Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebellum-like structures in fish appear to act as adaptive sensory processors, in which learned predictions about sensory input are generated and subtracted from actual sensory input, allowing unpredicted inputs to stand out. Pairing sensory input with centrally originating predictive signals, such as corollary discharge signals linked to motor commands, results in neural responses to the predictive signals alone that are 'negative images' of the previously paired sensory responses. Adding these 'negative images' to actual sensory inputs minimizes the neural response to predictable sensory features. At the cellular level, sensory input is relayed to the basal region of Purkinje-like cells, whereas predictive signals are relayed by parallel fibres to the apical dendrites of the same cells. The generation of negative images could be explained by plasticity at parallel fibre synapses. We show here that such plasticity exists in the electrosensory lobe of mormyrid electric fish and that it has the necessary properties for such a model: it is reversible, anti-hebbian (excitatory postsynaptic potentials (EPSPs) are depressed after pairing with a postsynaptic spike) and tightly dependent on the sequence of pre- and postsynaptic events, with depression occurring only if the postsynaptic spike follows EPSP onset within 60 ms.
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PMID:Synaptic plasticity in a cerebellum-like structure depends on temporal order. 915 91

Depression is one of the most common psychiatric illnesses. Its influence on brain perfusion has been demonstrated, but conflicting data exist on follow-up after drug treatment. The aim of our study was to evaluate the effects of antidepressant drugs on regional cerebral blood flow (rCBF) in patients with depression after 3 weeks and 6 months of drug therapy. Clinical criteria for depression without psychosis were met according to psychiatric evaluation. Severity of depression was evaluated with the Hamilton Depression Rating Scale (HAMD) before every scintigraphic study. rCBF was assessed using technetium-99m bicisate (Neurolite) brain single-photon emission tomography in nine patients with severe depression before the beginning of antidepressant drug therapy and 3 weeks and six months after initiation of therapy. Only patients with no change in antidepressant medication during the study were included. No antipsychotic drugs were used. Cerebellum was used as the reference region. rCBF was evaluated for eight regions in each study in three consecutive transversal slices. Follow-up studies were compared with the baseline study. The mean HAMD score was 25.5 points initially, 16 at the second examination and 8.8 after 6 months. Global CBF was decreased compared with the reference region in drug-free patients. Perfusion of left frontal and temporal regions was significantly lower (P < 0.005) in comparison with the contralateral side. After therapy, a moderate decrease in perfusion was seen in the right frontal region (P < 0.05). Perfusion decreased further after 6 months in the right frontal (P < 0.005) and temporal regions (P < 0.01). The highly significant asymmetry in perfusion between the left and right frontal and temporal lobes almost disappeared during treatment. Our findings implicate dysfunction of the frontal and temporal cortex in clinically depressed patients before specific drug treatment. Clinical improvement and decreases in HAMD score after 3 weeks and after 6 months reflect the treatment effect on mood-related rCBF changes.
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PMID:Evaluation of brain perfusion with technetium-99m bicisate single-photon emission tomography in patients with depressive disorder before and after drug treatment. 981 81

Metabotropic glutamate receptors (mGluRs) are a family of proteins that have seven transmembrane segments and that couple to G proteins. They differ from ionotropic glutamate receptors in that they do not form ion channels but instead affect intracellular chemical messenger systems. Eight genes coding for different subtypes of mGluRs have been identified to date and numbered accordingly in the order in which the cDNAs were cloned. Based on their principal signal-transduction capabilities in recombinant expression systems and sequence similarities, the family of mGluR subtypes is subdivided into three groups. Group 1 mGluRs (consisting of mGluR1 and 5) functionally couple to phospholipase C and affect the IP3/Ca2+ signaling pathway. The subtypes of group 2 (mGluR2 and 3) and group 3 (mGluR4, 6 7 and 8) inhibit adenylate cyclase and, thereby, mediate a decrease in cAMP concentration. All mGluR subtypes are found in the cerebellar cortex with the exception of mGluR6 which is exclusively expressed in the retina. At the parallel fiber-Purkinje cell synapses mGluR1 is localized in the peri- and extra-synaptic membrane of Purkinje cells. The main focus of this review deals with the functions of this postsynaptically localized mGluR1. These functions include (i) mediation of an inward current and a slow excitatory postsynaptic potential, and (ii) a role in induction of parallel fiber-Purkinje cell long-term depression. We discuss the mechanism underlying the mGluR1-mediated postsynaptic current as well as current theories on the role of mGluR1 in parallel fiber-Purkinje cell long-term depression.
Cerebellum
PMID:Metabotropic glutamate receptors in the cerebellum with a focus on their function in Purkinje cells. 1287 70

