Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have documented a highly compartmentalized and laminar organization of dopamine D2 receptors in human hippocampus, entorhinal and perirhinal cortices. These areas receive input from regions of polysensory association cortices of the superior and inferior temporal sulci that evidence functional modules identified by other techniques. We examined the isocortical regions of temporal lobe for an equally well-differentiated pattern of D2 receptor expression as observed in their paleocortical temporal lobe targets. Using quantitative autoradiography we identified an organization of three-dimensional bands of high concentrations of dopamine D2 receptors throughout the rostral-caudal extent of the normal human temporal cortex. In the coronal plane, these D2 receptor-enriched bands had a columnar appearance with the concentration of D2 receptors almost two-fold higher within the bands than in the immediately adjacent cortex. These D2 receptor-enriched bands had a distinct laminar appearance with a paucity of [125I]epidepride binding to D2 receptors over the granule cell layer and higher concentrations of D2 receptors in laminae III and V than in the immediately adjacent cortex. They had a consistent width (mean width of 2.83 +/- 0.62 mm) in the coronal plane, but had their long axes in the rostrocaudal plane (some were at least 2500 microns in length). Hence, they exist as three-dimensional D2 receptor-enriched and receptor-poor modules with their long axes in the rostrocaudal plane. Tyrosine hydroxylase-immunoreactive fibers were observed to cross orthogonally to the long axes of the D2 receptor enriched bands. Other monoamine receptors (beta-adrenergic, 5-hydroxytryptamine2), and markers for myelin (anti-myelin basic protein immunohistochemistry), glia (5'-nucleotidase), and energy metabolism (cytochrome oxidase) showed a laminar organization but failed to demarcate the D2 receptor-enriched bands. The majority of these D2 receptor-enriched bands were observed in the lateral and inferior aspects of the superior temporal gyrus, less frequently on the lateral surface of the inferior temporal gyrus and the parahippocampal cortices (Brodmann's area 22, 42 and 20, 21, 37). They were absent from primary auditory cortex (Brodmann's 41). The present study is the first known observation of a modular organization of synaptic elements, identified by D2 receptors, in non-primary sensory cortices of any species. The dopamine D2 receptor-enriched bands were found in regions previously identified as having functional modules that underlie feature extraction. Hence, D2 receptor-enriched and receptor-poor modules may provide a mechanism for functional regulation of compartments within these regions by dopamine.
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PMID:Dopamine D2 receptors are organized in bands in normal human temporal cortex. 886 95

In a recent study, we demonstrated that cytochrome-c oxidase (COX), an indicator of neuronal activity, is increased in several brain regions from chronic, medicated schizophrenics. In the present study, to address the functional significance of those findings, we have measured COX activity in a group of schizophrenics in whom antemortem geriatric measures of motor, intellectual, and emotional impairment had been assessed. COX activity in the putamen was strongly negatively correlated with emotional (r = -.76; p < .005) and intellectual impairment (r = -0.76; p < .005), but not with motor impairment (r = 0.01). No significant correlations could be found in the frontal cortex, thalamus, caudate nucleus, globus pallidus, mesencephalon, or nucleus accumbens. Dopamine D2 receptor density in the putamen, measured with [3H]raclopride, was elevated in schizophrenics as compared to controls, as were Kd values. In contrast to COX activity, D2 receptor binding was moderately, but significantly positively correlated with intellectual impairment (r = 0.64; p < .05) but not with motor impairment. Results expose a unique anomaly in the effects of neuroleptics in terms of increasing neuronal signaling in the putamen, which may underlie a reversal of cognitive deficits in schizophrenics, while at the same time, elevating D2 receptor density that seems to be detrimental.
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PMID:Putamen mitochondrial energy metabolism is highly correlated to emotional and intellectual impairment in schizophrenics. 1069 56

Repetitive behaviors (e.g., stereotypic movements, compulsions, rituals) are common features of a number of neurodevelopmental disorders. Clinical and animal model studies point to the importance of cortical-basal ganglia circuitry in the mediation of repetitive behaviors. In the current study, we tested whether a drug cocktail (dopamine D2 receptor antagonist + adenosine A2A receptor agonist + glutamate mGlu5 positive allosteric modulator) designed to activate the indirect basal ganglia pathway would reduce repetitive behavior in C58 mice after both acute and sub-chronic administration. In addition, we hypothesized that sub-chronic administration (i.e. 7 days of twice-daily injections) would increase the functional activation of the subthalamic nucleus (STN), a key node of the indirect pathway. Functional activation of STN was indexed by dendritic spine density, analysis of GABA, glutamate, and synaptic plasticity genes, and cytochrome oxidase activity. The drug cocktail used significantly reduced repetitive motor behavior in C58 mice after one night as well as seven nights of twice-nightly injections. These effects did not reflect generalized motor behavior suppression as non-repetitive motor behaviors such as grooming, digging and eating were not reduced relative to vehicle. Sub-chronic drug treatment targeting striatopallidal neurons resulted in significant changes in the STN, including a four-fold increase in brain-derived neurotrophic factor (BDNF) mRNA expression as well as a significant increase in dendritic spine density. The present findings are consistent with, and extend, our prior work linking decreased functioning of the indirect basal ganglia pathway to expression of repetitive motor behavior in C58 mice and suggest novel therapeutic targets.
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PMID:Pharmacological targeting of striatal indirect pathway neurons improves subthalamic nucleus dysfunction and reduces repetitive behaviors in C58 mice. 3246 Nov 29