Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is generally believed that chronic alcohol consumption results in cerebellar atrophy and Purkinje cell loss, especially in the anterior vermal region. A post-mortem stereological design was applied to cerebella from 10 chronic male alcoholics (mean age 45.5 years) with a minimum of 10 years of severe addiction and 10 male controls (mean age 42.5 years). All alcoholics had pathoanatomical evidence of alcohol abuse but no clinical signs of Wernicke's encephalopathy. Cerebellum was divided into five different areas: the anterior and posterior lobe, the anterior and posterior vermis, and the flocculonodular lobe. The total cortex and white matter volume, the cerebellar surface area, the total Purkinje and granule cell number and density, and the mean volume of Purkinje cells and their cell nuclei were measured in all five regions using stereological methods. The volume of the granular layer was increased by 13% with an increase in layer thickness by 17% possibly due to oedema. Globally, the mean volume of the Purkinje cell perikaryon was decreased by 24% with a decrease in the volume of Purkinje cell nuclei by 16%. The increase of the granular layer and the decrease of Purkinje cell size resulted in a 21% global reduction of Purkinje cell density without a concomitant loss of neurons. No significant regional or global cortical and white matter atrophy was found in cerebella from alcoholics compared to controls.
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PMID:Reduction of Purkinje cell volume in cerebellum of alcoholics. 1506 31

Orexins are newfound hypothalamic neuropeptides implicated in the regulation of feeding behavior, sleep-wakefulness cycle, nociception, addiction, emotions, as well as narcolepsy. However, little is known about roles of orexins in motor control. Therefore, the present study was designed to investigate the effect of orexins on neuronal activity in the cerebellum, an important subcortical center for motor control. In this study, perfusing slices with orexin A (100 nM-1 microM) or orexin B (100 nM-1 microM) both produced neurons in the rat cerebellar interpositus nucleus (IN) a concentration-dependent excitatory response (96/143, 67.1%). Furthermore, both of the excitations induced by orexin A and B were not blocked by the low-Ca(2+)/high-Mg(2+) medium (n = 8), supporting a direct postsynaptic action of the peptides. Highly selective orexin 1 receptor antagonist SB-334867 did not block the excitatory response of cerebellar IN neurons to orexins (n = 22), but [Ala(11), D-Leu(15)] orexin B, a highly selective orexin 2 receptor (OX(2)R) agonist, mimicked the excitatory effect of orexins on the cerebellar neurons (n = 18). These results demonstrate that orexins excite the cerebellar IN neurons through OX(2)R and suggest that the central orexinergic nervous system may actively participate in motor control through its modulation on one of the final outputs of the spinocerebellum.
Cerebellum 2010 Mar
PMID:Orexins excite neurons of the rat cerebellar nucleus interpositus via orexin 2 receptors in vitro. 1992 32

Cerebellum controls motor coordination, balance, eye movement, and has been implicated in memory and addiction. As in other parts of the CNS, correct embryonic and postnatal development of the cerebellum is crucial for adequate performance in the adult. Cellular and molecular defects during cerebellar development can lead to severe phenotypes, such as ataxias and tumors. Knowing how the correct development occurs can shed light into the mechanisms of disease. Heparan sulfate proteoglycans are complex molecules present in every higher eukaryotic cells and changes in their level of expression as well as in their structure lead to drastic functional alterations. This work aimed to investigate changes in heparan sulfate proteoglycans expression during cerebellar development that could unveil control mechanisms. Using real time RT-PCR we evaluated the expression of syndecans, glypicans and modifying enzymes by isolated cerebellar granule cell precursors, and studied the influence of soluble glial factors on the expression of those genes. We evaluated the possible involvement of Runx transcription factors in the response of granule cell precursors to glial factors. Our data show for the first time that cerebellar granule cell precursors express members of the Runx family and that the expression of those genes can also be controlled by glial factors. Our results also show that the expression of all genes studied vary during postnatal development and treatment of precursors with glial factors indicate that the expression of heparan sulfate proteoglycan genes as well as genes encoding heparan sulfate modifying enzymes can be modulated by the microenvironment, reflecting the intricate relations between neuron and glia.
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PMID:Glial cells modulate heparan sulfate proteoglycan (HSPG) expression by neuronal precursors during early postnatal cerebellar development. 2063 66

Motor inhibition is an essential skill for fully adapted behavior requiring motor control and higher-order functions of motor cognition. A wide set of cortical and subcortical areas, including the right inferior frontal gyrus, the pre-supplementary motor area, and the subthalamic nucleus in the basal ganglia, contribute to convey the inhibitory command to the motor cortex. In the present review, we discuss how recent evidence supports the idea that the cerebellum may also have a relevant contribution in certain aspects of motor inhibition. This evidence were provided by behavioral data collected in patients with cerebellar lesions, functional magnetic resonance (fMRI) investigations conducted in clinical samples and in healthy participants, and by transcranial magnetic stimulation (TMS) techniques used to non-invasively test cerebello-motor functional connectivity. The application of these methods, combined with the execution of inhibitory tasks, could provide new evidence for a causal role of the effective cerebello-cortical connectivity in motor inhibition. Understanding the neurophysiological mechanisms that mediate motor inhibition through the cerebellum could be essential to design new rehabilitative protocols for treating several neurological and psychiatric disorders characterized by disinhibited behavior such as addiction, schizophrenia, attention deficit hyperactivity disorder (ADHD) and Parkinson's disease.
Cerebellum 2015 Feb
PMID:Is motor inhibition mediated by cerebello-cortical interactions? 2528 81

Cannabis is the third most used psychoactive drug worldwide. Despite being legally scheduled as a drug with high harm potential and no therapeutic utility in countries like the USA, evidence shows otherwise and legislative changes and reinterpretations of existing ambiguous laws make this drug increasingly available by legal means. Nevertheless, this substance is able to generate clear addiction syndromes in some individuals who use it, which are accompanied by brain alterations resembling those caused by other addictive drugs. Moreover, there is no available pharmacological treatment for this disorder. This fact motivates a deep study and comprehension of the neural basis of addiction-relevant cannabinoid effects. Interestingly, the cerebellum, a hindbrain structure which involvement in functions not related to motor control and planning is being increasingly recognized in the last decades, seems to be involved in the effects of addictive drugs and addiction-related processes and also presents a high density of cannabinoid receptors. Preclinical research on the involvement of the cerebellum in cannabis' effects has focused in the drug's motor incoordinating actions, potentially underestimating its participation in addiction. Therefore, this review addresses the studies reporting cerebellar involvement in cannabis effects both in experimental animals and human subjects and the possible relevance of these changes for addiction. Additionally, future experimental approaches will be proposed and hopefully this work will stimulate research on the cerebellum in cannabis addiction and help recognizing it as an important part of the neural circuitry affected in cannabis-related disorders.
Cerebellum 2019 Jun
PMID:The Cerebellum, THC, and Cannabis Addiction: Findings from Animal and Human Studies. 3061 May 40