Cerebellar long-term depression (LTD) is classically observed when climbing fibers, originating from the inferior olive, and parallel fibers, axons of granule cells, are activated repetitively and synchronously. On the basis that the climbing fiber signals errors in motor performance, LTD provides a mechanism of learning whereby inappropriate motor signals, relayed to the cerebellar cortex by parallel fibers, are selectively weakened through their repeated, close temporal association with climbing fiber activity. LTD therefore provides a cellular substrate for error-driven motor learning in the cerebellar cortex. In recent years, it has become apparent that depression at this synapse can also occur without the need for concurrent climbing fiber activation provided the parallel fibers are activated in such a way as to mobilize calcium within the Purkinje cell. A form of long-term potentiation (LTP) has also been uncovered at this synapse, which similarly relies only upon parallel fiber activation. In brain slice preparations and contrary to expectation, each of these forms of parallel fiber induced plasticity, as well as classical LTD, does not remain confined to activated parallel fibers as previously thought, but both depression and potentiation have the capacity to spread to neighboring parallel fiber synapses several tens of microns away from the activated fibers. Here, the cellular mechanisms responsible for the induction and heterosynaptic spread of parallel fiber LTP and LTD are compared to those involved in classical LTD and the physiological implications that the heterosynaptic spread of plasticity may have on cerebellar signal processing are discussed.
Cerebellum
PMID:Parallel fiber plasticity. 1287 69

The cerebellum is a central organ in the control of motor learning and performance. In this respect, the cellular plasticity model systems of multiple climbing fiber elimination and long-term depression have been intensively studied. The signalling pathways involved in these plastic changes are now well understood on a molecular level and protein kinase C (PKC) activity appears to be crucially involved in both processes. Furthermore, as shown in recent studies, Purkinje cell dendritic development also critically depends on the activity of PKC. Thereby, the Ca(2+)-dependent PKC subtypes, activated by synaptic inputs through metabotropic glutamate receptors, trigger functional changes as well as long-term anatomical maturation of the Purkinje cell dendritic tree during cerebellar development at different time levels. This review summarizes these findings and forwards the hypothesis of a link between the functional mechanisms underlying LTD and the differentiation of Purkinje cell dendrites.
Cerebellum 2003
PMID:Protein kinase C: its role in activity-dependent Purkinje cell dendritic development and plasticity. 1450 70

The pontine nuclei relay information derived from the cerebral cortex to the cerebellum. In addition to the motor command signals generated in the motor cortex, the cerebellum may generate motor command signals independent of the cerebral cortex using pontine nuclei-mediated signals. The cerebellar motor command signals generated in the vermis-medial cerebellar nuclear system may directly drive peripheral motoneurons in simple and autonomic movements. Those generated in the hemisphere-lateral cerebellar nuclear system, which are used in complicated movements, may not only drive the premotor or motor nuclei but may also be fed back to the cerebellum through the parvocellular red nucleus-inferior olive pathway, and may be compared with the motor command signals generated in the cerebral cortex. The long-term depression of parallel fiber-Purkinje cell synapses may be utilized in optimizing these cerebellar motor command signals. Voluntary movements may be executed through cooperation of the cerebellum- and cerebrum-generated motor command signals.
Cerebellum 2004
PMID:Pontine nuclei-mediated cerebello-cerebral interactions and its functional role. 1507 62

