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

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...

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Autores principales:	Jared J. Schwartzer, Dolores Garcia-Arocena, Amanda Jamal, Ali Izadi, Rob Willemsen, Robert F. Berman
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	: FXTAS allopregnanolone mouse behavior adult neurogenesis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/bda62a518b2245d3a407aa50d122b8e5
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spelling	oai:doaj.org-article:bda62a518b2245d3a407aa50d122b8e52021-12-03T06:53:54ZAllopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome1662-453X10.3389/fnins.2021.752973https://doaj.org/article/bda62a518b2245d3a407aa50d122b8e52021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.752973/fullhttps://doaj.org/toc/1662-453XCarriers 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.Jared J. SchwartzerDolores Garcia-ArocenaAmanda JamalAli IzadiRob WillemsenRobert F. BermanRobert F. BermanFrontiers Media S.A.article: FXTASallopregnanolonemousebehavioradult neurogenesisNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	: FXTAS allopregnanolone mouse behavior adult neurogenesis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	: FXTAS allopregnanolone mouse behavior adult neurogenesis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Jared J. Schwartzer Dolores Garcia-Arocena Amanda Jamal Ali Izadi Rob Willemsen Robert F. Berman Robert F. Berman Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome
description	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.
format	article
author	Jared J. Schwartzer Dolores Garcia-Arocena Amanda Jamal Ali Izadi Rob Willemsen Robert F. Berman Robert F. Berman
author_facet	Jared J. Schwartzer Dolores Garcia-Arocena Amanda Jamal Ali Izadi Rob Willemsen Robert F. Berman Robert F. Berman
author_sort	Jared J. Schwartzer
title	Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome
title_short	Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome
title_full	Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome
title_fullStr	Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome
title_full_unstemmed	Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome
title_sort	allopregnanolone improves locomotor activity and arousal in the aged cgg knock-in mouse model of fragile x-associated tremor/ataxia syndrome
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/bda62a518b2245d3a407aa50d122b8e5
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Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome

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