Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome

Jared J. Schwartzer*, Dolores Garcia-Arocena, Amanda Jamal, Ali Izadi, Rob Willemsen, Robert F. Berman

*Corresponding author for this work

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Carriers of the fragile X premutation (PM) can develop a variety of early neurological symptoms, including depression, anxiety and cognitive impairment as well as being at risk for developing the late-onset fragile X-associated tremor/ataxia syndrome (FXTAS). The absence of effective treatments for FXTAS underscores the importance of developing efficacious therapies to reduce the neurological symptoms in elderly PM carriers and FXTAS patients. A recent preliminary study reported that weekly infusions of Allopregnanolone (Allop) may improve deficits in executive function, learning and memory in FXTAS patients. Based on this study we examined whether Allop would improve neurological function in the aged CGG knock-in (CGG KI) dutch mouse, B6.129P2(Cg)-Fmr1tm2Cgr/Cgr, that models much of the symptomatology in PM carriers and FXTAS patients. Wild type and CGG KI mice received 10 weekly injections of Allop (10 mg/kg, s.c.), followed by a battery of behavioral tests of motor function, anxiety, and repetitive behavior, and 5-bromo-2′-deoxyuridine (BrdU) labeling to examine adult neurogenesis. The results provided evidence that Allop in CGG KI mice normalized motor performance and reduced thigmotaxis in the open field, normalized repetitive digging behavior in the marble burying test, but did not appear to increase adult neurogenesis in the hippocampus. Considered together, these results support further examination of Allop as a therapeutic strategy in patients with FXTAS.

Original languageEnglish
Article number752973
JournalFrontiers in Neuroscience
Publication statusPublished - 3 Dec 2021

Bibliographical note

Funding Information:
This research was supported by the grant NINDS R01 NS079775 and the UC Davis M.I.N.D. Institute Intellectual and Developmental Disabilities Research Center (IDDRC) grant P50 HD103526.

Publisher Copyright:
Copyright © 2021 Schwartzer, Garcia-Arocena, Jamal, Izadi, Willemsen and Berman.


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