Role of an enriched environment on the restoration of behavioral deficits in Lurcher mutant mice

Caston, J.; Devulder, B.; Jouen, F.; Lalonde, Robert; Delhaye‐Bouchaud, Nicole; Mariani, Jean

doi:10.1002/(sici)1098-2302(199912)35:4<291::aid-dev4>3.0.co;2-u

Cited by 49 publications

(28 citation statements)

References 57 publications

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“…Trunk curl was assessed by suspending the mouse by the tail. Neuromuscular strength and stamina were tested using the wire hang test (e.g., Caston et al 1999;Gerlai et al 2000). For this test, the mouse gripped onto ‫ف‬ 5 mm round metal bars.…”

Section: Initial Evaluationmentioning

confidence: 99%

Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Holmes

Yang

Murphy

et al. 2002

Neuropsychopharmacology

262

181

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Inhibition of the serotonin transporter (5-HTT) is a principal initial target of many antidepressants. However, the contribution of the 5-HTT to their therapeutic efficacy is incompletely understood. We utilized a targeted gene mutation approach to examine the role of the 5-HTT in the behavioral actions of antidepressants. The 5-HTT mutation was bred onto two separate genetic backgrounds, C57BL/6J and 129S6. On a preliminary screen for gross physical, neurological and behavioral functions, all measures were normal with the exception that 5-HTT 5-HTT Ϫ / Ϫ mice on the C57BL/6J background showed no baseline antidepressant-related phenotype on either test. The behavioral effects of three antidepressants were tested in 5-HTT mutant mice (C57BL/6J background) in the tail suspension test. The anti-immobility effects of the serotonin reuptake inhibitor, fluoxetine (30 mg/kg), were abolished in 5-HTT Ϫ / Ϫ mice, confirming that the 5-HTT gene is required for the behavioral effects of fluoxetine. In contrast, 5-HTT Ϫ / Ϫ mice retained sensitivity to the anti-immobility effects of the norepinephrine reuptake inhibitor, desipramine (20 mg/kg), and the mixed serotonin/norepinephrine reuptake inhibitor, imipramine (25 mg/kg Antidepressants are thought to normalize the disturbances in monoamine function that occur in affective disorders (Feighner and Boyer 1996;Frazer 1997; Montgomery and Den Boer 2001). While dysfunctions in noradrenergic and dopaminergic systems are putative etiological factors in depression, there is considerable evidence indicating that perturbation of central serotonergic activity is a major etiological component of depression (Willner 1985;Murphy 1990;Maes and Meltzer 1995;Charney 1998 NO . 6 Antidepressant Responses in 5-HTT KO Mice 915 (for reviews see Brown and Linnoila 1990;Owens and Nemeroff 1998;Mann 1999). The serotonin transporter (5-HTT) acts as a key regulator of serotonin signaling. By regulating reuptake of released serotonin, the 5-HTT controls the duration and intensity of serotoninergic activity at the synapse. The 5-HTT has been directly implicated in depression by the finding that brain 5-HTT binding density is reduced in brains and platelets of depressed patients (e.g., Nemeroff et al. 1994;Malison et al. 1998;Mann et al. 2000). Moreover, a number of studies have found an association between genetic variation in the regulatory region of the 5-HTT gene and depression (e.g., Battersby et al. 1996; Collier et al. 1996a,b;Furlong et al. 1998;Rees et al. 1997;Menza et al. 1999; but see Seretti et al. 1999). The 5-HTT is also a major target for many antidepressant drug treatments (Blakely et al. 1991;Ramamoorthy et al. 1993). It is well known that the serotonin reuptake inhibitor (SRI) class of antidepressants increase concentrations of serotonin in the synapse by blocking the serotonin transporter (5-HTT) (Blakely et al. 1991;Ramamoorthy et al. 1993). However, given the time lag between the initial inhibitory effects of antidepressants on the 5-HTT and an observable improvement in sympt...

