Biomedical subjects

H S Oliff

Publications and source records attributed to H S Oliff.

8 recordsLinked to original sources

PubMed1999

The effect of nicotine on developing brain catecholamine systems.

Biochemical studies have confirmed that nicotinic acetylcholine receptor mRNA and protein are expressed early in the development of the fetal central nervous system. Perinatal administration of nicotine produces a broad spectrum of effects on brain development, including inhibition of DNA synthesis, altered ornithine decarboxylase activity, altered neurotransmitter function, and significant alterations in cortical morphogenesis. Catecholamine systems, both in the brain and in the periphery, are particularly sensitive to prenatal nicotine exposure. Acute and chronic nicotine administered to pregnant dams causes alterations in dopamine and its metabolites in male and female rat fetuses. These changes can persist into adulthood. Prenatal nicotine exposure also causes locomotor disturbances in pups, which can have long-lasting effects. The effect of nicotine on developing noradrenergic neurons is less clear. Some effects may include increases in noradrenergic neuronal activity in the pup and aberrant central release of norepinephrine in response to neonatal hypoxia after nicotine exposure in utero. Catecholamine neurons develop early in ontogeny, so nicotine induced alterations have the potential to induce permanent changes. Hence, more research is needed to get a clearer picture of the effect of nicotine on developing catecholamine systems. The affects of nicotine on catecholamine systems in the adult are discussed for comparison.

Animals↗

PubMed1999

Hippocampal BDNF mRNA shows a diurnal regulation, primarily in the exon III transcript.

Endogenous expression levels of brain-derived neurotrophic factor (BDNF) mRNA were assessed using in situ hybridization to investigate whether there is a natural diurnal fluctuation in BDNF mRNA expression in the hippocampus of rats housed with a normal (12:12 h) light/dark cycle. BDNF expression was increased during lights out (dark-cycle) to 134%-158% of light-cycle levels in hippocampal regions CA1, CA3, and hilus. In addition, expression levels of the four BDNF transcript forms, exons I-IV, were assessed to evaluate whether expression of specific BDNF transcripts exhibited differential endogenous fluctuation. All exons had lowest levels of expression at either noon or 6 p.m. Significant correlations were found between exon expression level and time, with elevated expression occurring at dark-cycle timepoints. The exon III transcript showed the greatest diurnal change in expression in all hippocampal fields, with dark-cycle expression elevated to 219-419% of light-cycle expression level. In addition to exon III, dark-cycle exon II mRNA levels were elevated in all hippocampal subfields, to 140-180% of light-cycle levels, suggesting that the endogenous fluctuation in BDNF expression results predominantly from activation of the promoters linked to exons II and III. Previously we have shown that physical activity increases BDNF expression. The naturally occurring rise in BDNF expression during the dark-cycle, the time when rats are most physically active, may be due to increased activity and arousal levels. Because BDNF has a role in plasticity, the increase in BDNF expression during the time that a rat is maximally interacting with its surroundings may be part of an ongoing stimulus-encoding mechanism, or may be a mechanism to maximize information storage about the environment.

Analysis of Variance↗

PubMed1998

Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus.

Previous results from our laboratory indicate that two nights of voluntary wheel running upregulates brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. In order to investigate the time-course of the BDNF response and to examine how physical activity preferentially activates particular transcriptional pathways, the effects of 6 and 12 h of voluntary wheel running on BDNF and exons I-IV mRNA expression were investigated in rats. Hippocampal full-length BDNF mRNA expression was rapidly influenced by physical activity, showing significant increases in expression levels as soon as 6 h of voluntary wheel running. Moreover, there was a strong positive correlation between distance run and BDNF mRNA expression. Exon I mRNA expression was significantly upregulated after 6 h of running and was maintained or enhanced by 12 h of voluntary running. Exon II had a slower time-course and was significantly upregulated after 12 h, selectively in the CA1 hippocampal region. Exon III and Exon IV showed no significant increase in expression level after 6 or 12 h of running in the paradigm studied. It is significant that the rapid neurotrophin response is demonstrated for a physiologically relevant stimulus, as opposed to the extreme conditions of seizure paradigms. Furthermore, exercise-induced upregulation of BDNF may help increase the brain's resistance to damage and neurodegeneration that occurs with aging.

