Biomedical subjects

Camille S Norton

Publications and source records attributed to Camille S Norton.

6 recordsLinked to original sources

PubMed2005

Cellular DNA content parameters as prognostic indicators in human astrocytomas.

OBJECTIVE: Clinical parameters such as grade, size and/or location of the tumor are good predictors of outcome in patients with astrocytoma. The objective of this study was to determine whether DNA content parameters have a prognostic significance for this group of tumors. METHODS: Following optimization and validation of methodology for evaluating cellular DNA content parameters (CDCP), tumor DNA ploidy and percent S phase fraction (SPF) were determined from 64 patients using formalin fixed, paraffin embedded specimens (mean coefficient of variation=4.94) obtained over a 10-year period. Median survival times correlated with grade (I/II=1154 vs. III/IV=483days, P=0.0317). Fifty-five percent of the specimens contained DNA aneuploid (DNA-A) components (average SPF=18.3%) and 45% were DNA diploid (DNA-D) (average SPF=9.6%). Survival did not correlate with overall differences in DNA ploidy (DNA-D=181 vs. DNA-A=206days, P=0.6314) when treated and untreated tumors were analyzed. However, a trend for prolonged median survival was observed in patients whose tumors were untreated with respect to cytotoxic therapy based on DNA ploidy status (DNA-D=275 vs. DNA-A=15days, P=0.3408). Survival for all patients did not correlate with median SPF (<13.5% av.=121 vs. >13.5% av.=154days, P=0.6534). CONCLUSION: DNA content parameters may correlate with the natural history and treatment outcome of newly diagnosed untreated patients with astrocytomas.

Adult↗

PubMed2004

Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia.

BACKGROUND: Alterations of serotonin neurotransmission are implicated in both mood disorders and schizophrenia. Specific serotonin-receptor-based abnormalities in these psychiatric illnesses have been intensively studied; however, it has been difficult to draw any conclusions because of a lack of consensus. These inconsistencies have most likely arisen from the unavailability of selective ligands. METHODS: Our study used in situ hybridization to quantify 5-HT(1A), 5-HT(1B), and 5-HT(2A) mRNA levels in the hippocampus (HC) and 5-HT(1A) and 5-HT(2A) mRNA levels in the dorsolateral prefrontal cortex (DLPFC) of subjects with a history of major depression disorder (MDD), bipolar disorder (BPD), schizophrenia, and a normal comparison group (15 subjects per group). RESULTS: In the DLPFC, there is a significant decrease in 5-HT(1A) mRNA of subjects with MDD and in 5-HT(2A) mRNA of subjects with BPD. Subjects with MDD have a significant decrease in 5-HT(1A) mRNA in the HC; subjects with BPD and schizophrenia had increased 5-HT(1B) mRNA levels and a significant decrease in 5-HT(2A) mRNA levels in the hippocampal formation. CONCLUSIONS: Alterations in 5-HT(1A,) 5-HT(1B), and 5-HT(2A) mRNA levels in the brains of subjects with both mood disorders and schizophrenia add further support for hypothesis of dysregulation of the serotonergic system in these psychiatric disorders.

Adult↗

PubMed2003

Amphetamine-induced c-fos mRNA expression in the caudate-putamen and subthalamic nucleus: interactions between dose, environment, and neuronal phenotype.

When administered in a novel environment relatively low doses of amphetamine induce c-fos mRNA in the subthalamic nucleus (STN) and in preproenkephalin mRNA-containing (ENK+) neurons in the caudate-putamen (CPu). When administered at home, however, low doses of amphetamine do not produce these effects. Environmental novelty also facilitates the behavioral effects of acute and repeated amphetamine, but this is dose-dependent. The purpose of the present experiment therefore was to determine if the effect of context on amphetamine-induced c-fos expression is also dose-dependent. It was found that: (i) No dose of amphetamine tested (1-10 mg/kg) induced c-fos in many ENK+ cells when given at home. (ii) When given in a novel environment low to moderate doses of amphetamine (1-5 mg/kg) induced c-fos in substantial numbers of ENK+ cells, but the highest dose examined (10 mg/kg) did not. (iii) Environmental novelty enhanced the ability of low to moderate doses of amphetamine to induce c-fos in the STN, but the highest dose of amphetamine induced robust c-fos mRNA expression in the STN regardless of context. The results do not support the idea that engaging ENK+ cells, at least as indicated by c-fos mRNA expression, is critical to produce robust behavioral sensitization, but do suggest a possible role for the STN. Furthermore, the results highlight the importance of drug-environment interactions on the neurobiological effects of drugs, and have implications for thinking about the circuits by which context modulates the acute and long-lasting consequences of amphetamine treatment.

Amphetamine↗

PubMed2003

Amphetamine-evoked c-fos mRNA expression in the caudate-putamen: the effects of DA and NMDA receptor antagonists vary as a function of neuronal phenotype and environmental context.

