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Biomedical subjects

D MacTavish

Publications and source records attributed to D MacTavish.

8 recordsLinked to original sources
PubMed2001

Cellular mechanisms for amyloid beta-protein activation of rat cholinergic basal forebrain neurons.

The deposition of amyloid beta-protein (Abeta) in the brain and the loss of cholinergic neurons in the basal forebrain are two pathological hallmarks of Alzheimer's disease (AD). Although the mechanism of Abeta neurotoxicity is unknown, these cholinergic neurons display a selective vulnerability when exposed to this peptide. In this study, application of Abeta(25-35) or Abeta(1-40) to acutely dissociated rat neurons from the basal forebrain nucleus diagonal band of Broca (DBB), caused a decrease in whole cell voltage-activated currents in a majority of cells. This reduction in whole cell currents occurs through a modulation of a suite of potassium conductances including calcium-activated potassium (I(C)), the delayed rectifier (I(K)), and transient outward potassium (I(A)) conductances, but not calcium or sodium currents. Under current-clamp conditions, Abeta evoked an increase in excitability and a loss of accommodation in cholinergic DBB neurons. Using single-cell RT-PCR technique, we determined that Abeta actions were specific to cholinergic, but not GABAergic DBB neurons. Abeta effects on whole cell currents were occluded in the presence of membrane-permeable protein tyrosine kinase inhibitors, genistein and tyrphostin B-44. Our data indicate that the Abeta actions on specific potassium conductances are modulated through a protein tyrosine kinase pathway and that these effects are selective to cholinergic but not GABAergic cells. These observations provide a cellular basis for the selectivity of Abeta neurotoxicity toward cholinergic basal forebrain neurons that are at the epicenter of AD pathology.

Actins↗
PubMed1999

Hypertensive rats exhibit heightened expression of corticotropin-releasing factor in activated central neurons in response to restraint stress.

To test the hypothesis that chronically elevated sympathetic drive is associated with hyperreactiveness of autonomic centers in the brain to stress, adult spontaneously hypertensive rats (SHRs) and two strains of normotensive rats (Wistar Kyoto [WKY] and Sprague Dawley [SD] rats) were acutely exposed to restraint stress; controls from each strain were not stressed. Brain sections were prepared for Fos immunohistochemistry to identify activated neurons in the paraventricular nucleus of the hypothalamus, Barrington's nucleus of the pons, nucleus of the tractus solitarius, and ventrolateral medulla, or for combined Fos immunohistochemistry and corticotropin-releasing factor (CRF) in situ hybridization in the paraventricular nucleus and Barrington's nucleus. Restraint led to increased activation of neurons in all nuclei. Strain differences were found only in the caudal and rostral paraventricular nucleus where restraint resulted in greater numbers of activated neurons in SHRs compared to either normotensive strain. Levels of CRF mRNA in Barrington's nucleus of unrestrained rats were similar among strains. After restraint, mRNA levels and double labeled neurons were increased in Barrington's nucleus of SHRs. In unstressed rats, CRF mRNA levels were elevated in some regions of the paraventricular nucleus in SHRs. After restraint, mRNA levels increased throughout the paraventricular nucleus of SHRs. Significantly greater numbers of double labeled neurons were found in the dorsolateral medial and ventral medial parvocellular paraventricular nucleus of stressed SHRs compared to WKY or SD rats. These data show that chronic elevation in sympathetic activity, present in SHRs, is associated with hyperreactiveness of the paraventricular and Barrington's nucleus including recruitment of neurons to express CRF, and may have important implications for the response of the hypothalamo-pituitary-adrenal axis during stress.

Animals↗
PubMed1999

Effects of restraint stress and spontaneous hypertension on neuropeptide Y neurones in the brainstem and arcuate nucleus.

