Title:Lithium Restores Age-related Olfactory Impairment in the Ts65Dn Mouse Model of Down Syndrome
Volume: 16
Issue: 7
Author(s): Sandra Guidi, Patrizia Bianchi, Fiorenza Stagni, Andrea Giacomini, Marco Emili, Stefania Trazzi, Elisabetta Ciani and Renata Bartesaghi*
Affiliation:
- Department of Biomedical and Neuromotor Sciences, Physiology Building, Piazza di Porta San Donato 2, I-40126 BOLOGNA BO,Italy
Keywords:
Aging, Dentate gyrus, Down syndrome, Lithium, Neurogenesis, Olfactory bulb, Olfactory function, Subventricular
zone.
Abstract: Background & Objective: Down syndrome, a genetic condition caused by triplication of
chromosome 21, is characterized by widespread neurogenesis reduction and cognitive impairment.
Unlike other brain functions, smell is not impaired at early life stages and olfactory deterioration
begins to appear in adulthood. Similarly to individuals with Down syndrome, in the Ts65Dn mouse
model of Down syndrome smell function is normal at early life stages. Smell impairment only appears
in adulthood associated with a reduction in the number of new granule neurons migrated to the
olfactory bulb from the subventricular zone. Based on evidence that lithium positively impacts
neurogenesis, the goal of current study was to establish whether treatment with lithium restores
olfactory bulb neurogenesis and olfactory performance in middle-aged Ts65Dn mice.
Method: Euploid and Ts65Dn mice aged 13 months were treated with lithium chow or control chow for
one month. Before the end of treatment, mice were injected with BrdU, in order to label proliferating
cells. Results showed that in Ts65Dn mice lithium treatment restored the number of neural precursor cells
in the subventricular zone of the lateral ventricle, rostral migratory stream and olfactory bulb. This effect
was accompanied by restoration of olfactory performance. Unlike in olfactory neurogenic regions,
treatment had no neurogenesis-enhancing effect on the subgranular zone of the hippocampal dentate
gyrus, indicating that lithium has no generalized positive effect on the brain.
Conclusion: Results suggest that lithium may have a positive impact in brain disorders that, similarly
to Down syndrome, are characterized by olfactory decline and neurogenesis impairment in the
subventricular zone.