Dopamine (DA) and glutamate neurotransmission is thought to be critical for psychostimulant drugs to induce immediate early genes (IEGs) in the caudate-putamen (CPu). We report here, however, that the ability of DA and glutamate NMDA receptor antagonists to attenuate amphetamine-evoked c-fos mRNA expression in the CPu depends on environmental context. When given in the home cage, amphetamine induced c-fos mRNA expression predominately in preprodynorphin and preprotachykinin mRNA-containing neurons (Dyn-SP+ cells) in the CPu. In this condition, all of the D1R, D2R and NMDAR antagonists tested dose-dependently decreased c-fos expression in Dyn-SP+ cells. When given in a novel environment, amphetamine induced c-fos mRNA in both Dyn-SP+ and preproenkephalin mRNA-containing neurons (Enk+ cells). In this condition, D1R and non-selective NMDAR antagonists dose-dependently decreased c-fos expression in Dyn-SP+ cells, but neither D2R nor NR2B-selective NMDAR antagonists had no effect. Furthermore, amphetamine-evoked c-fos expression in Enk+ cells was most sensitive to DAR and NMDAR antagonism; the lowest dose of every antagonist tested significantly decreased c-fos expression only in these cells. Finally, novelty-stress also induced c-fos expression in both Dyn-SP+ and Enk+ cells, and this was relatively resistant to all but D1R antagonists. We suggest that the mechanism(s) by which amphetamine evokes c-fos expression in the CPu varies depending on the stimulus (amphetamine vs. stress), the striatal cell population engaged (Dyn-SP+ vs. Enk+ cells), and environmental context (home vs. novel cage).

Amphetamine↗

PubMed2002

Nociceptin/orphanin FQ and opioid receptor-like receptor mRNA expression in dopamine systems.

Although nociceptin/orphanin FQ (N/OFQ) influences dopamine (DA) neuronal activity, it is not known whether N/OFQ acts directly on DA neurons, indirectly by means of local circuitry, or both. We used two parallel approaches, dual in situ hybridization (ISH) and neurotoxic lesions of DA neurons by using 6-hydroxydopamine (6-OHDA), to ascertain whether N/OFQ and the N/OFQ receptor (NOP) mRNA are expressed in DA neurons in the ventral tegmental area (VTA) and substantia nigra compacta (SNc). In the VTA and SNc, small populations (approximately 6-10%) of N/OFQ-containing neurons coexpressed mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis. Similarly, very few (1-2%) TH-positive neurons contained N/OFQ mRNA signal. A majority of NOP-positive neurons (approximately 75%) expressed TH mRNA and roughly half of the TH-containing neurons expressed NOP mRNA. Many N/OFQ neurons (approximately 50-60%) expressed glutamic acid decarboxylase 65 and 67 mRNAs, markers for gamma-aminobutyric acid (GABA) neurons. In the 6-OHDA lesion studies, NOP mRNA levels were nearly 80 and 85% lower in the VTA and SNc, respectively, on the lesioned side. These lesions appear to lead to compensatory changes, with N/OFQ mRNA levels approximately 60% and 300% higher in the VTA and SNc, respectively, after 6-OHDA lesions. Finally, N/OFQ-stimulated [(35)S]guanylyl-5'-O-(gamma-thio)-triphosphate levels were decreased in the VTA and SNc but not the prefrontal cortex after 6-OHDA lesions. Accordingly, it appears that N/OFQ mRNA was found largely on nondopaminergic (i.e., GABA) neurons, whereas NOP mRNA was located on DA neurons. N/OFQ is in a position to influence DA neuronal activity by means of the NOP located on DA neurons.

Animals↗

PubMed2002

The ability of amphetamine to evoke arc (Arg 3.1) mRNA expression in the caudate, nucleus accumbens and neocortex is modulated by environmental context.

The ability of amphetamine or cocaine to induce the expression of c-fos mRNA in a number of brain regions is greatly enhanced when these drugs are administered in a distinct and relatively novel environment, relative to when they are given in the home cage. The purpose of this study was to determine if environmental context has a similar effect on the ability of amphetamine to induce the expression of arc (also known as Arg 3.1), an "effector" immediate early gene (IEG) thought to play a direct role in cellular plasticity. Rats were administered either saline or amphetamine (0.5 mg/kg, i.v.), in their home cage or in a distinct test environment. Fifty minutes later, they were decapitated and their brains processed for in situ hybridization histochemistry. In the prefrontal cortex, caudate-putamen and core of the nucleus accumbens, amphetamine significantly increased arc mRNA expression under both conditions, but the level of expression was significantly enhanced when amphetamine was given in a distinct environment. In the shell of the nucleus accumbens amphetamine significantly increased the expression of arc mRNA only when it was administered in the distinct environment. Thus, the ability of amphetamine to induce the expression of arc varies as a function of the environmental context in which it is administered. This could contribute to the ability of environmental context to modulate forms of drug experience-dependent neuroplasticity, including behavioral sensitization.

Amphetamine↗