Neuropeptide Y (NPY) is found in autonomic neurones and participates in regulation of autonomic functions. To investigate the role of NPY in the stress response in normo- and hypertensive rats, activation of brainstem and arcuate nucleus (ARC) NPY neurones and levels of NPY mRNA in the ARC were measured in response to restraint stress in adult spontaneously hypertensive rats (SHRs) and two strains of normotensive rats. Controls from each strain were not restrained. Sections of the brain were prepared for Fos immunohistochemistry and NPY in-situ hybridization to identify activated NPY neurones in the nucleus of the tractus solitarii (NTS), ventrolateral medulla (VLM), and ARC. NPY mRNA levels were quantified in the ARC. In the NTS and VLM of restrained rats, approximately 33% and 75%, respectively, of NPY neurones were activated. No differences among strains were found. In the ARC, about 36% of neurones activated by restraint contained NPY mRNA with no differences found among strains. In unrestrained rats, NPY mRNA levels were significantly elevated in SHRs compared to the normotensive rats. Restraint led to significant decreases in mRNA levels in all strains and mRNA levels among strains were no longer different from one another. These data show that NPY likely participates as a neurotransmitter in the autonomic pathways utilized during stress and originating in the NTS, VLM, and ARC. On the other hand, the decreased gene expression of NPY in the ARC in response to restraint stress argues against a role for activation of autonomic pathways or the hypothalamo-pituitary-adrenal (HPA) axis by NPY from the ARC of stressed rats. The elevated NPY gene expression in resting SHRs compared to normotensive rats is abrogated after restraint, suggesting that this gene is differentially regulated in SHRs compared to normotensive rats.

Animals↗
PubMed1995

Changes in blood volume and pressure induce c-fos expression in brainstem neurons that project to the paraventricular nucleus of the hypothalamus.

Immunohistochemistry for c-fos was combined with retrograde tracing techniques to study the effects of acute reductions in arterial blood pressure due to hemorrhage (HEM) in conscious rats on activated neurons in the brainstem nucleus of the tractus solitarius (NTS) or ventrolateral medulla (VLM) which project to the paraventricular nucleus (PVN) of the hypothalamus. In an attempt to separate blood pressure effects from those associated with changes in blood volume, a similar approach was used to study the effects of drug-evoked hypotension using peripheral infusions of sodium nitroprusside (NP). Few differences were found in patterns or numbers of activated neurons (Fos-immunoreactive) in the NTS or VLM after HEM or NP treatment; only in the NTS at the level of the area postrema were significantly higher numbers of neurons that expressed Fos found in NP rats. In addition, a large proportion of PVN-projecting neurons in the NTS and VLM was activated whereas many activated neurons in the NTS and VLM did not project to the PVN. These results show that a decrease in blood pressure leads to the activation of NTS and VLM neurons but that a change in blood volume does not activate significantly greater numbers of neurons in these areas that project to the PVN or to other targets. Whereas substantial numbers of neurons in the NTS and VLM appear to transmit cardiovascular information to the PVN, many others likely transmit this information to other central targets.

Animals↗
PubMed1995

Hypotension induces Fos immunoreactivity in NADPH-diaphorase positive neurons in the paraventricular and supraoptic hypothalamic nuclei of the rat.

Double staining for Fos and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-D) was used to study the distribution of activated neurons that synthesize nitric oxide in the paraventricular (PVN) and supraoptic nuclei (SON) following hypotensive stimulation in conscious rats. Fos was detected in many magno- and parvocellular NADPH-D positive neurons in response to haemorrhage or drug-evoked hypotension using i.v. infusions of sodium nitroprusside. However, quantitative analysis did not reveal any differences in the number of Fos positive PVN neurons following either mode of stimulation. These results suggest that a subpopulation of hypothalamic NADPH-D positive neurons is activated following hypotensive challenge. This activation of NADPH-D neurons may occur indirectly through other CNS structures that influence the excitability of hypothalamic SON and PVN. Furthermore, the lack of a difference in activated neurons within the PVN following either haemorrhage or nitroprusside infusion suggests that while a drop in blood pressure causes activation of neurons that produce nitric oxide, a decrease in blood volume, which accompanies haemorrhage, does not.

Animals↗
PubMed1980

Residues of nonylphenol in spruce foliage, forest soil, stream water and sediment after its aerial application.

Nonylphenol, a major component of the Matacil (aminocarb) formulation, was mixed with insecticide diluent 585 and applied at 0.47 l/ha by a fixed-wing aircraft to a mixed coniferous forest in Algoma District, Ontario. Residues in white spruce foliage were the highest 1 h after spraying (18.90 ppm) and declined to 60% in the next two hours. After 30 days only 3% of the highest concentration recorded was observed. No detectable levels (less than 0.20 ppm) of nonylphenol were found after 62 days. No residues were detected in any forest soil sample collected after spraying. Nonylphenol residues were about 9 ppb in the stream water 1 h after its application and declined to 50% in the next two hours. Only trace amounts (less than 2.0 ppb) were detected after 5 days and no residues were detected in any water sample taken beyond this time. Residues at trace level (less than 0.10 ppm) were detected in only one sediment sample taken 4 hours after spraying.

Chromatography, High Pressure Liquid↗