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

• DOI: 10.3389/fnins.2021.752973
• Publication Date: 2021-12-03T06:54:26Z
• Authors: Jared J. Schwartzer; Dolores Garcia-Ar...; Amanda Jamal; Ali Izadi; Rob Willemsen; Robert F. Berman
• Keywords: Allopregnanolone; Gene knockin

Carriers of the fragile X premutation (PM) can develop a variety early neurological symptoms, including depression, anxiety and cognitive impairment as well being at risk for developing late-onset X-associated tremor/ataxia syndrome (FXTAS). The absence effective treatments FXTAS underscores importance efficacious therapies to reduce symptoms in elderly PM carriers patients. A recent preliminary study reported that weekly infusions Allopregnanolone (Allop) may improve deficits executive function, learning memory Based on this we examined whether Allop would function aged CGG knock-in (CGG KI) dutch mouse, B6.129P2(Cg)-Fmr1 tm2Cgr /Cgr, models much symptomatology Wild type KI mice received 10 injections (10 mg/kg, s.c.), followed by battery behavioral tests motor anxiety, repetitive behavior, 5-bromo-2′-deoxyuridine (BrdU) labeling examine adult neurogenesis. results provided evidence normalized performance reduced thigmotaxis open field, digging behavior marble burying test, but did not appear increase neurogenesis hippocampus. Considered together, these support further examination therapeutic strategy patients with FXTAS.