Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytomegalovirus (CMV) is the most significant infectious cause of brain disorders in humans. Although the brain is the principal target organ for CMV infection in infants with congenital infection and in immunocompromised patients, little has been known about cellular events in pathogenesis of the brain disorders. Mouse models have been developed by the authors for studying the cell tropism, infectious dynamics of CMV infection and the effects of CMV infection on proliferation, regeneration and differentiation of neural cells. It has been shown, using brain slice cultures and neurospheres, that neural stem progenitor (NSP) cells are the most susceptible to CMV infection in developing brains. The NSP cells are also susceptible to CMV infection in adult and aged brains. The susceptibility can be enhanced by stimulation of neurogenesis. It was shown that latent murine CMV infection occurs in NSP cells by demonstrating the reactivation in brain slice culture or neurospheres. It is hypothesized that CMV brain disorder such as microcephaly is caused by disturbance of cellular events in the ventricular regions, including proliferation and differentiation of the neural stem cells, whereas neurons are also targets in persistent CMV infection, presumably resulting in functional disorders such as mental retardation.
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PMID:Roles of neural stem progenitor cells in cytomegalovirus infection of the brain in mouse models. 1842 23

Joubert syndrome (JS) is a developmental brain disorder characterized by cerebellar vermis hypoplasia, abnormal eye movement, ataxia and mental retardation. Mutations in CEP290 mutations are responsible for the cerebello-oculo-renal subtype of JS that includes kidney cysts and retinal degeneration, two phenotypes commonly linked to ciliopathies. CEP290 mutations are also associated with Meckel-Gruber syndrome and Bardet-Biedl syndrome (BBS). Here we demonstrate that CEP290 interacts with a centriolar satellite protein PCM-1, which is implicated in BBS4 function. CEP290 binds to PCM-1 and localizes to centriolar satellites in a PCM-1- and microtubule-dependent manner. The depletion of CEP290 disrupts subcellular distribution and protein complex formation of PCM-1. In accord with PCM-1's role in microtubule organization, CEP290 knockdown causes the disorganization of the cytoplasmic microtubule network. Moreover, we show that both CEP290 and PCM-1 are required for ciliogenesis and are involved in the ciliary targeting of Rab8, a small GTPase shown to collaborate with BBS protein complex to promote ciliogenesis. Our results suggest that PCM-1 is a potential mediator that may link CEP290 with BBS proteins in common molecular pathways.
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PMID:CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium. 1877 92

Congenital cytomegalovirus (CMV) infection is a significant cause of brain disorders, such as microcephaly, mental retardation, hearing loss and visual disorders in humans. The type and severity of brain disorder may be dependent on the stage of embryonic development when the congenital infection occurs. Developmental disorders may be associated with the type of embryonic cells to which CMV is susceptible and the effects of the infection on the cellular functions of these cells. Early murine embryos, including embryonic stem (ES) cells, are not susceptible to CMV infection. A part of the embryonic cells acquire susceptibility during early development. Mesenchymal cells are the targets of infection at midgestation, affecting organogenesis of the brain, eyes and oral-facial regions. In contrast to ES cells, neural stem progenitor cells (NSPC) from fetal brains are susceptible to murine CMV (MCMV) infection. The viral infection inhibits proliferation and differentiation of the NSPC to neuronal and glial cells in addition to induction of neuronal cell loss. These cellular events may cause brain malformations, such as microcephaly and polymicrogyria. Furthermore, MCMV persists in neuronal cells in developing brains, presumably resulting in neuronal dysfunction.
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PMID:Effects of cytomegalovirus infection on embryogenesis and brain development. 1948 54

Violence committed by acute psychiatric inpatients represents an important and challenging problem in clinical practice. Sociodemographic, clinical, and treatment information were collected for 1324 patients (677 men and 647 women) admitted to Italian public and private acute psychiatric inpatient facilities during an index period in 2004, and the sample divided into 3 groups: nonhostile patients (no episodes of violent behavior during hospitalization), hostile patients (verbal aggression or violent acts against objects), and violent patients (authors of physical assault). Ten percent (N = 129) of patients showed hostile behavior during hospitalization and 3% (N = 37) physically assaulted other patients or staff members. Variables associated with violent behavior were: male gender, <24 years of age, unmarried status, receiving a disability pension, having a secondary school degree, compulsory admission, hostile attitude at admission, and a diagnosis of schizophrenia, bipolar disorder, personality disorder, mental retardation, organic brain disorder or substance/alcohol abuse. Violent behavior during hospitalization was a predictive factor for higher Brief Psychiatric Rating Scale scores and for lower Personal and Social Performance scale scores at discharge. Despite the low percentage of violent and hostile behavior observed in Italian acute inpatient units, this study shed light on a need for the careful assessment of clinical and treatment variables, and greater effort aimed at improving specific prevention and treatment programs of violent behavior.
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PMID:Violent behavior in acute psychiatric inpatient facilities: a national survey in Italy. 1982 7

Mutations that diminish the function of the extracellular matrix receptor Dystroglycan (DG) result in muscular dystrophies, with associated neuronal migration defects in the brain and mental retardation e.g. Muscle Eye Brain Disease. To gain insight into the function of DG in the nervous system we initiated a study to examine its contribution to development of the eye of Drosophila melanogaster. Immuno-histochemistry showed that DG is concentrated on the apical surface of photoreceptors (R) cells during specification of cell-fate in the third instar larva and is maintained at this location through early pupal stages. In point mutations that are null for DG we see abortive R cell elongation during differentiation that first appears in the pupa and results in stunted R cells in the adult. Overexpression of DG in R cells results in a small but significant increase in their size. R cell differentiation defects appear at the same stage in a deficiency line Df(2R)Dg(248) that affects Dg and the neighboring mitochondrial ribosomal gene, mRpL34. In the adult, these flies have severely disrupted R cells as well as defects in the lens and ommatidia. Expression of an mRpL34 transgene rescues much of this phenotype. We conclude that DG does not affect neuronal commitment but functions R cell autonomously to regulate neuronal elongation during differentiation in the pupa. We discuss these findings in view of recent work implicating DG as a regulator of cell metabolism and its genetic interaction with mRpL34, a member of a class of mitochondrial genes essential for normal metabolic function.
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PMID:Dystroglycan and mitochondrial ribosomal protein L34 regulate differentiation in the Drosophila eye. 2046 73


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