Animals↗

PubMed1997

Rat strain and vendor differences in collateral anastomoses.

Recently we observed inter- and intrastrain differences in cortical infarct volumes after middle cerebral artery (MCA) occlusion. Variations in the anastomoses providing collateral blood supply could account for different lesion sizes. Our objectives were to compare number and internal diameters of the MCA-anterior cerebral artery (MCA-ACA) anastomoses and to determine if the lesion extended beyond branches of the MCA territory into the field of the ACA in the rat strains/lines. Sprague-Dawley rats and Wistar rats from Simonsen Laboratories (SLSD and SLWIS) and Sprague-Dawley rats from Taconic Laboratories (TLSD) and Charles River Laboratories (CRSD) were anesthetized and injected with papaverine and Vultex (white latex) for arterial visualization. Some rats were also subjected to MCA occlusion. Significantly fewer anastomoses were present in SLSD and SLWIS than in CRSD and TLSD (p < 0.05). The mean internal diameters of the anastomoses were not significantly different between the strains/lines (p < 0.05). After MCA occlusion, significantly more (p < 0.05) TLSD and CRSD than SLSD had lesions extending from the MCA field beneath the anastomoses and into the region supplied by the ACA. Neither the number, luminal diameter, nor density of MCA-ACA anastomoses appears to be the limiting factor that differentiates lesion size following MCA occlusion in these particular rat strains/lines. Therefore, factors other than anatomical variations probably account for different lesion sizes.

Animals↗

PubMed1996

The neuroprotective efficacy of MK-801 in focal cerebral ischemia varies with rat strain and vendor.

The present study was designed to evaluate whether the neuroprotective efficacy of MK-801 in focal cerebral ischemia was dependent on strain and/or vendor differences. MK-801 (0.12 mg/kg i.v. bolus followed by 0.108 mg/kg/h infusion or 0.60 mg/kg i.v. bolus followed by 0.540 mg/kg/h infusion) or saline was administered just after intraluminal middle cerebral artery occlusion. Administration of 0.540 mg/kg/h MK-801 provided strain/line-dependent neuroprotection in the following rank order: Simonsen Laboratories Sprague-Dawley rats > Simonsen Laboratories Wistar rats > Taconic Laboratories Sprague-Dawley rats. After 0.108 mg/kg/h MK-801 treatment, Simonsen Laboratories Wistar rats were the only strain/line that were significantly neuroprotected. These results indicate that the neuroprotective effect of an experimental drug may be influenced by rat strain and vendor differences.

Animals↗

PubMed1996

The quaternary transformation products of N-(3-chloropropyl)-4-piperidinyl diphenylacetate and N-(2-chloroethyl)-4-piperidinyl diphenylacetate (4-DAMP mustard) have differential affinity for subtypes of the muscarinic receptor.

A 3-chloropropylamine derivative (N-(3-chloropropyl)-4-piperidinyl diphenylactate) of the selective muscarinic antagonist N,N-dimethyl-4-piperidinyl diphenylacetate was synthesized and its conversion to a stable azetidinium ion and interaction with muscarinic receptors was investigated. When dissolved in aqueous solution at pH 7.4, N-(3-chloropropyl)-4-piperidinyl diphenylactate formed a stable azetidinium ion with a half-time of approximately 3.6 hr. The selectivity of the azetidinium ion for native M1, M2 and M3 subtypes of the muscarinic receptors was investigated in competitive binding experiments on the hippocampus, heart and submaxillary gland of rats, respectively, using N-[3H]methylscopolamine as the radioligand. The azetidinium ion exhibited equivalent high affinities for the M1 and M3 mucarinic receptor subtypes (KD = approximately 5 nM), but 10-fold lower affinity for the M2 muscarinic receptor subtype (KD = 44 nM). Similar competitive binding experiments were carried out on Chinese hamster ovary cells transfected with the M1 through M5 subtypes of the muscarinic receptor. In these experiments, the azetidinium ion exhibited similar high affinities for the M1, M3, M4 and M5 muscarinic receptor subtypes (KD = approximately 2.4 nM), but approximately 14-fold lower affinity for the M2 muscarinic receptor subtype (KD = 34 nM). In contrast to the azetidinium ion, the parent N-(3-chloropropyl)-4-piperidinyl diphenylactate compound was 130-fold less potent. An analogous series of experiments were carried out with the aziridinium ion derived from the muscarinic receptor alkylating agent, N-(2-chloroethyl)-4-piperidinyl diphenylactate. For these binding experiments, the incubations were carried out at 0 degrees C to prevent the aziridinium ion from alkylating muscarinic receptors. The aziridinium ion was found to have equivalent high affinities for the M1, M3, M4 and M5 subtypes of the muscarinic receptor (KD = approximately 6.6 nM), but about 11-fold lower affinity for the M2 muscarinic receptor subtype (KD = 72 nM). Our results suggest that 3-haloalkylamine derivatives of 4-piperidinyl diphenylactate may be candidate prodrugs that may penetrate into brain and form azetidinium ions that have a long-lasting central anticholinergic effect.

