Gabrb3 gene deficient mice exhibit increased risk assessment behavior, hypotonia and expansion of the plexus of locus coeruleus dendrites

Hashemi, Ezzat; Sahbaie, Peyman; Davies, M. Frances; Clark, J. David; DeLorey, Timothy M.

doi:10.1016/j.brainres.2006.10.050

Cited by 28 publications

(22 citation statements)

References 66 publications

(82 reference statements)

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“…We observed no gender difference in the number of marbles buried by male or female control mice as has also been reported elsewhere [26, 46]. Significant genotype differences in marble burying behavior was observed amongst female mouse variants (F 2,41 =4.86, p <0.05) with post hoc tests revealing female p−/m+ mice, but not p+/m− mice, to be significantly different from female controls ( p <0.01).…”

Section: Resultssupporting

confidence: 90%

“…Previous studies utilizing the V1aR gene knockout mouse [13] and the Gabrb3 gene knockout mouse [26], both models of ASD, reported reductions in marble burying behavior. In the current study, male and female p−/m+ mice also displayed reduced marble burying behavior while their p+/m− counterparts did not (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…The above findings appear to be counterintuitive as one would have predicted that an autism model would exhibit more preservative behavior, not less, leading to an increase in marbles buried. We considered whether tactile hypersensitivity or hypotonia, both observed in Gabrb3 knockout mice [26, 65], might account for reduced digging in p−/m+ mice. However, no evidence for hypotonia, as assessed by the wire-hanging task, was observed in any heterozygote and no association between tactile hypersensitivity and the number of marble buried was apparent.…”

Section: Discussionmentioning

confidence: 99%

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Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3

DeLorey

Sahbaie

Hashemi

et al. 2011

Behavioural Brain Research

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Autism spectrum disorder (ASD) is diagnosed based on three core features: impaired social interactions, deficits in communication and repetitive or restricted behavioral patterns. Against this backdrop, abnormal sensory processing receives little attention despite its prevalence and the impact it exerts on the core diagnostic features. Understanding the source of these sensory abnormalities is paramount to developing intervention strategies aimed at maximizing the coping ability of those with ASD. Consequently, we chose to examine whether sensory abnormalities were present in mice heterozygous for the Gabrb3 gene, a gene strongly associated with ASD. Mice were assessed for tactile and heat sensitivity, sensorimotor competence (accelerating rotarod task) and sensorimotor gating by prepulse inhibition of the acoustic startle reflex (PPI). All heterozygotes exhibited an increase in seizure susceptibility and similar reductions in Gabrb3 expression in the dorsal root ganglia, spinal cord, whole brain and amygdala. Interestingly, significant differences were noted between heterozygous variants in regards to tactile sensitivity, heat sensitivity, sensorimotor competence and PPI along with differences in Gabrb3 expression in the reticular thalamic nucleus and the bed nucleus of stria terminalis. These differences were influenced by the heterozygotes’ gender and whether the Gabrb3 gene was of paternal or maternal origin. These results are not adequately explained by simple haploinsufficiency of Gabrb3, therefore, additional mechanisms are likely to be involved. In addition, this is the first report of the occurrence of tactile and heat hypersensitivity in an ASD mouse model, two features often associated with ASD.

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Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3

DeLorey

Sahbaie

Hashemi

et al. 2011

Behavioural Brain Research

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“…In some diseases, the muscle strength is the parameter that characterizes the state of development of the illness and several tests have been developed for their knowledge. For this purpose, a variety of tests like rotarod test, hanging wire test, open field or walking pattern test [3][4][5] have been developed. However, these tests need the training of the animal and they have a certain grade of subjectivity.…”

Section: Introductionmentioning

confidence: 99%

Force plate for measuring small animal forces by digital speckle pattern interferometry

et al. 2007

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This paper presents a force plate specially designed for measuring ground reaction forces in small animals. Digital Speckle Pattern Interferometry (DSPI) is used to measure the plate deformation produced by the animal. Elasticity theory is used to obtain force magnitude and application position from the vertical displacement field measured with DSPI. The force plate has been tested with static weights of 5 g and 10 g at various locations on the plate. Some experiments with 20 g body weight transgenic mice are also reported.

