Biomedical subjects

Jessica A Couch

Publications and source records attributed to Jessica A Couch.

3 recordsLinked to original sources

PubMed2007

Intracranial abnormalities detected by three-dimensional magnetic resonance imaging in Prader-Willi syndrome.

The neuropathologic abnormalities associated with Prader-Willi syndrome (PWS) are largely unknown. PWS is due to the loss of several paternally expressed genes in chromosome 15q11-q13 region. Several of the imprinted genes in the 15q11-q13 region are normally expressed in the brain and thought to be necessary for neuronal growth and development. Thus, we hypothesized that we would find abnormalities in gray and white matter growth in individuals with PWS. We evaluated three-dimensional (3-D) MRI scans of 20 individuals with PWS, aged three months to 39 years, and compared them to 3-D MRI scans of 21 normal weight sibling controls and 16 individuals with early-onset morbid obesity (EMO) of unknown etiology. The interpreters of the scans were blinded to the diagnosis of the subjects. Intracranial abnormalities in individuals with PWS included ventriculomegaly (100% of individuals), decreased volume of brain tissue in the parietal-occipital lobe (50%), sylvian fissure polymicrogyria (60%), and incomplete insular closure (65%). None of the EMO or normal weight control subjects had any of these findings. We found multiple morphologic brain abnormalities in subjects with PWS suggesting that the loss of paternally expressed genes in chromosome 15q11-q13 region may result in abnormalities of neuronal development. The specific mechanisms underlying these neuropathological abnormalities and their correlation with the clinical phenotype remain to be elucidated.

Adolescent↗

PubMed2006

Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader-Willi syndrome.

BACKGROUND: Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. METHODS: We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. RESULTS: Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. CONCLUSIONS: Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.

Adult↗

PubMed2004

robo2 and robo3 interact with eagle to regulate serotonergic neuron differentiation.

The function of the central nervous system (CNS) depends crucially upon the correct differentiation of neurons and formation of axonal connections. Some aspects of neuronal differentiation are known to occur as axonal connections are forming. Although serotonin is a highly conserved neurotransmitter that is important for many CNS functions, little is known about the process of serotonergic neuron differentiation. We show that in Drosophila, expression of the serotonin transporter (SerT) is both temporally and physically related to midline crossing. Additionally, we show that the axon guidance molecules roundabout2 and roundabout3 (robo2/3) are necessary for serotonergic neuron differentiation and function independently of their ligand, slit. Loss of robo2 or robo3 causes a loss of SerT expression in about half of neurons, and resembles the phenotype seen in mutants for the transcription factor eagle (eg). Finally, we show a direct relationship between robo2/3 and eg: robo2/3 mutants lose Eg expression in serotonergic neurons, and robo2 and eg interact genetically to regulate SerT expression. We propose that post-midline expression of Robo2/3 is part of a signal that regulates serotonergic neuron differentiation and is transduced by the transcription factor Eg.

Animals↗