Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence derived from both pharmacological and postmortem studies suggests that a disturbance of brain iron metabolism is involved in the pathophysiology of schizophrenia; i.e., the distribution of iron parallels that of dopamine, and variations in its brain concentration selectively modulate the binding affinity of the dopaminergic (D2) receptor. In the present study the authors examined the staining intensity of brain iron in postmortem specimens of 9 schizophrenic (SC) patients and 17 age-matched controls. Coronal sections were stained with the Perls's technique, photographed, and then studied using a computerized image analysis system. Optical density measurements were taken from the caudate nucleus, putamen, globus pallidus, and substantia nigra. This study revealed significant differences between groups only for the staining intensity of iron in the caudate nucleus (P less than 0.005). A review of the literature suggests that this finding may be the result of neuroleptic therapy and not a primary pathological feature of schizophrenia.
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PMID:Staining intensity of brain iron in patients with schizophrenia: a postmortem study. 162 59

Despite multiple lines of investigation the effect of neuroleptics on glutamate-mediated neurotransmission remains controversial. To study the effects of typical and atypical neuroleptics on selected parameters of glutamate-mediated neurotransmission, male Sprague-Dawley rats were randomly assigned to a 21-day oral treatment course with vehicle, haloperidol (HDL), or clozapine (CLZ). Coronal slices of rat brain were then incubated with tritiated ligands to measure NMDA, AMPA, and kainate receptor, and glutamate reuptake site density. Regions of interest included the frontal cortex, anterior cingulate cortex, dorsal striatum, ventral striatum, and the nucleus accumbens. CLZ increased the density of AMPA receptors significantly in the frontal and anterior cingulate cortices compared with normal controls. In the dorsal and ventral striatum, and nucleus accumbens as a whole, CLZ-treated rats had a higher AMPA receptor density compared with both the HDL- and vehicle-treated controls. Additionally, within the nucleus accumbens, CLZ-treated rats had a higher density of AMPA receptors compared with the HDL group in the core, and at trend level in the shell. There was a group by region interaction for NMDA receptor density, primarily reflecting the tendency of HDL treated rats to have high receptor densities in the frontal and anterior cingulate cortices. Kainate receptors and glutamate reuptake site densities did not differ significantly across groups. These results suggest a critical role for glutamate in the mediation of atypical antipsychotic drug action in anatomically-specific regions, and further encourage the investigation of glutamate neurotransmitter systems in schizophrenia.
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PMID:Differential effects of haloperidol and clozapine on ionotropic glutamate receptors in rats. 1052 21

Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg(-1) subcutaneously, or vehicle (control) at 24-36 h of life. At 5-7 weeks behavioural observations were made, and brains removed, fixed and sectioned. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia.
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PMID:Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia. 1604 96

The human hippocampus plays a central role in various neuropsychiatric disorders, such as temporal lobe epilepsy (TLE), Alzheimer's dementia, mild cognitive impairment, and schizophrenia. Its volume, morphology, inner structure, and function are of scientific and clinical interest. Magnetic resonance (MR) imaging is a widely employed tool in neuroradiological workup regarding changes in brain anatomy, (sub-) volumes, and cerebral function including the hippocampus. Gain in intrinsic MR signal provided by higher field strength scanners and concomitant improvements in spatial resolution seem highly valuable. An examination protocol permitting complete, high-resolution imaging of the human hippocampus at 7 T was implemented. Coronal proton density, T2, T2*, and fluid-attenuated inversion recovery contrasts were acquired as well as an isotropic 3D magnetization-prepared rapid acquisition gradient-echo (500 microm isotropic voxel dimension, noninterpolated). Observance of energy deposition restrictions within acceptable scan times remained challenging in the acquisition of thin, spin-echo-based sections. At the higher resolution enabled by 7 T, demarcation of the hippocampus and some internal features including gray/white matter differentiation and depiction of the hippocampal mantle becomes much more viable when compared with 1.5 T; thus, in the future, this imaging technology might help in the diagnosis of subtle hippocampal changes.
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PMID:The human hippocampus at 7 T--in vivo MRI. 1872 48