It is established that cerebellar nuclei exert a significant effect on the excitability of spinal neurons. However, their output is heterogeneous. Conditioning trains of dentate nucleus stimuli are known to modify the post-synaptic potentials evoked in motoneurons by stimulation of group Ia and Ib afferents in appropriate peripheral nerves. The role of the interpositus nucleus in the modulation of the excitability of rat spinal cord remains unclear. We investigated the interactions between tetrodotoxin (TTX)-induced inactivation of the interpositus cerebellar nuclei and repetitive electrical stimulation of the ipsilateral sciatic nerve (proximal segment) in the anesthetized rat. TTX (10 microM) was administered in cerebellar nuclei by the technique of microdialysis (coordinates of the extremity of the guide related to bregma: AP: -11.6, L: +2.3, V: -4.6). Peripheral stimulation consisted of trains of electric stimuli at a rate of 10 Hz, which were repeated every second during 1 hour. Stimulus intensity was adjusted to produce constant somatosensory evoked potentials. H-reflex, F-wave and M responses of the plantaris muscles were analysed ipsilaterally. H-reflex recruitment curve, Hmax/Mmax ratios, F-wave persistence and mean F/mean M ratios were studied. Functional blockade of cerebellar interpositus nucleus reduced the slope of H-reflex recruitment curve without affecting the Hmax/Mmax ratio, and depressed both F-waves persistence and mean F/mean M ratios. Concomitant repetitive stimulation of the sciatic nerve counteracted the depression of the H-reflex recruitment curve, without interacting with F-waves depression. Our results (1) show that TTX-sensitive sodium channels in cerebellar nucleus interpositus modulate the H-reflex recruitment, and (2) reveal an interaction between TTX-sensitive sodium channels in cerebellar nuclei and afferent repetitive activity not described so far.
Cerebellum 2004
PMID:Interaction between repetitive stimulation of the sciatic nerve and functional ablation of cerebellar nucleus interpositus in the rat. 1507 64

Neuronal calcium sensor-1 (NCS-1) is a member of EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. In this mini-review, we first summarize distribution of NCS-1 in the cerebellum. NCS-1 is mainly detected in postsynaptic sites, such as somata and dendrites of Purkinje cells, stellate/basket cells and granule cells. In addition, GABAergic inhibitory stellate/basket cell axon terminals also contain NCS-1. Secondly, we describe cerebellar compartmentation defined by NCS-1. The NCS-1 immunostaining displayed characteristic parasagittal-banding pattern in the Purkinje cell layer and molecular layer, whereas there were no apparent bands in the granule cell layer. The alternating positively and negatively NCS-1-labeled Purkinje cell clusters contributed to this cerebellar compartmentation. In contrast, stellate/basket cells were uniformly NCS-1-positive throughout the cerebellum. Interestingly, NCS-1 and zebrin II exhibited a similar parasagittal-banding pattern. But it is noteworthy that NCS-1-negative/zebrin II-positive Purkinje cell clusters were detected selectively in anterior lobule vermis and paraflocculus. These results suggest that NCS-1 defines a novel pattern of cerebellar cortical compartmentation. Lastly, we describe recent data suggesting some relationship between NCS-1 and cerebellar long-term depression-related molecules, and discuss the possible role of NCS-1 in the cerebellum.
Cerebellum 2004
PMID:Expression and possible role of neuronal calcium sensor-1 in the cerebellum. 1523 74

Effective, pharmacologic approaches to the treatment of cerebellar ataxia are lacking or inadequate. We recently reported preliminary evidence that tandospirone citrate (tandospirone), a 5-HT1A agonist, improved cerebellar ataxia in patients with Machado-Joseph disease (MJD). In the course of that study, we found that such treatment also alleviated the pain associated with cold sensations in the legs, insomnia, anorexia, and depression, all of which are thought to be mediated through activation of the 5-HT1A receptor. In this paper, we reviewed the few published clinical trials that involved the use of 5-HT1A receptor agonists for the treatment of cerebellar ataxia, and discussed the current theories regarding their mechanism of action. Cortical cerebellar atrophy (CCA) was reported, in a double-blind study, to be amenable to treatment with tandospirone. Other types of spinocerebellar degeneration (SCD) i.e., olivopontocerebellar atrophy (OPCA) and Machado-Joseph disease (MJD) have also been reported to respond to the drug, but these have been small studies. Responsive patients exhibited only mild ataxia. The doses of 5-HT1A agonists that have been used successfully ranged from 12.5 mg/day to 60 mg/day (or 1 mg/kg), and were well tolerated by most patients.
Cerebellum 2005
PMID:Treatment of cerebellar ataxia with 5-HT1A agonist. 1614 54

For decennia the cerebellum has largely been excluded from scientific enquiry beyond motor function. However, the intimate afferent and efferent connections to the midbrain and limbic system provide for the neuroanatomical foundation of cerebellar involvement in emotion and emotional disorders. Moreover, an increasing body of empirical evidence indicates that the cerebellum may be involved in emotion regulation. Both functional and structural abnormalities of the cerebellum have been demonstrated in emotional disorders, including depression and schizophrenia. Research shows that the functional repertoire of the cerebellum is broader than previously thought and its involvement in emotion is noteworthy.
Cerebellum 2005
PMID:The cerebellum on the rise in human emotion. 1632 85


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