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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent postmortem and functional imaging studies have revealed that cerebellar abnormalities may play a role in the pathophysiology of schizophrenia. Cerebellum is a part of the cortical-subcortical-cerebellar circuitry that is involved in higher cognitive functions. Deficits in cognition, including information, executive functions, attention, emotion, and memory have been described in patients with schizophrenia. Given the pivotal role of mitogen-activated protein (MAP) kinase pathways in regulation of neuronal function and especially the role of extracellular-signal regulated kinase (ERK) in synaptic plasticity, cell survival, learning and memory, the importance of MAP kinases in schizophrenia is being increasingly recognized. In this mini-review is summarized recent evidence from human postmortem studies and the phencyclidine (PCP) pharmacological model of schizophrenia that ERK signaling pathway could contribute to the pathogenic events that occur in the cerebellum in schizophrenia.
Cerebellum 2004
PMID:The role of the extracellular signal-regulated kinase pathway in cerebellar abnormalities in schizophrenia. 1523 76

Nitric oxide (NO) is a diffusible, multifunctional signaling molecule found in many areas of the brain. NO signaling is involved in a wide array of neurophysiological functions including synaptogenesis, modulation of neurotransmitter release, synaptic plasticity, central nervous system blood flow and cell death. NO synthase (NOS) activity regulates the production of NO and the cerebellum expresses high levels of nitric oxide synthase (NOS) in granule, stellate and basket cells. Cerebellar mutant mice provide excellent opportunities to study changes of NO/NOS concentrations and activities to gain a greater understanding of the roles of NO and NOS in cerebellar function. Here, we have reviewed the current understanding of the functional roles of NO and NOS in the cerebellum and present NO/NOS activities that have been described in various cerebellar mutant mice and NOS knockout mice. NO appears to exert neuroprotective effects at low to moderate concentrations, whereas NO becomes neurotoxic as the concentration increases. Excessive NO production can cause oxidative stress to neurons, ultimately impairing neuronal function and result in neuronal cell death. Based on their genetics and cerebellar histopathology, some of cerebellar mutant mice display similarities with human neurological conditions and may prove to be valuable models to study several human neurological disorders, such as autism and schizophrenia.
Cerebellum 2004
PMID:Neuronal nitric oxide synthase expression in cerebellar mutant mice. 1554 2

Recent evidence from neuroimaging studies suggests that neural dysfunction is involved in the pathophysiology of schizophrenia. Diffusion tensor imaging (DTI) is a technique that has the potential to detect subtle disruptions of neural connectivity. Fractional anisotropy (FA), which is measured by DTI, is a measure of the directionality of diffusion anisotropy. Decrease in FA indicates abnormalities of white matter due to increased water diffusion accompanied by an increase in extracellular space. In the literature, previous studies reported that patients with schizophrenia showed widespread lower FA in the white matter. These findings suggest that patients with schizophrenia have microstructural lesions in the cerebral white matter. We used DTI to determine whether neural connectivity was disturbed in the middle cerebellar peduncles in schizophrenic subjects. We found a significant FA reduction in the middle cerebellar peduncle in patients with schizophrenia. Therefore, neural disconnectivity between the cerebellum and cerebrum was considered present in patients with schizophrenia and may be involved in the pathology of schizophrenia. This review provides current findings regarding DTI study on the cerebellar peduncle in patients with schizophrenia.
Cerebellum 2005
PMID:Diffusion tensor imaging study of the middle cerebellar peduncles in patients with schizophrenia. 1603 94

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

Accumulating evidence from both human lesion and functional neuroimaging studies appears to support the hypothesis that the cerebellum contributes to non-motor functions. Along similar lines, cognitive, affective and behavioural changes in psychiatric disorders, such as autism, schizophrenia and dyslexia, have been linked to structural cerebellar abnormalities. The aim of this special issue was to evaluate the current knowledge base after more than 20 years of controversial discussion. The contributions of the special issue cover the most important cognitive domains, i.e., attention, memory and learning, executive control, language and visuospatial function. The available empirical evidence suggests that cognitive changes in patients with cerebellar dysfunction are mild and clearly less severe than the impairments observed after lesions to neocortical areas to which the cerebellum is closely connected via different cerebro-cerebellar loops. Frequently cited early findings, e.g., with respect to a specific cerebellar involvement in attention, have not been replicated or might be confounded by motor or working memory demands of the respective attention task. On the other hand, there is now convincing evidence for a cerebellar involvement in the mediation of a range of cognitive domains, most notably verbal working memory. Verbal working memory problems may partly underlie the compromised performance of cerebellar lesion patients on at least some complex cognitive tasks. Although investigations have moved from anecdotical case reports to hypothesis-driven controlled clinical group studies based on sound methods which are complemented by state-of-the-art functional neuroimaging studies, the empirical evidence available so far does not yet allow a convincing theory of the mechanisms of a cerebellar involvement in cognitive function. Future studies are clearly needed to further elucidate the nature of the processes linked to cerebellar mediation of cognitive processes and their possible link to motor theories of cerebellar function, e.g., its role in prediction and/or timing.
Cerebellum 2007
PMID:Cerebellar contributions to cognitive functions: a progress report after two decades of research. 1778 10

