Biomedical subjects

Robert Y Moore

Publications and source records attributed to Robert Y Moore.

8 recordsLinked to original sources

PubMed2003

Monoamine neuron innervation of the normal human brain: an 18F-DOPA PET study.

18F-DOPA positron emission tomography (PET) has been used for two decades to study the organization and pathology of the striatal dopamine system in the human brain, particularly in Parkinson's disease. High resolution 3D PET allows a more detailed analysis than previously available and was employed in this study to determine the regional uptake of 18F-DOPA in control brain. Eleven healthy volunteers underwent 18F-DOPA PET with a region of interest (ROI) study performed using individual volumetric MRI's coregistered to the PET ADD image. A Patlak linear graphical analysis was undertaken to obtain influx constant (Ki) values. The highest Ki values were from neostriatal areas, with a rostrocaudal gradient of increasing Ki values from head of caudate nucleus to rostral putamen to caudal putamen. However, Ki values for transaxial slices from dorsal to ventral through the caudate and putamen were uniform. Ventral striatum Ki was 81% with red nucleus and globus pallidus Ki values of approximately 40% of neostriatum. In limbic areas, highest values were obtained from amygdala (35% neostriatal Ki). Neocortical Ki values varied from 22% in temporal pole to 6% in occipital cortex of neostriatal values. Hypothalamic Ki was high (45%) in comparison to thalamus (17%) and retina (17%). 18F-DOPA is taken up by serotonin (raphe, 51%), and noradrenaline (locus coeruleus, 37%) as well as dopamine neurons. These data indicate that 18F-DOPA PET can be used with detailed, anatomically based ROIs as a tool for in vivo analysis of regional changes in monoamine neuron systems throughout the brain in Parkinson's disease and other disorders.

Adult↗

PubMed2003

Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study.

BACKGROUND: Pathology reports have shown that cholinergic forebrain neuronal losses in parkinsonian dementia (PDem) are equal to or greater than those in Alzheimer disease (AD). We hypothesized that patients with PDem would have cholinergic deficits that were similar to or greater than those of patients with AD. OBJECTIVE: To determine in vivo cortical acetylcholinesterase (AChE) activity in healthy control subjects and in patients with mild AD, PDem, and Parkinson disease without dementia using AChE positron emission tomography. SETTING: University and Veterans' Administration medical center. Design and Patients Group comparison design of patients with AD (n = 12), PDem (n = 14), and Parkinson disease without dementia (n = 11), and controls (n = 10) who underwent AChE imaging between July 1, 2000, and January 31, 2003. Patients with AD and PDem had approximately equal dementia severity. MAIN OUTCOME MEASURES: Cerebral AChE activity. RESULTS: Compared with controls, mean cortical AChE activity was lowest in patients with PDem (-20.0%), followed by patients with Parkinson disease without dementia (-12.9%; P<.001). Mean cortical AChE activity was relatively preserved in patients with AD (-9.1%), except for regionally selective involvement of the lateral temporal cortex (-15%; P<.001). CONCLUSION: Reduced cortical AChE activity is more characteristic of patients with PDem than of patients with mild AD.

Acetylcholinesterase↗

PubMed2003

Plasticity of the nigropallidal pathway in Parkinson's disease.

The degeneration of nigrostriatal dopamine neurons in early Parkinson's disease (PD) is compensated in part by increased transmitter turnover in surviving neurons of the pathway. In this (18)F-dopa positron emission tomography study, we demonstrate compensatory changes in PD in another midbrain dopamine projection to the basal ganglia, the nigropallidal projection to the internal segment of the globus pallidus (GPi). Increased (18)F-dopa uptake in the GPi is seen in early PD which then is lost in advanced PD. Our early PD cases show an absence of significant clinical progression in the face of a continuing loss of nigrostriatal projections. This indicates a compensatory neuronal plasticity that we now show to involve the nigropallidal dopamine pathway to the GPi but not to the external segment of the globus pallidus (GPe). Enhanced function of the dopamine projection to the GPi serves, we propose, to maintain a more normal pattern of pallidal output to ventral thalamus and motor cortex in early PD, whereas loss of this adaptive pathway in advanced disease may be a pivotal step in the progression of the disease.

Adult↗

PubMed2003

Organization of midbrain dopamine systems and the pathophysiology of Parkinson's disease.

Understanding of the pathophysiology of Parkinson disease (PD) has advanced rapidly over the last two decades through basic and clinical studies using modern neuroanatomical, clinical assessment, neuropathological and functional brain imaging methods. Two interacting processes determine the development of functional impairment, neuronal degeneration with selective denervation of specific regions and compensatory responses, which oppose the effects of denervation. The clinical manifestations of PD, at least in early stages, reflect selective degeneration of dopamine neurons in the substantia nigra projecting through the nigrostriatal pathway to the caudal putamen with compensatory changes in this and related systems. Positron emission tomography with specific ligands for the dopamine system is a powerful tool for analysis of both degenerative and compensatory processes in the pathophysiology of Parkinson disease in vivo and can be used to confirm the diagnosis of dopamine deficient Parkinson disease.

Dopamine↗

PubMed2003

Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy.

