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Notes: Abstract: ADP-ribosylation factors (ARFs) comprise a family of small GTP-binding proteins found in brain and other tissues. Recent studies have demonstrated that the expression of the larger heterotrimeric guanine nucleotide binding proteins is under control by steroid hormones. Therefore, in the present study, we examined the influence of glucocorticoids on the expression of ARF raRNA and protein, using specific cDNA probes and antisera, respectively. Chronic administration of corticosterone (7 days) significantly increased levels of mRNA for ARF1 and ARF3, two subtypes of ARF, in rat cerebral cortex. Chronic administration of corticosterone was also found to increase levels of ARF immunoreactivity in this brain region. However, 1-day administration of corticosterone did not influence levels of mRNA for either ARF1 or ARF3. In contrast to corticosterone, bilateral adrenalectomy (7 days after surgery) was found to decrease ARF1 and ARF3 message relative to sham controls; this effect of adrenalectomy was reversed by corticosterone treatment. These results demonstrate that the expression of ARF is under hormonal control and may underlie aspects of glucocorticoid action on neuronal function.

Notes: Using an antibody that recognizes the products of all known members of the fos family of immediate early genes, it was demonstrated that destruction of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle produces a prolonged (〉3 months) elevation of Fos-like immunoreactivity in the striatum. Using retrograde tract tracing techniques, we have previously shown that this increase in Foslike immunoreactivity is located predominantly in striatal neurons that project to the globus pallidus. In the present study, Western blots were performed on nuclear extracts from the intact and denervated striatum of 6-OHDA-lesioned rats to determine the nature of Fos-immunoreactive protein(s) responsible for this increase. Approximately 6 weeks after the 6-OHDA lesion, expression of two Fos-related antigens with apparent molecular masses of 43 and 45 kDa was enhanced in the denervated striatum. Chronic haloperidol administration also selectively elevated expression of these Fos-related antigens, suggesting that their induction after dopaminergic denervation is mediated by reduced activation of D2-like dopamine receptors. Western blot immunostaining using an antibody which recognizes the N-terminus of FosB indicated that the 43 and 45 kDa Fos-related antigens induced by dopaminergic denervation and chronic haloperidol administration may be related to a truncated from of FosB known as ΔFosB. Consistent with this proposal, retrograde tracing experiments confirmed that ΔFosB-like immunoreactivity in the deafferented striatum was located predominantly in striatopallidal neurons. Gel shift experiments demonstrated that elevated AP-1 binding activity in denervated striata contained FosB-like protein(s), suggesting that enhanced ΔFosB levels may mediate some of the effects of prolonged dopamine depletion on AP-1-regulated genes in striatopallidal neurons. In contrast, chronic administration of the D1-like receptor agonist CY 208–243 to 6-OHDA-lesioned rats dramatically enhanced ΔFosB-like immunoreactivity in striatal neurons projecting to the substantia nigra. Western blot immunostaining revealed that ΔFosB and, to a lesser extent, FosB are elevated by chronic D1-like agonist administration. Both the quantitative reverse transcriptase-polymerase chain reaction and the ribonuclease protection assay demonstrated that Δfos B mRNA levels were substantially enhanced in the denervated striatum by chronic D1-like agonist administration. Lastly, we examined the effects of chronic administration of D1-like and D2-like dopamine receptor agonists on striatal ΔFosB expression in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) primate model of Parkinson's disease. In monkeys rendered Parkinsonian by MPTP, there was a modest increase in ΔFosB-like protein(s), while the development of dyskinesia produced by chronic D1-like agonist administration was accompanied by large increases in ΔFosB-like protein(s). In contrast, administration of the long-acting D2-like agonist cabergoline, which alleviated Parkinsonian symptoms without producing dyskinesia reduced ΔFosB levels to near normal. Taken together, these results demonstrate that chronic alterations in dopaminergic neurotransmission produce a persistent elevation of ΔFosB-like protein(s) in both the rodent and primate striatum.

Notes: Summary Synapsin I (Protein I), a neuron-specific phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/ SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.

Notes: [Auszug] Members of the AP-1 family of transcription factors participate in the regulation of bone cell proliferation and differentiation. We report here a potent AP-1-related regulator of osteoblast function: ΔFosB, a naturally occurring truncated form of FosB that arises from alternative splicing ...

Notes: Abstract  Rationale: The NMDA antagonist MK-801 reportedly blocks experience-dependent changes in sensitivity to morphine, including tolerance to its analgesic actions and sensitization to its locomotor-stimulating effects. However, evidence in the existing literature suggests that some of MK-801’s effects are additive (or synergistic) with those of morphine. Objectives: Experiments were conducted to characterize the effects of acute and repeated administration of the combination of MK-801 and morphine on analgesia, locomotor activity, and drug discrimination in rats. Methods: In each experiment, rats were first tested repeatedly after treatment with the combination of MK-801 and morphine, and then after treatment with either drug alone. Results: The analgesic effects of MK-801 combined with morphine were greater than those of morphine alone, but tolerance to the combination of drugs developed at a similar rate as to morphine alone. The locomotor-stimulating effects of MK-801 combined with morphine were also greater than those of either drug alone, and locomotor sensitization developed to the combination of drugs but not to either drug alone at the low doses used. Rats learned to discriminate a combination of MK-801 and morphine from vehicle as quickly as they learned to discriminate morphine alone from vehicle, but those trained with the combination of MK-801 and morphine responded primarily at the vehicle-appropriate lever when given either drug alone. Conclusions: Since behavioral adaptations readily occur in the presence of MK-801, it appears that NMDA antagonists fail to invariably block the cellular plasticity that underlies such adaptations. Rather, the expression of adaptations in drug sensitivity appears related, at least in part, to the continued presence of the discriminative stimulus cues that are present during conditioning. Although NMDA receptors are important for some forms of cellular plasticity, the present studies illustrate the difficulty in interpreting behavioral studies in which MK-801 is given with morphine.