The cerebellum is densely interconnected with sensory-motor areas of the cerebral cortex, and in man, the great expansion of the association areas of cerebral cortex is also paralleled by an expansion of the lateral cerebellar hemispheres. It is therefore likely that these circuits contribute to non-motor cognitive functions, but this is still a controversial issue. One approach is to examine evidence from neuropsychiatric disorders of cerebellar involvement. In this review, we narrow this search to test whether there is evidence of motor dysfunction associated with neuropsychiatric disorders consistent with disruption of cerebellar motor function. While we do find such evidence, especially in autism, schizophrenia and dyslexia, we caution that the restricted set of motor symptoms does not suggest global cerebellar dysfunction. Moreover, these symptoms may also reflect involvement of other, extra-cerebellar circuits and detailed examination of specific sub groups of individuals within each disorder may help to relate such motor symptoms to cerebellar morphology.
Cerebellum 2007
PMID:The cerebellum and motor dysfunction in neuropsychiatric disorders. 1778 23

Neurosteroids play an important role in the development of the cerebellum. In particular, estradiol and progesterone appear capable of inducing increases in dendritic spine density during development, and there is evidence that both are synthesized de novo in the cerebellum during critical developmental periods. In normal neonates and adults, there are few differences in the cerebellum between the sexes and most studies indicate that hormone and receptor levels also do not differ significantly during development. However, the sexes do differ significantly in risk of neuropsychological diseases associated with cerebellar pathology, and in animal models there are noticeable sex differences in the response to insult and genetic mutation. In both humans and animals, males tend to fare worse. Boys are more at risk for autism and Attention Deficit Hyperactivity Disorder than girls, and schizophrenia manifests at an earlier age in men. In rats males fare worse than females after perinatal exposure to polychlorinated biphenyls, and male mice heterozygous for the staggerer and reeler mutation show a more severe phenotype. Although very recent evidence suggests that differences in neurosteroid levels between the sexes in diseased animals may play a role in generating different disease phenotypes, the reason this hormonal difference occurs in diseased but not normal animals is currently unknown.
Cerebellum 2008
PMID:Steroids, sex and the cerebellar cortex: implications for human disease. 1841 72

Schizophrenia and autism are neurodevelopmental diseases that have genetic as well as environmental etiologies. Both disorders have been associated with prenatal viral infection. Brain imaging and postmortem studies have found alterations in the structure of the cerebellum as well as changes in gene expression. Our laboratory has developed an animal model using prenatal infection of mice with human influenza virus that has demonstrated changes in behavior, pharmacology, structure, and gene expression in the brains of exposed offspring. In the current communication we describe altered expression of cerebellar genes associated with development of brain disorder in a mouse model for schizophrenia and autism and correlate these changes with those involved in the pathology of these two disorders.
Cerebellum 2008
PMID:The role of cerebellar genes in pathology of autism and schizophrenia. 1841 86

Magnetic resonance imaging studies frequently report abnormalities of the cerebellar vermis in schizophrenia, though with some discrepancies as to the nature and location of such abnormalities. Imaging studies typically investigate volumetric differences between groups. Yet substantial evidence supports the hypothesis that grey and white matter proportions in the mammalian brain are controlled by scaling relationships. If strong proportional relationships between grey and white matter tissue volumes are observed in the healthy vermis, then disturbances to these proportions might characterize vermian dysmorphology in schizophrenia. Measures of grey and white matter tissue volumes from three anatomical divisions of the vermis were obtained from 52 patients with chronic schizophrenia and 55 healthy controls. Cross-correlations of the tissue class volumes were computed for each subject group, controlling for age. The number of significant correlations in each group were compared. In addition, the grey/white matter ratio was computed within and across each vermian division. Differences in mean and variance were assessed using t and F tests. A false discovery rate of 0.05 controlled for multiple comparisons. Among controls, 11 of 15 correlations were significant. Among patients, eight of 15 correlations were significant. Five of the nine grey/white matter ratios had an increased mean in the patient group, and all of the variances were trend level or significantly increased in the patients. Tissue class volumes in the cerebellar vermis were strongly interrelated in controls. These relationships were disturbed in patients with schizophrenia.
Cerebellum 2009 Mar
PMID:Grey and white matter proportional relationships in the cerebellar vermis altered in schizophrenia. 1897 81

Brain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2-4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders.
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PMID:A structural MRI study of human brain development from birth to 2 years. 1902 11


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