Animals↗

PubMed1995

Infarct volume varies with rat strain and vendor in focal cerebral ischemia induced by transcranial middle cerebral artery occlusion.

We recently reported that the outcome of focal cerebral ischemia induced by intraluminal middle cerebral artery occlusion may differ depending upon a rat's strain and/or vendor. Sprague-Dawley rats originating from Taconic Laboratories and Charles River Laboratories had infarct volumes several fold larger than Sprague-Dawley rats originating from Simonsen Laboratories. The present study sought to determine whether these differences were restricted to an intraluminal technique or whether strain and vendor dependent differences will also exist in rats subjected to a transcranial method of focal cerebral ischemia. Accordingly, we permanently coagulated the middle cerebral artery via a transcranial approach in Sprague-Dawley rats originating from Simonsen Laboratories and Taconic Laboratories and in Simonsen Laboratories Fischer-344 rats. The cortical infarct volume significantly differed in the following order: Simonsen Laboratories Sprague-Dawley rats < Simonsen Laboratories Fischer-344 rats < Taconic Laboratories Sprague-Dawley rats. The subcortical infarct volume differed statistically in the following order: Simonsen Laboratories Sprague-Dawley rats < Taconic Laboratories Sprague-Dawley rats < Simonsen Laboratories Fischer-344 rats. These results along with our previous findings demonstrate that strain and vendor differences in the outcome of focal cerebral ischemia are independent of the technique applied.

Animals↗

PubMed1995

The role of strain/vendor differences on the outcome of focal ischemia induced by intraluminal middle cerebral artery occlusion in the rat.

This study investigated the role of strain and vendor differences on the outcome of focal cerebral ischemia in the rat induced by occlusion of the middle cerebral artery by an intraluminal thread. The cortical infarct volumes (Mean +/- S.E.M.) were: 14.2 +/- 6.2 mm3 in Simonsen Laboratories Sprague-Dawley rats; 84.0 +/- 22.9 mm3 in Simonsen Laboratories Wistar rats; 223.3 +/- 23.6 mm3 in Taconic Laboratories Sprague-Dawley rats; and 239.5 +/- 30.7 mm3 in Charles River Laboratories Sprague-Dawley rats. Middle cerebral artery occlusion combined with bilateral common carotid artery occlusion for 60 min increased cortical infarct volumes to: 113.0 +/- 18.8 mm3; 152.4 +/- 21.1 mm3; 227.8 +/- 19.3 mm3; and 248.4 +/- 24.0 mm3, respectively. To control the effect of blood pressure as a variable contributing to the outcome of ischemia, additional experiments where performed in which the blood pressure in Simonsen Laboratories Sprague-Dawley rats was lowered to the level of the blood pressure in Taconic Laboratories Sprague-Dawley rats. Although this manipulation increased the cortical infarct volumes in Simonsen Laboratories Sprague-Dawley rats, the volumes were still less than those in Taconic Laboratories Sprague-Dawley rats. The results of the present study indicate that the outcome of ischemia in the intraluminal thread model may dramatically differ depending on the strain and vendor of animal used.

Animals↗