Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice infected with the LP-BM5 murine leukemia virus mixture develop severe immunosuppression and an encephalopathy characterized by spatial learning deficits. Twelve weeks after infection of C57BL/6J mice with LP-BM5, significant (50-60%) reductions in Met-enkephalin and substance P levels were observed in the striatum, whereas somatostatin levels were unchanged. In addition, a 39% decrease in hypothalamic substance P concentrations was observed, with no alteration in Metenkephalin levels. The apparent selectivity of the decrease in neuropeptide concentrations indicates that a functional alteration of the primary striatal efferent neurons occurs in this infection, which may contribute to the impairment of spatial learning observed in these mice. Moreover, this decrease in striatal neuropeptide levels is similar to the neuropathological changes in basal ganglia observed in HIV-infected individuals and is consistent with previous studies suggesting that the LP-BM5-infected mouse may serve as a useful model of AIDS dementia.
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PMID:Striatal met-enkephalin and substance P levels are decreased in mice infected with the LP-BM5 murine leukemia virus. 753 38

Progressive central nervous system dysfunction analogous to the AIDS dementia complex (ADC) seen in adults (HIV-1-associated progressive encephalopathy or HIV-1 encephalopathy) commonly occurs in HIV-1-infected children. The cause appears to be directly or indirectly related to HIV-1, rather than to other opportunistic pathogens. The exact mechanism(s) by which the virus affects brain function is not known. To determine whether the virus might modify brain function via an alteration in cortical neurons, we examined peptide neurotransmitter expression in the frontal cortex of HIV-1-infected cases with clinical HIV-1 encephalopathy relative to pathologic HIV-1 encephalitis. In situ hybridization was used to determine the level of peptide neurotransmitter expression of somatostatin in the frontal cortex of cases with and without HIV-1 encephalopathy and/or HIV-1 encephalitis. A 2-fold higher number of preprosomatostatin mRNA-positive interneurons was present in layer IV of cases with HIV-1 encephalitis compared with cases without HIV-1 encephalitis. In cases with PE, this neuronal alteration was 4- to 5-fold higher than in cases without PE, and was present in subcortical white matter in addition to layer IV. In cases having both PE and HIV-1 encephalitis, and in cases with HIV-1 encephalitis alone, these neuronal alterations in layer IV and/or subcortical white matter related to disseminated microglial nodules, even when these potentially viral-infected cells were negative for HIV-1 p24 antigen, a marker of productive viral infection. An alteration in preprosomatostatin mRNA-expressing cells occurring with HIV-1 encephalitis may be at least one mechanism that contributes to HIV-1 encephalopathy. When compared with other cortical laminae, layer IV receives most of its synaptic input from the mediodorsal nucleus of the thalamus. Neurons in the subcortical white matter project to the thalamus. The thalamus has been shown to have high amounts of viral antigen and increased metabolic activity in patients with AIDS. An alteration in preprosomatostatin mRNA-expressing cells may play a role in HIV-1 encephalopathy.
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PMID:A neuronal and neuroanatomical correlate of HIV-1 encephalopathy relative to HIV-1 encephalitis in HIV-1-infected children. 929 39

To gain insight into the neurochemical pathologies contributing to AIDS dementia complex, neurotransmitter levels were measured in the brains of mice infected with the LP-BM5 leukemia retrovirus. These mice develop immunologic and cognitive deficits analogous to human HIV-1 infection. Met-enkephalin and substance-P levels declined approximately 50% in the striatum and hypothalamus beginning as early as 4 weeks after infection. Hippocampal met-enkephalin levels were reduced to 50% only at 12 weeks after inoculation. Significant decreases (60-70%) in acetylcholine concentrations were observed in the striatum, cerebral cortex and hippocampus by 12 weeks after virus inoculation, while striatal GABA concentrations decreased to 50-60% at 8-12 weeks after infection. Striatal somatostatin levels were unchanged. Administration of the NMDA receptor antagonists MK-801 or LY 274614 ameliorated the decline in striatal met-enkephalin levels observed in mice after 8 weeks of infection. This pattern of neurotransmitter depletion and the ability of NMDA receptor antagonists to attenuate the loss of striatal met-enkephalin are consistent with an excitotoxic lesion. Thus, the elevation of glutamate levels secondary to glial activation may contribute to the contemporaneous development of cognitive deficits observed in mice infected with the LP-BM5 virus.
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PMID:The pattern of neurotransmitter alterations in LP-BM5 infected mice is consistent with glutamatergic hyperactivation. 963 May 62