hippocampus] metabolism [Dendritic Spines] Motor Skills physiology [Memory Short-Term] Synaptic plasticity pathology [Dendritic Spines] Motor learning Neuroscience Locomotion physiology [Motor Skills] 030217 neurology & neurosurgery |
| Zdroj: | Cerebral cortex 30(4), 2167-2184 (2019). doi:10.1093/cercor/bhz230 |
| ISSN: | 1460-2199 1047-3211 |
| DOI: | 10.1093/cercor/bhz230 |
| Popis: | Seizure-related gene 6 (Sez6), Sez6-Like (Sez6L), and Sez6-Like 2 (Sez6L2) comprise a family of homologous proteins widely expressed throughout the brain that have been linked to neurodevelopmental and psychiatric disorders. Here, we use Sez6 triple knockout (TKO) mice, which lack all three Sez6 family proteins, to demonstrate that Sez6 family proteins regulate dendritic spine structure and cognitive functions, motor learning, and maintenance of motor functions across the lifespan. Compared to WT controls, we found that Sez6 TKO mice had impaired motor learning and their motor coordination was negatively affected from 6 weeks old and declined more rapidly as they aged. Sez6 TKO mice had reduced spine density in the hippocampus and dendritic spines were shifted to more immature morphologies in the somatosensory cortex. Cognitive testing revealed that they had enhanced stress responsiveness, impaired working, and spatial short-term memory but intact spatial long-term memory in the Morris water maze albeit accompanied by a reversal deficit. Our study demonstrates that the lack of Sez6 family proteins results in phenotypes commonly associated with neuropsychiatric disorders making it likely that Sez6 family proteins contribute to the complex etiologies of these disorders. |
| Databáze: | OpenAIRE |
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