The decrease of dopamine D₂/D₃ receptor densities in the putamen and nucleus caudatus goes parallel with maintained levels of CB₁ cannabinoid receptors in Parkinson's disease: a preliminary autoradiographic study with the selective dopamine D₂/D₃ antagonist [³H]raclopride and the novel CB₁ inverse agonist [¹²⁵I]SD7015

Cannabinoid type-1 receptors (CB?Rs) modulate synaptic neurotransmission by participating in retrograde signaling in the adult brain. Increasing evidence suggests that cannabinoids through CB?Rs play an important role in the regulation of motor activities in the striatum. In the present study, we used human brain samples to examine the relationship between CB?R and dopamine receptor density in case of Parkinson's disease (PD). Post mortem putamen, nucleus caudatus and medial frontal gyrus samples obtained from PD patients were used for CB?R and dopamine D?/D? receptor autoradiography. [12?I]SD7015, a novel selective CB?R inverse agonist, developed by a number of the present co-authors, and [3H]raclopride, a dopamine D?/D? antagonist, were used as radioligands. Our results demonstrate unchanged CB?R density in the putamen and nucleus caudatus of deceased PD patients, treated with levodopa (L-DOPA). At the same time dopamine D?/D? receptors displayed significantly decreased density levels in case of PD putamen (control: 47.97 ± 10.00 fmol/g, PD: 3.73 ± 0.07 fmol/g (mean ± SEM), p<0.05) and nucleus caudatus (control: 30.26 ± 2.48 fmol/g, PD: 12.84 ± 5.49 fmol/g, p<0.0005) samples. In contrast to the putamen and the nucleus caudatus, in the medial frontal gyrus neither receptor densities were affected. Our data suggest the presence of an unaltered CB?R population even in late stages of levodopa treated PD. This further supports the presence of an intact CB?R population which, in line with the conclusion of earlier publications, may be utilized as a pharmacological target in the treatment of PD. Furthermore we found discrepancy between a maintained CB?R population and a decreased dopamine D?/D? receptor population in PD striatum. The precise explanation of this conundrum requires further studies with simultaneous examination of the central cannabinoid and dopaminergic systems in PD using higher sample size.     

The default mode network integrity in patients with Parkinson’s disease is levodopa equivalent dose-dependent

Disturbances in the default mode network (DMN) have been described in many neurological and psychiatric disorders including Parkinson’s disease (PD). The DMN is characterized by basal activity that increases during rest or passive visual fixation and decreases (“deactivates”) during cognitive tasks. The network is believed to be involved in cognitive processes. We examined the DMN in PD patients on dopaminergic medication with normal cognitive performance compared to age- and gender-matched healthy controls (HC) using fMRI and three methodological procedures: independent component analysis of resting-state data, analysis of deactivation during a complex visual scene-encoding task, and seed-based functional connectivity analysis. In the PD group, we also studied the effect of dopaminergic medication on the DMN integrity. We did not find any difference between the PD and HC groups in the DMN, but using the daily levodopa equivalent dose as a covariate, we observed an enhanced functional connectivity of the DMN in the posterior cingulate cortex and decreased activation in the left parahippocampal gyrus during the cognitive task. We conclude that dopaminergic therapy has a specific effect on both the DMN integrity and task-related brain activations in cognitively unimpaired PD patients, and these effects seem to be dose-dependent.     

Prefrontal but not temporal grey matter changes in males with first-episode schizophrenia

INTRODUCTION: Changes of brain morphology are now considered as a part of the pathology of schizophrenia. Voxel-based morphometry may be used to study regional changes of the grey matter in the whole brain. It is advantageous to study first-episode patients to prevent the influence of many possible biasing factors when trying to identify primary pathological processes underlying the manifestation of the illness. OBJECTIVE: To investigate regional grey matter changes in the first-episode schizophrenia patients. METHODS: Optimized voxel-based morphometry was used to detect changes in grey matter volume in 22 patients with first-episode schizophrenia compared with 18 healthy volunteers of comparable age, gender and handedness. RESULTS: The first-episode schizophrenia group had significantly reduced grey matter volume in the prefrontal cortex (inferior and middle prefrontal gyrus, cingulate gyrus). We identified no differences in the temporal cortex. CONCLUSION: Our data support the theoretical assumption that prefrontal dysfunction underlines the primary pathology and clinical manifestation of schizophrenia. We are inclined to explain the differences in the pattern of morphological changes reported in other first-episode studies--especially the lack of changes in the temporal cortex--by heterogeneity of schizophrenia, potential progression and antipsychotic medication effect.     