Human narcolepsy is correlated with a greatly reduced number of hypocretin (orexin) containing neurons and axons, and an elevated level of hypothalamic gliosis. We now report that the percentage loss of Hcrt cells and percentage elevation of GFAP staining are variable across forebrain and brain-stem nuclei, and are maximal in the posterior and tuberomammillary hypothalamic region. Regional gliosis and percent loss of hypocretin axons in narcoleptics are not correlated with regional hypocretin cell soma density in normals or with regional percent soma loss in narcoleptics. Rather they are independently and strongly correlated with the regional density of hypocretin axons and the message density for hypocretin receptor 2, as quantified in the rat. These results are consistent with the hypotheses that the loss of hypocretin function in narcolepsy results from a cytotoxic or immunologically mediated attack focused on hypocretin receptor 2 or an antigen anatomically linked to hypocretin receptor 2, and that this process is intensified in regions of high axonal density.

Adult↗

PubMed2002

Suprachiasmatic nucleus organization.

The suprachiasmatic nucleus (SCN) of the hypothalamus is a dominant circadian pacemaker in the mammalian brain controlling the rest-activity cycle and a series of physiological and endocrine functions to provide a foundation for the successful elaboration of adaptive sleep and waking behavior. The SCN is anatomically and functionally organized into two subdivisions: (1) a core that lies adjacent to the optic chiasm, comprises predominantly neurons producing vasoactive intestinal polypeptide (VIP) or gastrin-releasing peptide (GRP) colocalized with GABA and receives dense visual and midbrain raphe afferents, and (2) a shell that surrounds the core, contains a large population of arginine vasopressin (AVP)-producing neurons in its dorsomedial portion, and a smaller population of calretinin (CAR)-producing neurons dorsally and laterally, colocalized with GABA, and receives input from non-visual cortical and subcortical regions. In this paper, we present a detailed quantitative analysis of the organization of the SCN core and shell in the rat and place this in the context of the functional significance of the subdivisions in the circadian control of regulatory systems.

Animals↗

PubMed2002

Paraventricular-subparaventricular hypothalamic lesions selectively affect circadian function.

The circadian timing system has three principal components: (i) entrainment pathways, (ii) pacemakers, and (iii) efferent pathways from the pacemakers that convey the circadian signal to effector systems. The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal mammalian circadian pacemaker and, although we understand the organization of entrainment pathways to the SCN and the pacemaker itself, we know much less about the functional organization of SCN projections mediating control of effector systems. It is unclear, for example, whether specific subsets of SCN projections control specific effector systems. In this study, we analyzed the effects of lesions ablating the paraventricular hypothalamic nucleus (PVH), with variable extension into the subparaventricular zone (SPVZ) and adjacent structures, on nocturnal pineal melatonin production and rhythms in core body temperature (Tb) and rest-activity (R-A). In accordance with prior work, ablation of the PVH abolishes the nocturnal rise in pineal melatonin. Lesions restricted to the PVH do not affect rhythms in Tb and R-A but lesions extending caudally and ventrally into the SPVZ disrupt the R-A rhythm proportionate to the interruption of caudal SCN projections without affecting the rhythm in Tb. We conclude that pacemaker regulation of the circadian rhythms analyzed in this study is mediated by discrete sets of SCN projections: (i) dorsal projections to the PVH control pineal melatonin production; (ii) rostral projections to the anterior hypothalamic/preoptic areas mediate the Tb rhythm; and (iii) caudal projections to the SPVZ and hypothalamic arousal systems located in the posterior and lateral hypothalamic areas control the rhythm in R-A.

Animals↗

PubMed2002

Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking.

Sleep is an essential human function. Although the function of sleep has generally been regarded to be restorative, recent data indicate that it also plays an important role in cognition. The neurobiology of human sleep is most effectively analysed with functional imaging, and PET studies have contributed substantially to our understanding of both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. In this study, PET was used to determine patterns of regional glucose metabolism in NREM sleep compared with waking. We hypothesized that brain structures related to waking cognitive function would show a persistence of function into the NREM sleep state. Fourteen healthy subjects (age range 21-49 years; 10 women, 4 men) underwent concurrent EEG sleep studies and [(18)F]fluoro-2-deoxy-D-glucose PET scans during waking and NREM sleep. Whole-brain glucose metabolism declined significantly from waking to NREM sleep. Relative decreases in regional metabolism from waking to NREM sleep occurred in wide areas of frontal, parietal, temporal and occipital association cortex, primary visual cortex, and in anterior/dorsomedial thalamus. After controlling for the whole-brain declines in absolute metabolism, relative increases in regional metabolism from waking to NREM were found bilaterally in the dorsal pontine tegmentum, hypothalamus, basal forebrain, ventral striatum, anterior cingulate cortex and extensive regions of the mesial temporal lobe, including the amygdala and hippocampus, and in the right dorsal parietal association cortex and primary somatosensory and motor cortices. The reductions in relative metabolism in NREM sleep compared with waking are consistent with prior findings from blood flow studies. The relative increases in glucose utilization in the basal forebrain, hypothalamus, ventral striatum, amygdala, hippocampus and pontine reticular formation are new observations that are in accordance with the view that NREM sleep is important to brain plasticity in homeostatic regulation and mnemonic processing.

Adult↗