Lack of Tryptophan Hydroxylase-1 in Mice Results in Gait Abnormalities

Suidan, Georgette L.; Duerschmied, Daniel; Dillon, Gregory M.; VanderHorst, Veronique; Hampton, Thomas G.; Wong, Siu Ling; Voorhees, Jaymie R.

doi:10.1371/journal.pone.0059032

Cited by 18 publications

(13 citation statements)

References 43 publications

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“…However, Tryptophan hydroxylase-1 (TPH1) is only expressed by non-neuronal cells including enterochromaffin cells of gut, mast cells, and pineal gland, and it has not been found to have any differences between the Tph1deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field, and beam walk. 18 KIAA1024 located in 15q25.1 presents more than 350 missense variants in ExAC database including several in the same region (p.(R608Q), p.(S614L), p.(R617C)). Finally, MADD, a splice variant of IG20 gene, encodes a protein highly expressed in melanocytes, parotid acinar cells, and involved in physiological cell death.…”

Section: Discussionmentioning

confidence: 99%

Loss of Function of KCNC1 is associated with intellectual disability without seizures

et al. 2017

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p.(Arg320His) mutation in the KCNC1 gene in human 11p15.1 has recently been identified in patients with progressive myoclonus epilepsies, a group of rare inherited disorders manifesting with action myoclonus, myoclonic epilepsy, and ataxia. This KCNC1 variant causes a dominant-negative effect. Here we describe three patients from the same family with intellectual disability and dysmorphic features. The three affected individuals carry a c.1015C>T (p.(Arg339*)) nonsense variant in KCNC1 gene. As previously observed in the mutant mouse carrying a disrupted KCNC1 gene, these findings reveal that individuals with a KCNC1 loss-of-function variant can present intellectual disability without seizure and epilepsy.

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Section: Discussionmentioning

confidence: 99%

Loss of Function of KCNC1 is associated with intellectual disability without seizures

et al. 2017

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“…Challenging Beam Traversal Test, Pole test (Fleming et al 2006;Schintu et al 2009), Grid test (Sgado et al 2011;Tillerson and Miller 2003), beam walk test (Suidan et al 2013) were performed as described earlier in order to evaluate motor deficits.…”

Section: Behavioral Assessmentsmentioning

confidence: 99%

Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of α-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study

et al. 2015

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Evidence suggests that accumulation and aggregation of α-synuclein contribute to the pathogenesis of Parkinson's disease (PD). The aim of this study was to evaluate whether diffusion kurtosis imaging (DKI) will provide a sensitive tool for differentiating between α-synuclein-overexpressing transgenic mouse model of PD (TNWT-61) and wild-type (WT) littermates. This experiment was designed as a proof-of-concept study and forms a part of a complex protocol and ongoing translational research. Nine-month-old TNWT-61 mice and age-matched WT littermates underwent behavioral tests to monitor motor impairment and MRI scanning using 9.4 Tesla system in vivo. Tract-based spatial statistics (TBSS) and the DKI protocol were used to compare the whole brain white matter of TNWT-61 and WT mice. In addition, region of interest (ROI) analysis was performed in gray matter regions such as substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus known to show higher accumulation of α-synuclein. For the ROI analysis, both DKI (6 b-values) protocol and conventional (2 b-values) diffusion tensor imaging (cDTI) protocol were used. TNWT-61 mice showed significant impairment of motor coordination. With the DKI protocol, mean, axial, and radial kurtosis were found to be significantly elevated, whereas mean and radial diffusivity were decreased in the TNWT-61 group compared to that in the WT controls with both TBSS and ROI analysis. With the cDTI protocol, the ROI analysis showed decrease in all diffusivity parameters in TNWT-61 mice. The current study provides evidence that DKI by providing both kurtosis and diffusivity parameters gives unique information that is complementary to cDTI for in vivo detection of pathological changes that underlie PD-like symptomatology in TNWT-61 mouse model of PD. This result is a crucial step in search for a candidate diagnostic biomarker with translational potential and relevance for human studies.

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“…In addition, 5-HT is implicated in the emergence of many neuropsychiatric disorders, including mental retardation, autism, depression and anxiety [10,15,[21][22][23][24][25][26]. Importantly, 5-HT signalling is influenced by numerous epigenetic and genetic factors, including nutrition and gut microbiota [27,28], perinatal stress [29][30][31], infection and inflammation [32][33][34][35], 5-HT metabolism and storage [15,[36][37][38], pharmacological compounds such as selective serotonin reuptake inhibitors [38][39][40] and genetic alterations [41][42][43][44].…”

Section: Introductionmentioning

confidence: 99%

Sculpting Cerebral Cortex with Serotonin in Rodent and Primate

Vitalis¹,

Verney²

2017

Serotonin - A Chemical Messenger Between All Types of Living Cells

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The mammalian cerebral cortex is critical for sensory and motor integrations and, for higher-order cognitive functions. The construction of mammalian cortical circuits involves the coordinated interplay between cellular processes such as proliferation, migration and differentiation of neural and glial cell subtypes followed by accurate connectivity evolving in complexity in primates. Alteration in cortical development may induce the emergence of various pathological traits and behaviours. Among the large array of factors that regulate the assembly of cortical circuits, serotonin (5-HT) plays important role as a developmental signal that impacts on a broad diversity of cellular processes. 5-HT plays distinct roles during specific sensitive periods and is produced from various sources depending on the perinatal stage. Its roles are mediated by more than fourteen 5-HT receptors that are all G-protein coupled receptors except the ionotropic 5-HT type 3A receptor (5-HT 3A ) mediating rapid neuronal activation. Importantly, 5-HT metabolism and signalling are influenced by numerous epigenetic and genetic factors, including nutrition and gut microbiota, perinatal stress, infection and inflammation. In this review, we will recapitulate some evidences showing that dysregulation of 5-HT homeostasis and 5-HT 3A signalling impairs distinct steps of cortical circuit formation leading to the predisposition of the onset of various psychiatric diseases.

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Lack of Tryptophan Hydroxylase-1 in Mice Results in Gait Abnormalities

Cited by 18 publications

References 43 publications

Loss of Function of KCNC1 is associated with intellectual disability without seizures

Loss of Function of KCNC1 is associated with intellectual disability without seizures

Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of α-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study

Sculpting Cerebral Cortex with Serotonin in Rodent and Primate

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