Reversal of ultrasonic vocalization deficits in a mouse model of Fragile X Syndrome with minocycline treatment or genetic reduction of MMP-9.

Reversal of ultrasonic vocalization deficits in a mouse model of Fragile X Syndrome with minocycline treatment or genetic reduction of MMP-9. Behav Brain Res. 2019 Jul 01;:112068 Authors: Toledo MA, Wen TH, Binder DK, Ethell IM, Razak KA Abstract Fragile X Syndrome (FXS) is a leading genetic cause of autism and intellectual disabilities. The Fmr1 knockout (KO) mouse is a commonly studied pre-clinical model of FXS. Adult male Fmr1 KO mice produce fewer ultrasonic vocalizations (USVs) during mating, suggestive of abnormal social communication. Minocycline treatment for 2 months from birth alleviates a number of FXS phenotypes in mice, including USV call rate deficits. In the current study, we investigated if treatment initiated past the early developmental period would be effective, given that in many cases, individuals with FXS are treated during later developmental periods. Wildtype (WT) and Fmr1 KO mice were treated with minocycline between postnatal day (P) 30 and P58. Mating-related USVs were then recorded from these mice between P75 and P90 and analyzed for call rate, duration, bandwidth, and peak frequency. Untreated Fmr1 KO mice call at a significantly reduced rate compared to untreated WT mice. After minocycline treatment from 1-2 months of age, WT and Fmr1 KO mice exhibited similar call rates, due to an increase in calling in the latter group. Minocycline is thought to be effective in reducing FXS symptoms by lowering matrix-...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research