Abstract
Adult neurogenesis is emerging as an important player in brain functions and homeostasis, while impaired or altered adult neurogenesis has been associated with a number of neuropsychiatric diseases, such as depression and epilepsy. Here we investigated the possibility that synapsins (Syns) I and II, beyond their known functions in developing and mature neurons, also play a role in adult neurogenesis. We performed a systematic evaluation of the distinct stages of neurogenesis in the hippocampal dentate gyrus of Syn I and Syn II knockout (KO) mice, before (2-months-old) and after (6-months-old) the appearance of the epileptic phenotype. We found that Syns I and II play an important role in the regulation of adult neurogenesis. In juvenile mice, Syn II deletion was associated with a specific decrease in the proliferation of neuronal progenitors, whereas Syn I deletion impaired the survival of newborn neurons. These defects were reverted after the appearance of the epileptic phenotype, with Syn I KO and Syn II KO mice exhibiting significant increases in survival and proliferation, respectively. Interestingly, long-term potentiation dependent on newborn neurons was present in both juvenile Syn mutants while, at later ages, it was only preserved in Syn II KO mice that also displayed an increased expression of brain-derived neurotrophic factor. This study suggests that Syns I and II play a role in adult neurogenesis and the defects in neurogenesis associated with Syn deletion may contribute to the alterations of cognitive functions observed in Syn-deficient mice.
Highlights
Adult neurogenesis is a structural form of neural plasticity that contributes to the maintenance of normal brain function and homeostasis [1]
Adult neurogenesis is emerging as an important player in brain functions and homeostasis, while impaired or altered adult neurogenesis has been associated with a number of neuropsychiatric diseases, such as depression and epilepsy
The reduction in adult hippocampal neurogenesis was not associated with any change in global dentate gyrus (DG) or hilus volumes that were similar across genotypes (Figure 1E)
Summary
Adult neurogenesis is a structural form of neural plasticity that contributes to the maintenance of normal brain function and homeostasis [1]. Within the hippocampal dentate gyrus (DG), newborn dentate granule cells are known to integrate into the pre-existing circuitry and play a substantial role in certain types of learning and memory and in the modulation of emotional behavior or anxiety [2, 3]. Among presynaptic proteins the Synapsins (Syns), an abundant family of neuron-specific synaptic vesicle (SV)-associated phosphoproteins, play important roles in both neuronal development and synaptic physiology [10, 11]. In mammals Syns are encoded by three distinct genes (SynI, SynII and SynIII) that generate more than ten isoforms by differential splicing. These transcripts are composed of a mosaic of individual and shared domains that are highly conserved during evolution, and their expression is developmentally regulated (see [11] for review)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
