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Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse

1
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
2
Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
*
Authors to whom correspondence should be addressed.
These Authors contributed equally to the work.
Antioxidants 2019, 8(6), 163; https://doi.org/10.3390/antiox8060163
Received: 18 April 2019 / Revised: 29 May 2019 / Accepted: 5 June 2019 / Published: 6 June 2019
(This article belongs to the Special Issue Polyphenolic Compounds as Neuroprotective Agents)
No therapies currently exist for intellectual disability in Down syndrome (DS). In view of its similarities with DS, including learning and memory (L&M) defects, the Ts65Dn mouse model of DS is widely used for the design of therapy. 7,8-dihydroxyflavone (7,8-DHF), a flavonoid that targets the tropomyosin-related kinase B (TrkB) receptor of brain-derived neurotrophic factor (BDNF), exerts positive effects in various brain disease models. Based on previous demonstration that administration of 7,8-DHF in the postnatal period P3-P15 restores hippocampal neurogenesis and spinogenesis, we sought to establish whether these effects translate into behavioral benefits after treatment cessation. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) during postnatal days P3-P15 did not show any L&M improvement at one month after treatment cessation, indicating that the effects of 7,8-DHF on the brain are ephemeral. Based on evidence that chronic treatment with 7,8-DHF in juvenile Ts65Dn mice restores L&M, we sought to establish whether a similar effect is elicited in adulthood. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) for about 40 days starting from 4 months of age did not show any improvement in L&M. The results suggest that timing of therapy with 7,8-DHF is a critical issue for attainment of positive effects on the brain. View Full-Text
Keywords: Down syndrome; Ts65Dn mouse; Cognitive impairment; Therapy; Flavonoids; 7,8-dihydroxyflavone; Learning and memory Down syndrome; Ts65Dn mouse; Cognitive impairment; Therapy; Flavonoids; 7,8-dihydroxyflavone; Learning and memory
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Giacomini, A.; Stagni, F.; Emili, M.; Uguagliati, B.; Rimondini, R.; Bartesaghi, R.; Guidi, S. Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse. Antioxidants 2019, 8, 163.

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