scholarly journals Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter geneSlc6a8

2018 ◽  
Vol 17 (6) ◽  
pp. e12461 ◽  
Author(s):  
K. C. Udobi ◽  
A. N. Kokenge ◽  
E. R. Hautman ◽  
G. Ullio ◽  
J. Coene ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Creatine Transporter

scholarly journals Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Francesco Cacciante ◽  
Mariangela Gennaro ◽  
Giulia Sagona ◽  
Raffaele Mazziotti ◽  
Leonardo Lupori ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Therapeutic Benefit ◽  
Behavioral Disturbances ◽  
Creatine Transporter ◽  
Chemically Modified ◽  
Eeg Abnormalities ◽  
Creatine Transporter Deficiency ◽  
Novel Biomarkers ◽  
Transporter Deficiency ◽  
Potential Therapeutic Benefit

Abstract Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr.

scholarly journals Deletion of the creatine transporter gene in neonatal, but not adult, mice leads to cognitive deficits

2019 ◽  
Vol 42 (5) ◽  
pp. 966-974 ◽  
Author(s):  
Kenea C. Udobi ◽  
Nicholas Delcimmuto ◽  
Amanda N. Kokenge ◽  
Zuhair I. Abdulla ◽  
Marla K. Perna ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Transporter Gene ◽  
Creatine Transporter ◽  
Adult Mice

scholarly journals Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter gene Slc6a8

2017 ◽  
Author(s):  
Kenea C. Udobi ◽  
Amanda N. Kokenge ◽  
Emily R. Hautman ◽  
Gabriela Ullo ◽  
Julie Coene ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Water Maze ◽  
Memory Deficits ◽  
Whole Body ◽  
Novel Object Recognition ◽  
Transporter Gene ◽  
Biochemical Phenotype ◽  
Creatine Transporter ◽  
Novel Object ◽  
Path Lengths

AbstractCreatine transporter (CrT; SLC6A8) deficiency (CTD) is an X-linked disorder characterized by severe cognitive deficits, impairments in language, and an absence of brain creatine (Cr). In a previous study, we generated floxed Slc6a8 (Slc6a8flox) mice to create ubiquitous Slc6a8 knockout (Slc6a8-/y) mice. Slc6a8-/y mice lacked whole body Cr and exhibited cognitive deficits. While Slc6a8-/y mice have a similar biochemical phenotype to CTD patients, they also showed a reduction in size and reductions in swim speed that may have contributed to the observed deficits. To address this, we created brain-specific Slc6a8 knockout (bKO) mice by crossing Slc6a8Flox mice with Nestin-cre mice. bKO mice had reduced cerebral Cr levels while maintaining normal Cr levels in peripheral tissue. Interestingly, brain concentrations of the Cr synthesis precursor guanidinoacetic acid were increased in bKO mice. bKO mice had longer latencies and path lengths in the Morris water maze, without reductions in swim speed. In accordance with data from Slc6a8-/y mice, bKO mice showed deficits in novel object recognition as well as contextual and cued fear conditioning. bKO mice were also hyperactive, in contrast with data from the Slc6a8-/ymice. The results demonstrate that the loss of cerebral Cr is responsible for the learning and memory deficits seen in ubiquitous Slc6a8-/y mice.

scholarly journals Female mice heterozygous for creatine transporter deficiency show moderate cognitive deficits

2013 ◽  
Vol 37 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Emily R. Hautman ◽  
Amanda N. Kokenge ◽  
Kenea C. Udobi ◽  
Michael T. Williams ◽  
Charles V. Vorhees ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Creatine Transporter ◽  
Female Mice ◽  
Creatine Transporter Deficiency ◽  
Transporter Deficiency

scholarly journals Deletion of the creatine transporter gene in neonatal, but not adult, mice lead to cognitive deficits

2019 ◽  
Author(s):  
Kenea C. Udobi ◽  
Nicholas Delcimmuto ◽  
Amanda N. Kokenge ◽  
Zuhair I. Abdulla ◽  
Marla K. Perna ◽  
...  
Keyword(s):  
Brain Development ◽  
Cognitive Deficits ◽  
Knockout Mice ◽  
Language Impairment ◽  
Dark Phase ◽  
Creatine Transporter ◽  
Adult Mice ◽  
Object Learning ◽  
Critical Areas ◽  
Severe Intellectual Disability

