Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebellum may be a common site of developmental abnormalities due to its protracted course of maturation. Recent studies have implicated morphological deviations of the cerebellum as responsible for specific behavioral and cognitive manifestations of autism. We investigated neuropsychology and quantitative MRI of the cerebellum in both high functioning subjects with autism and survivors of childhood leukemia treated with radiation and intrathecal chemotherapy. The results of neuropsychological testing revealed different patterns of cognitive deficits for the two groups, while the abnormal cerebellar morphology was similar for both groups. Since it is suggested that the cerebellum contributes to motor-attentional subsystems, the present data provide support for a cerebellar role in the governance of higher cognitive functions, found to be abnormal in both groups. However, the abnormal macromorphology of the cerebellar vermis described here appears to be non-specific to autism.
 ...
PMID:Cerebellar abnormality in autism: a nonspecific effect of early brain damage? 805 11

Cerebellar pathology has been associated with a number of developmental behavioral disorders, including autism spectrum disorders. Despite the fact that perinatal virus infections have been implicated in neurodevelopmental damage, few animal models have been developed to study the pathogenesis involved. One of the most interesting in vivo models of virus-induced cerebellar damage is the neonatal Borna disease virus (BDV) infection of the rat brain. The present review describes molecular, cellular, neuroanatomical, neurochemical and behavioral features of the BDV model and also provides a basis for a new understanding of the pathogenic mechanisms of cerebellar malformation and associated behavioral deficits.
Cerebellum 2003
PMID:Exploring the cerebellum with a new tool: neonatal Borna disease virus (BDV) infection of the rat's brain. 1288 36

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

Autism is a debilitating neurodevelopmental disorder of early childhood with both genetic and environmental origins. Immune system dysregulation has been hypothesized to be involved in this disorder. We quantified levels of glial fibrillary acidic protein (GFAP) and ss-actin in three areas of the brain, namely, area 9, area 40 and cerebellum, in age matched autistic and control postmortem specimen using SDS-PAGE and western blotting techniques. Significant elevations in levels of GFAP were observed in all three brain areas in autism. This report confirms a recent report showing microglial and astroglial activation in autism. Increased GFAP levels in autistic brains signify gliosis, reactive injury, and perturbed neuronal migration processes.
Cerebellum 2005
PMID:Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects. 1614 53

The article considers behavioral disturbances in children with anomalies of the cerebellum found by MRI studies. Presented are literature data on the relations between pathology of the cerebellum and early autism in children. The cerebellum is involved not only in movement coordination but also in social adaptation and speech communication. Cerebellum-specific genes expressed in early age are similar to those of hippocampus. Our own study of children with agenesis of the vermis cerebelli detected by MRI and behavioral disturbances included 20 children aged 3-15 years (mean age 7,05 years, 12 male, 8 female). Some autistic features have been found.
 ...
PMID:[Clinical and psychological features of children with agenesis of the vermis cerebelli]. 1697 92

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

A central aspect of the cerebellar cognitive affective syndrome is the dysregulation of affect that occurs when lesions involve the 'limbic cerebellum' (vermis and fastigial nucleus). In this case series we describe neuropsychiatric disturbances in adults and children with congenital lesions including cerebellar agenesis, dysplasia, and hypoplasia, and acquired conditions including cerebellar stroke, tumor, cerebellitis, trauma, and neurodegenerative disorders. The behaviors that we witnessed and that were described by patients and families included distractibility and hyperactivity, impulsiveness, disinhibition, anxiety, ritualistic and stereotypical behaviors, illogical thought and lack of empathy, as well as aggression and irritability. Ruminative and obsessive behaviors, dysphoria and depression, tactile defensiveness and sensory overload, apathy, childlike behavior, and inability to appreciate social boundaries and assign ulterior motives were also evident. We grouped these disparate neurobehavioral profiles into five major domains, characterized broadly as disorders of attentional control, emotional control, and social skill set as well as autism spectrum disorders, and psychosis spectrum disorders. Drawing on our dysmetria of thought hypothesis, we conceptualized the symptom complexes within each putative domain as reflecting either exaggeration (overshoot, hypermetria) or diminution (hypotonia, or hypometria) of responses to the internal or external environment. Some patients fluctuated between these two states. We consider the implications of these neurobehavioral observations for the care of patients with ataxia, discuss the broader role of the cerebellum in the pathogenesis of these neuropsychiatric symptoms, and revisit the possibility of using cerebellar stimulation to treat psychiatric disorders by enhancing cerebellar modulation of cognition and emotion.
Cerebellum 2007
PMID:The neuropsychiatry of the cerebellum - insights from the clinic. 1778 22

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


1 2 3 4 5 Next >>