Our aim was to investigate if neonatal bilateral administration of lidocaine into the ventral hippocampus would cause behavioral changes related to schizophrenia. A neonatal ventral-hippocampal lesion (nVH lesion) was made with lidocaine in Wistar male pups. Two groups were formed, the first received lidocaine (4 mug/0.3 muL) and the second an equal volume of vehicle. At day 35 and 56, both groups were tested for social contact, immobility caused by clamping the neck and dorsal immobility, locomotor activity in an open field, and tail flick (TF) latency after a painful heat stimulus. All animals were then killed. Coronal cuts (7 mum) of the brain were obtained and each brain section was stained with cresyl violet-eosin. The animals which received the nVH lesion with lidocaine had decreased social interaction at both ages. The rats with lesions, only at day 58 postnatal, increased their distance traveled and ambulatory time, with a decrease in their nonambulatory and reset time. The rats with lesions had a longer duration of immobility caused by clamping the neck and a longer dorsal immobility at both days 34 and 57 compared to control rats. The lidocaine-treated group spent less time to deflect the tail compared to the control group at postpubertal age. The neonatal bilateral administration of lidocaine into the ventral hippocampus caused some alterations, such as chromatin condensation, nucleolus loss, and cell shrinkage, but glial proliferation was not seen. Neonatal bilateral lidocaine administration into the ventral hippocampus caused postpubertal behavioral changes.
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PMID:Neonatal bilateral lidocaine administration into the ventral hippocampus caused postpubertal behavioral changes: An animal model of neurodevelopmental psychopathological disorders. 1955 95

The 3-hydroxytyramine/dopamine is a monoamine of the catecholamine group and it is a precursor of the noradrenaline and adrenaline synthesis, in which the enzyme tyrosine hydroxylase acts as a rate-limiting enzyme. The dopaminergic nuclei retrorubral field (A8 group), substantia nigra pars compacta (A9 group) and ventral tegmental area (A10 group) are involved in three complex circuitries named mesostriatal, mesocortical and mesolimbic, which are directly related to various behavioral manifestations such as motor control, reward signaling in behavioral learning, motivation and pathological manifestations of Parkinson's disease and schizophrenia. The aim of this study was to describe the delimitation of A8, A9 and A10 groups and the morphology of their neurons in the brain of the rock cavy (Kerodon rupestris), a typical Brazilian Northeast rodent belonging to the suborder Hystricomorpha, family Caviidae. Coronal and sagittal sections of the rock cavy brains were submitted to Nissl staining and TH immunohistochemistry. The organization of these dopaminergic nuclei in the rock cavy brain is very similar to that found in other animals of the Rodentia order, except for the presence of the tail of the substantia nigra, which is found only in the species under study. The results revealed that, apart some morphological variations, A8, A9 and A10 groups are phylogenetically stable brain structures.
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PMID:A cytoarchitectonic and TH-immunohistochemistry characterization of the dopamine cell groups in the substantia nigra, ventral tegmental area and retrorubral field in the rock cavy (Kerodon rupestris). 2444 14

It is widely known that the catecholamine group is formed by dopamine, noradrenaline and adrenaline. Its synthesis is regulated by the enzyme called tyrosine hydroxylase. 3-hydroxytyramine/dopamine (DA) is a precursor of noradrenaline and adrenaline synthesis and acts as a neurotransmitter in the central nervous system. The three main nuclei, being the retrorubral field (A8 group), the substantia nigra pars compacta (A9 group) and the ventral tegmental area (A10 group), are arranged in the die-mesencephalic portion and are involved in three complex circuitries - the mesostriatal, mesolimbic and mesocortical pathways. These pathways are involved in behavioral manifestations, motricity, learning, reward and also in pathological conditions such as Parkinson's disease and schizophrenia. The aim of this study was to perform a morphological analysis of the A8, A9 and A10 groups in the common marmoset (Callithrix jacchus - a neotropical primate), whose morphological and functional characteristics support its suitability for use in biomedical research. Coronal sections of the marmoset brain were submitted to Nissl staining and TH-immunohistochemistry. The morphology of the neurons made it possible to subdivide the A10 group into seven distinct regions: interfascicular nucleus, raphe rostral linear nucleus and raphe caudal linear nucleus in the middle line; paranigral and parainterfascicular nucleus in the middle zone; the rostral portion of the ventral tegmental area nucleus and parabrachial pigmented nucleus located in the dorsolateral portion of the mesencephalic tegmentum. The A9 group was divided into four regions: substantia nigra compacta dorsal and ventral tiers; substantia nigra compacta lateral and medial clusters. No subdivisions were made for the A8 group. These results reveal that A8, A9 and A10 are phylogenetically stable across species. As such, further studies concerning such divisions are necessary in order to evaluate the occurrence of subdivisions that express DA in other primate species, with the aim of characterizing its functional relevance.
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PMID:Nuclear organization of the substantia nigra, ventral tegmental area and retrorubral field of the common marmoset (Callithrix jacchus): A cytoarchitectonic and TH-immunohistochemistry study. 2729 10