Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Catecholaminergic (presumed dopaminergic) amacrine cells in the retinae of Beagle dogs (canis lupus f. familiaris) and wolves (canis lupus) were visualized with an antiserum against tyrosine hydroxylase (TH). In both species, TH immunoreactivity is found in a population of amacrine cells with large somata (about 14 microns diameter) and large, moderately branched dendritic trees. Somata are located in the proximal inner nuclear layer (normal amacrines) or in the ganglion cell layer (displaced amacrines). Most dendrites stratify in a narrow band in the inner plexiform layer close to the inner nuclear layer, where they form a dense plexus with the characteristic pattern of "dendritic rings." The displaced cells have some of their dendrites in a proximal stratum of the inner plexiform layer. A few immunopositive processes are found in the outer plexiform layer (interplexiform processes). In Beagle dogs, the cell density of catecholaminergic amacrines varies from less than 1/mm2 in far periphery to 40-55/mm2 in central retina (mean density 21/mm2). The proportion of displaced amacrines varies locally from 10 to 85% (overall proportion 41% in one retina). In the wolf, densities of catecholaminergic cells range between about 3/mm2 in peripheral and up to 35/mm2 in central retina. The proportion of displaced cells is somewhat lower than in dogs, varying between 11 and 31% across the retina. The morphology and density distribution of canine catecholaminergic amacrines resemble that of other mammalian retinae. A marked difference, however, is the high percentage of displaced cells in both dog and wolf retina; it is the highest found in any mammal so far. The displaced and normal cells appear to be members of a single functional population. A comparison of the topographic distributions of catecholaminergic amacrines, rods, and ganglion cells in the dog retina shows no consistent density correlations between these neurons that are all part of the rod pathway.
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PMID:Catecholaminergic amacrine cells in the dog and wolf retina. 168 28

Environmental enrichment has been shown to be both neuroprotective and neurorestorative in 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of Parkinson's disease (PD). However, whether social interaction or novel physical stimulation is responsible for this recovery is controversial. In the current study, we have investigated the effects of only social enrichment (SocE) in progressively MPTP-lesioned mice. After mice were lesioned using a progressively increased dose (4 mg/kg, 8 mg/kg, 16 mg/kg and 32 mg/kg; each dose daily for 5 days), the MPTP-induced behavioral deficits, after the 32 mg/kg dose, were reversed with acute L-DOPA. This acute behavioral recovery suggests that this progressive MPTP-induced neurodegeneration is an appropriate murine model of PD. Mice were housed four per cage for the first 2 weeks of progressive lesioning or vehicle treatment. After the 8 mg/kg MPTP dose (prior to SocE intervention) mice showed a significant decrease in rearing and foot fault behaviors (FF/BB) compared to the vehicle group. Additionally, there was a 38% decrease in mean number of tyrosine hydroxylase immunoreactive (TH-ir) substantia nigra pars compacta (SNpc) neurons/section, and a 50% decrease in the optical density of TH-ir dorsolateral caudate putamen (CPu) terminals compared to the vehicle group. Mice were then housed either two (socially limited environment; SLE) or twelve (SocE) mice per cage during continued MPTP lesioning for the next 2 weeks at 16 mg/kg and 32 mg/kg MPTP. MPTP treatment was then discontinued, while mice remained in the SLE or SocE cages for an additional week. Rearing behavior was further impaired in SLE-MPTP mice following progressive MPTP, accompanied by additional decreases in the mean number of TH-ir SNpc neurons/section and CPu TH-ir terminals. CPu TH and dopamine transporter (DAT) protein expression, as well as dopamine tissue and TH protein levels was significantly decreased compared to either vehicle group. However, the deficit in rearing behavior in SLE-MPTP mice was reversed with acute L-DOPA following the intervention period. SocE-MPTP mice showed rearing and FF/BB behaviors similar to vehicle levels, although FF/BB was not significantly different from pre-intervention levels. The reversal from pre-intervention rearing deficits was correlated with an attenuated decrease in the mean number of SNpc TH-ir neurons/section and CPu TH and DAT protein, and with a blocked decrease in CPu TH-ir terminals compared to pre-intervention levels. Our findings show that SocE mice not only resist further nigrostriatal lesioning and FF/BB deficit, but rearing behavior is recovered to the level of the vehicle group despite continued MPTP treatment. In contrast, SLE mice showed continued loss of nigrostriatal TH-ir and decline of motor behaviors with progressive MPTP. The data suggest that non-pharmacological intervention that started at an early stage of dopamine loss is effective at slowing or blocking further nigrostriatal degeneration.
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PMID:Social enrichment attenuates nigrostriatal lesioning and reverses motor impairment in a progressive 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. 2219 3

While some autoimmune disorders remain extremely rare, others largely predominate the epidemiology of human autoimmunity. Notably, these include psoriasis, diabetes, vitiligo, thyroiditis, rheumatoid arthritis and multiple sclerosis. Thus, despite the quasi-infinite number of "self" antigens that could theoretically trigger autoimmune responses, only a limited set of antigens, referred here as superautoantigens, induce pathogenic adaptive responses. Several lines of evidence reviewed in this paper indicate that, irrespective of the targeted organ (e.g. thyroid, pancreas, joints, brain or skin), a significant proportion of superautoantigens are highly expressed in the synaptic compartment of the central nervous system (CNS). Such an observation applies notably for GAD65, AchR, ribonucleoproteins, heat shock proteins, collagen IV, laminin, tyrosine hydroxylase and the acetylcholinesterase domain of thyroglobulin. It is also argued that cognitive alterations have been described in a number of autoimmune disorders, including psoriasis, rheumatoid arthritis, lupus, Crohn's disease and autoimmune thyroiditis. Finally, the present paper points out that a great majority of the "incidental" autoimmune conditions notably triggered by neoplasms, vaccinations or microbial infections are targeting the synaptic or myelin compartments. On this basis, the concept of an immunological homunculus, proposed by Irun Cohen more than 25 years ago, is extended here in a model where physiological autoimmunity against brain superautoantigens confers both: i) a crucial evolutionary-determined advantage via cognition-promoting autoimmunity; and ii) a major evolutionary-determined vulnerability, leading to the emergence of autoimmune disorders in Homo sapiens. Moreover, in this theoretical framework, the so called co-development/co-evolution model, both the development (at the scale of an individual) and evolution (at the scale of species) of the antibody and T-cell repertoires are coupled to those of the neural repertoires (i.e. the distinct neuronal populations and synaptic circuits supporting cognitive and sensorimotor functions). Clinical implications and future experimental insights are also presented and discussed.
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PMID:Evolution, immunity and the emergence of brain superautoantigens. 2852 99