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Section: Initial Evaluationmentioning

confidence: 99%

Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Holmes

Yang

Murphy

et al. 2002

Neuropsychopharmacology

262

181

View full text Add to dashboard Cite

show abstract

“…The basic motoric abilities measured were: the maintenance of positional passivity when placed on a 451-inclined Plexiglas sheet, forepaw reaching when slowly lowered to a solid surface; trunk curl when suspended by the tail; righting reflex when placed in the supine position. Neuromuscular strength and stamina were tested using the wire hang test (eg Caston et al, 1999;Gerlai et al, 2000). For this test, the mouse gripped onto B5 mm gauge round metal bars.…”

Section: Open Field Testmentioning

confidence: 99%

Galanin GAL-R1 Receptor Null Mutant Mice Display Increased Anxiety-Like Behavior Specific to the Elevated Plus-Maze

Holmes

Kinney

Wrenn

et al. 2003

Neuropsychopharmacol

189

137

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The neuropeptide galanin coexists with norepinephrine and serotonin in neural systems mediating emotion. Previous findings suggested that galanin modulates anxiety-related behaviors in rodents. Three galanin receptor subtypes have been cloned; however, understanding their functions has been limited by the lack of galanin receptor subtype-selective ligands. To study the role of the galanin GAL-R1 receptor subtype in mediating anxiety-related behavior, we generated mice with a null mutation in the Galr1 gene. GAL-R1 À/À are viable and show no abnormalities in health, neurological reflexes, motoric functions, or sensory abilities. On a battery of tests for anxietylike behavior, GAL-R1 À/À showed increased anxiety-like behavior on the elevated plus-maze test. Anxiety-related behaviors on the light/dark exploration, emergence, and open field tests were normal in GAL-R1 À/À. This test-specific anxiety-like phenotype was confirmed in a second, independent cohort of GAL-R1 null mutant mice and +/+ controls. Principal components factor analysis of behavioral scores from 279 mice suggested that anxiety-like behavior on the elevated plus-maze was qualitatively distinct from behavior on other tests in the battery. In addition, exposure to the elevated plus-maze produced a significantly greater neuroendocrine response than exposure to the light/dark exploration test, as analyzed in normal C57BL/6J mice. These behavioral findings in the first galanin receptor null mutant mouse are consistent with the hypothesis that galanin exerts anxiolytic actions via the GAL-R1 receptor under conditions of relatively high stress.

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“…Mice with a mutation in the delta-2 glutamate receptor gene (lurcher mutants) show enhanced survival and improved behavioral function in an enriched environment (Caston et al 1999). The Atm −/− mice also showed enhanced (albeit not to wild-type levels) sur-vival of neurons in response to running.…”

Section: Genes and Development 559mentioning

confidence: 99%

Ataxia telangiectasia mutated is essential during adult neurogenesis

Allen¹,

Praag²,

Ray³

et al. 2001

Genes Dev.

149

118

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Ataxia telangiectasia (A-T) is an autosomal recessive disease characterized by normal brain development followed by progressive neurodegeneration. The gene mutated in A-T (ATM) is a serine protein kinase implicated in cell cycle regulation and DNA repair. The role of ATM in the brain and the consequences of its loss on neuronal survival remain unclear. We studied the role of ATM in adult neural progenitor cells in vivo and in vitro to define the role of ATM in dividing and postmitotic neural cells from Atm-deficient (Atm −/− ) mice in a physiologic context. We demonstrate that ATM is an abundant protein in dividing neural progenitor cells but is markedly down-regulated as cells differentiate. In the absence of ATM, neural progenitor cells of the dentate gyrus show abnormally high rates of proliferation and genomic instability. Atm −/− cells in vivo, and in cell culture, show a blunted response to environmental stimuli that promote neural progenitor cell proliferation, survival, and differentiation along a neuronal lineage. This study defines a role for ATM during the process of neurogenesis, demonstrates that ATM is required for normal cell fate determination and neuronal survival both in vitro and in vivo, and points to a mechanism for neuronal cell loss in progressive neurodegenerative diseases.

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Role of an enriched environment on the restoration of behavioral deficits in Lurcher mutant mice

Cited by 49 publications

References 57 publications

Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Galanin GAL-R1 Receptor Null Mutant Mice Display Increased Anxiety-Like Behavior Specific to the Elevated Plus-Maze

Ataxia telangiectasia mutated is essential during adult neurogenesis

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