The medial paralemniscal nucleus and its afferent neuronal connections in rat

Previously, we described a cell group expressing tuberoinfundibular peptide of 39 residues (TIP39) in the lateral pontomesencephalic tegmentum, and referred to it as the medial paralemniscal nucleus (MPL). To identify this nucleus further in rat, we have now characterized the MPL cytoarchitectonically on coronal, sagittal, and horizontal serial sections. Neurons in the MPL have a columnar arrangement distinct from adjacent areas. The MPL is bordered by the intermediate nucleus of the lateral lemniscus nucleus laterally, the oral pontine reticular formation medially, and the rubrospinal tract ventrally, whereas the A7 noradrenergic cell group is located immediately mediocaudal to the MPL. TIP39-immunoreactive neurons are distributed throughout the cytoarchitectonically defined MPL and constitute 75% of its neurons as assessed by double labeling of TIP39 with a fluorescent Nissl dye or NeuN. Furthermore, we investigated the neuronal inputs to the MPL by using the retrograde tracer cholera toxin B subunit. The MPL has afferent neuronal connections distinct from adjacent brain regions including major inputs from the auditory cortex, medial part of the medial geniculate body, superior colliculus, external and dorsal cortices of the inferior colliculus, periolivary area, lateral preoptic area, hypothalamic ventromedial nucleus, lateral and dorsal hypothalamic areas, subparafascicular and posterior intralaminar thalamic nuclei, periaqueductal gray, and cuneiform nucleus. In addition, injection of the anterograde tracer biotinylated dextran amine into the auditory cortex and the hypothalamic ventromedial nucleus confirmed projections from these areas to the distinct MPL. The afferent neuronal connections of the MPL suggest its involvement in auditory and reproductive functions.     

Clinical symptoms related to renal cell carcinoma are independent prognostic factors for intraoperative complications and overall survival

Objective  

It is not yet elucidated whether the symptoms related to renal cell carcinoma have a strong effect on intraoperative complications or survival. We aimed to investigate this association in a cohort of renal cancer patients operated on between June 1997 and December 2004 at the Department of Urology, Semmelweis University School of Medicine.     

Evaluation of 100 laparoscopic varicocele operations with preservation of testicular artery and ligation of collateral vein in children and adolescents

OBJECTIVES: To introduce a useful technique for identifying any collateral veins during laparoscopic varicocele operation and to evaluate our long-term results with this technique after 100 cases. METHODS: A new method was used to detect an incidental collateral vein. During surgery the patient was placed in anti-Trendelenburg position after introducing laparoscopic instruments until the dilated scrotal varicose filled up with blood. The main spermatic vein was then grasped atraumatically and the blood was pressed out manually from the scrotum. During this manoeuvre any existing collateral vein/veins became dilated and could be easily identified. The dilated spermatic vein and also any collateral vessel were first prepared then clipped. RESULTS: Out of the 100 patients, collateral veins were detected and ligated in 19 cases. In 15 cases a single collateral, in 4 cases two collaterals, and in the remaining 81 children no collateral veins were found. The testicular artery was identified in all operations as a pulsatile vessel. At a mean of 24 months (range 6-60 months) follow-up recurrence occurred in one patient and in five children hydrocele developed postoperatively. Testicular atrophy and severe intra- or postoperative complication did not occur in any patient of this series. CONCLUSION: The identification of incidental collateral vein by this method and preservation of the testicular artery resulted in a very good success rate in children and adolescents treated by laparoscopic varicocele operation.     

Acute audiogenic stress-induced activation of CRH neurons in the hypothalamic paraventricular nucleus and catecholaminergic neurons in the medulla oblongata

Strong c-fos expression was induced in neuronal cells of several brain nuclei and the auditory cortex by a short duration auditory stimulation (white noise) in rats. By double immunostaining, Fos-immunoreactive cell nuclei appeared in corticotropin-releasing hormone (CRH)-containing neurons in the hypothalamic paraventricular nucleus, but not in CRH neurons elsewhere in the brain including the central nucleus of the amygdala. Among brain catecholaminergic neurons, only cells in the medulla oblongata (in the A1/C1and A2/C2 cell groups) established double immunostaining for Fos and tyrosine hydroxylase. Sound stimulus in rats with unilateral tympanotomy and plugging the airways resulted in side differences of Fos immunoreactivity in neurons of the auditory pathways and the auditory cortex, but the effect was bilateral in hypothalamic and amygdaloid nuclei. The present data provide evidence for the participation of CRH-synthesizing neurons in hypothalamus and medullary catecholaminergic neurons in the central organization of responses to audiogenic stress stimuli.     

Synaptic targets of commissural interneurons in the lumbar spinal cord of neonatal rats

There is strong evidence that commissural interneurons, neurons with axons that extend to the contralateral side of the spinal cord, play an important role in the coordination of left/right alternation during locomotion. In this study we investigated the projections of commissural interneurons to motor neurons and other commissural interneurons on the other side of the spinal cord in neonatal rats. To establish whether there are direct contacts between axons of commissural interneurons and motor neurons, we carried out two series of experiments. In the first experiment we injected biotinylated dextran amine (BDA) into the lateral motor column to retrogradely label commissural interneurons that may have direct projections to motor neurons. Stained neurons were recovered in the ventromedial areas of the contralateral gray matter in substantial numbers. In the second experiment BDA was injected into the ventromedial gray matter on one side of the lumbar spinal cord, whereas motor neurons were simultaneously labeled on the opposite side by applying biocytin onto the ventral roots. BDA injections into the ventromedial gray matter labeled a strong axon bundle that arose from the site of injection, crossed the midline in the ventral commissure, and extensively arborized in the contralateral ventral gray matter. Many of these axons made close appositions with dendrites and somata of motor neurons and also with commissural interneurons retrogradely labeled with BDA. The results suggest that commissural interneurons may establish monosynaptic contacts with motor neurons on the opposite side of the spinal cord. Our findings also indicate that direct reciprocal connections between commissural interneurons on the two sides of the spinal cord may also exist.