Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine what contributions are made to the rat full-field electroretinogram (ERG) by ganglion cells (GCs). To that end, the ERG was assessed longitudinally following optic nerve transection (ONTx). Additional studies were conducted using intravitreal injections of pharmacologically active substances. The ERG was recorded simultaneously from both eyes of anaesthetized adult Brown-Norway rats (ketamine: xylazine: acepromazine, 55: 5: 1 mg kg(-1)) using custom silver chloride electrodes. Stimuli were brief, white xenon discharges delivered via a Ganzfeld under dark-adapted and light-adapted conditions (150 cd m(-2)). ERGs were obtained 1, 2, 3, 4 and 9 weeks after ONTx (n = 8) or sham (n = 8) operations. ONTx reduced both positive and negative components of the scotopic threshold response (pSTR and nSTR). Scotopic ERG responses to brighter flashes, including a-waves, b-waves and oscillatory potentials (OPs) were unaffected by ONTx. ONTx reduced the photopic b-wave and OPs. TTX (6 microM) reduced the pSTR and nSTR, but not the scotopic a-wave, b-wave or OPs. TTX had dramatic effects on the photopic ERG, surpassing the effects of ONTx. TTX application 9 weeks post-ONTx had little additional effect on the STR. Inhibition of inner retinal responses using GABA (10 mM) or NMDA (0.8 mM) reduced the nSTR substantially. Similar results were obtained with antagonists of AMPA/KA ionotropic glutamate receptors 6-cyano-7-nitroquinoxaline-2,3(1H,4H)-dione (CNQX, 0.2 mM) or cis-2,3-piperidinedicarboxylic acid (PDA, 5 mm); however, both also reduced the scotopic b-wave by approximately 40 %. By contrast, the NMDA receptor antagonist D(-)-2-amino-7-phosphonoheptanoic acid (D-AP7, 0.2 mM) had no effect alone, but the combination of D-AP7 and CNQX completely abolished the STR. The results of this study indicate that: (1) both pSTR and nSTR components in the rat depend directly upon intact GC responses, and that amacrine cell contributions to these components are relatively small; (2) scotopic ERG response components to brighter flashes receive little influence from GCs; (3) the rat photopic ERG also reflects GC signals and may serve as an additional useful test of GC function; (4) TTX had dramatic effects on the rat photopic ERG that were not attributable to GC currents, but rather to voltage-gated sodium currents in amacrine or interplexiform cells; (5) a small residual negative STR persisted after ONTx that was likely to be generated by graded responses of third-order retinal cells, most likely amacrine cells.
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PMID:Ganglion cell contributions to the rat full-field electroretinogram. 1457 84

Using quantitative receptor autoradiography, we assessed binding site densities and distribution patterns of glutamate, GABA(A), acetylcholine (ACh), and monoamine receptors in the hippocampus of 32-month-old Fischer 344/Brown Norway rats. Prior to autoradiography, the rats were divided into two groups according to their retention performance in a water maze reference memory task, which was assessed 1 week after 8 days of daily maze training. The animals of the inferior group showed less long-term retention of the hidden-platform task but did not differ from superior rats in their navigation performance during place training and cued trials. The decreased retention performance in the group of inferior learners was primarily accompanied by increased alpha(1)-adrenoceptors in all hippocampal subregions under inspection (CA1-CA4 and dentate gyrus), while elevated alpha(2)-adrenoceptor binding was observed in the CA1 region and DG. Furthermore, inferior learners had higher NMDA binding in the CA2 and CA4 and increased 5-HT(1A) binding sites in the CA2, CA3, and CA4 region. No significant differences between inferior and superior learners were evident with regard to AMPA, kainate, GABA(A), muscarinergic M(1), dopamine D(1), and 5-HT(2) binding densities in any hippocampal region analyzed. These results show that increased NMDA, 5-HT(1A), and alpha-adrenoceptor binding in the hippocampus is associated with a decline in spatial memory. The increased receptor binding observed in the group of old rats with inferior maze performance might be the result of neural adaptation triggered by age-related changes in synaptic connectivity and/or synaptic activity.
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PMID:Impaired maze performance in aged rats is accompanied by increased density of NMDA, 5-HT1A, and alpha-adrenoceptor binding in hippocampus. 1711 11

Whole-brain irradiation is used for the treatment of brain tumors, but can it also induce neural changes, with progressive dementia occurring in 20-50% of long-term survivors. The present study investigated whether 45 Gy of whole-brain irradiation delivered to 12-month-old Fischer 344 x Brown Norway rats as nine fractions over 4.5 weeks leads to impaired Morris water maze (MWM) performance 12 months later. Compared to sham-irradiated rats, the irradiated rats demonstrated impaired MWM performance. The relative levels of the NR1 and NR2A but not the NR2B subunits of the NMDA receptor were significantly higher in hippocampal CA1 of irradiated rats compared to control rats. No significant differences were detected for these NMDA subunits in CA3 or dentate gyrus. Further analysis of CA1 revealed that the relative levels of the GluR1 and GluR2 subunits of the AMPA receptor and synaptophysin were not altered by whole-brain irradiation. In summary, a clinically relevant regimen of fractionated whole-brain irradiation led to significant impairments in spatial learning and reference memory and alterations in the relative levels of subunits of the NMDA, but not the AMPA, receptors in hippocampal CA1. These findings suggest for the first time that radiation-induced cognitive impairments may be associated with alterations in glutamate receptor composition.
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PMID:Spatial learning and memory deficits after whole-brain irradiation are associated with changes in NMDA receptor subunits in the hippocampus. 1714 74

Caloric restriction (CR) attenuates aging-related degenerative processes throughout the body. It is less clear, however, whether CR has a similar effect in the brain, particularly in the hippocampus, an area important for learning and memory processes that often are compromised in aging. In order to evaluate the effect of CR on synapses across lifespan, we quantified synapses stereologically in the middle molecular layer of the dentate gyrus (DG) of young, middle aged and old Fischer 344 x Brown Norway rats fed ad libitum (AL) or a CR diet from 4 months of age. The results indicate that synapses are maintained across lifespan in both AL and CR rats. In light of this stability, we addressed whether aging and CR influence neurotransmitter receptor levels by measuring subunits of NMDA (NR1, NR2A and NR2B) and AMPA (GluR1, GluR2) receptors in the DG of a second cohort of AL and CR rats across lifespan. The results reveal that the NR1 and GluR1 subunits decline with age in AL, but not CR rats. The absence of an aging-related decline in these subunits in CR rats, however, does not arise from increased levels in old CR rats. Instead, it is due to subunit decreases in young CR rats to levels that are sustained in CR rats throughout lifespan, but that are reached in AL rats only in old age.
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PMID:Effects of aging and caloric restriction on dentate gyrus synapses and glutamate receptor subunits. 1743 2