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“…GABA receptors are expressed in central nervous system, testes, heart, lungs, pancreas, intestine, kidneys and adrenal glands. Mice with GABA receptor β3 gene deficiency suffer from hypotonia and neuro-behavioural problems similar to PWS (Hashemi, Sahbaie et al 2007). Using [ higher plasma GABA level in PWS (Ebert, Schmidt et al 1997).…”

Section: 7: Discussionmentioning

confidence: 99%

Energy Homeostasis in children with Prader- Willi syndrome

Nyunt¹

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IntroductionPrader-Willi syndrome (PWS) is a genetic condition commonly associated with hyperphagia and obesity. PWS is thought to have hypothalamic dysfunction which is the head ganglion of autonomic nervous system (ANS). In current literature, ANS is believed to be defective in PWS. ANS may also have a role in controlling orexigenic hormone ghrelin and energy expenditure. One study reported higher resting energy expenditure adjusted for lean body mass in growth hormone naive PWS group but another study found lower activity associated energy expenditure compared to controls. Other studies found adjusted basal and sleeping metabolic rates were not different to the controls. Complete profile of energy expenditure in PWS remains unclear.We hypothesize that there is defective ANS in PWS, as a result of hypothalamus dysfunction, and it leads to high orexigenic hormone, acyl ghrelin, and low energy expenditure that in turn cause obesity. MethodsWe compared the ANS functions, acyl ghrelin status and energy expenditure in children with PWS and controls.We recruited 16 genetically-confirmed children with PWS and 16 controls. Exclusion criteria were diabetes mellitus, psycho-trophic medications, and other hypothalamic pathologies.We performed a mixed meal challenge to assess ANS function and acyl ghrelin status of PWS and control groups. We used Bodystat 1500 ® to measure body composition.Orthostatic hypotension, due to gravity, stimulates baroreceptors and activates sympathetic nervous system to counter regulate postural drop in blood pressure by increasing pulse rate, stroke volume and vasoconstriction. We used orthostatic change in pulse rate (PR), blood pressure (BP), and mean arterial pressure (MAP) expressed as per cent change of PR (%ΔPR), BP (%ΔBP), and MAP (%ΔMAP) from lying to standing to access sympathetic nervous function. ANS was further stimulated by a mixed meal and we examined %ΔPR, %ΔBP, and %ΔMAP at 15 and 30 seconds after standing from recumbent position; at fasting, and post-prandial periods. We also measured plasma gastrin, catecholamines (Pcat) and urinary catecholamines (Ucat) at fasting and postprandial periods to complement autonomic cardiovascular data. Using Actiheart®, we compared weight and fat free mass adjusted total, resting, activity-associated and nonexercise associated thermogenesis between two groups. 3 ResultsPWS group was younger, shorter, and had reduced lean mass than the controls. Postprandial %ΔPR at both 15 and 30 seconds were significantly lower in PWS group than controls. The difference in %Δ systolic BP and diastolic BP did not reach statistical significance but %ΔMAP at 60 min and 120 min after meal was significantly lower in PWS.Postprandial plasma gastrin and Ucat were higher in PWS group than controls but Pcat were not different in two groups. Fasting plasma acyl ghrelin (AG) was significantly higher in PWS but it decreased to similar level of controls at 60 and 120 minutes after a meal.The rate of fall of plasma acyl ghrelin was faster in the PWS group than the ...

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Gabrb3 gene deficient mice exhibit increased risk assessment behavior, hypotonia and expansion of the plexus of locus coeruleus dendrites

Cited by 28 publications

References 66 publications

Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3

Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3

Force plate for measuring small animal forces by digital speckle pattern interferometry

Energy Homeostasis in children with Prader- Willi syndrome

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