AbstractCreatine (Cr) is a guanidino compound that provides readily-available phosphate pools for the regeneration of spent ATP. The lack of brain Cr causes moderate to severe intellectual disability, language impairment, and epilepsy. The most prevalent cause of Cr deficiency are mutations in the X-linkedSLC6A8(Creatine transporter; CrT) gene, known as CrT deficiency (CTD). There are no current treatments for CTD and the mechanisms that underlie the cognitive deficits are poorly understood. One of the most critical areas that need to be addressed is if Cr is necessary for brain development. To address this concern, theSlc6a8gene was knocked out in either neonatal (postnatal day (P)5) or adult (P60) mice. The P5 knockout mice showed deficits in the Morris water maze and novel object recognition, while there were no deficits in P60 knockout mice. Interestingly, the P5 knockout mice showed hyperactivity during the dark phase; however, when examining control mice, the effect was due to the administration of tamoxifen from P5-10. Taken together, the results of this study show that Cr is necessary during periods of brain development involved in spatial and object learning. This study also highlights the continued importance of using proper control groups for behavioral testing.Take-home messageThe learning and memory deficits seen in Slc6a8-deficient mice are likely due to the developmental loss of Cr.

No Cognitive Deficits in Preeclamptics on MgSO4

Ob Gyn News ◽  
2005 ◽  
Vol 40 (2) ◽  
pp. 20
Author(s):  
MIRIAM E. TUCKER
Keyword(s):  
Cognitive Deficits

Topographische Orientierung bei Patienten mit erworbener Hirnschädigung

1999 ◽  
Vol 10 (2) ◽  
pp. 77-86
Author(s):  
Martina Kindsmüller ◽  
Andrea Kaindl ◽  
Uwe Schuri ◽  
Alf Zimmer
Keyword(s):  
Brain Damage ◽  
Cognitive Deficits ◽  
Hospital Setting ◽  
Hospital Staff ◽  
Reading Test ◽  
Map Reading ◽  
Several Variables ◽  
Topographical Orientation ◽  
The One ◽  
Behavioral Memory

Topographical Orientation in Patients with Acquired Brain Damage Abstract: A study was conducted to investigate the abilities of topographical orientation in patients with acquired brain damage. The first study investigates the correlation between wayfinding in a hospital setting and various sensory and cognitive deficits as well as the predictability of navigating performance by specific tests, self-rating of orientation ability and rating by staff. The investigation included 35 neuropsychological patients as well as 9 control subjects. Several variables predicted the wayfinding performance reasonably well: memory tests like the one introduced by Muramoto and a subtest of the Rivermead Behavioral Memory Test, the Map Reading Test and the rating by hospital staff. Patients with hemianopia experienced significant difficulty in the task.

Morphological Changes in the Brain of Acutely Ill and Weight-Recovered Patients with Anorexia Nervosa

2014 ◽  
Vol 42 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Jochen Seitz ◽  
Katharina Bühren ◽  
Georg G. von Polier ◽  
Nicole Heussen ◽  
Beate Herpertz-Dahlmann ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Cognitive Deficits ◽  
Time Course ◽  
Morphological Changes ◽  
Meta Analysis ◽  
Short Term ◽  
Clinical Prognosis ◽  
Qualitative Review ◽  
Brain Changes ◽  
The Brain

Objective: Acute anorexia nervosa (AN) leads to reduced gray (GM) and white matter (WM) volume in the brain, which however improves again upon restoration of weight. Yet little is known about the extent and clinical correlates of these brain changes, nor do we know much about the time-course and completeness of their recovery. Methods: We conducted a meta-analysis and a qualitative review of all magnetic resonance imaging studies involving volume analyses of the brain in both acute and recovered AN. Results: We identified structural neuroimaging studies with a total of 214 acute AN patients and 177 weight-recovered AN patients. In acute AN, GM was reduced by 5.6% and WM by 3.8% compared to healthy controls (HC). Short-term weight recovery 2–5 months after admission resulted in restitution of about half of the GM aberrations and almost full WM recovery. After 2–8 years of remission GM and WM were nearly normalized, and differences to HC (GM: –1.0%, WM: –0.7%) were no longer significant, although small residual changes could not be ruled out. In the qualitative review some studies found GM volume loss to be associated with cognitive deficits and clinical prognosis. Conclusions: GM and WM were strongly reduced in acute AN. The completeness of brain volume rehabilitation remained equivocal.

Sign in / Sign up

Export Citation Format

Share Document