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Biomedical subjects

B A Pappas

Publications and source records attributed to B A Pappas.

At least 73 records · Page 4Linked to original sources

Are the dorsal noradrenergic bundle projections from the locus coeruleus important for neocortical or hippocampal activation?

Three different methods were used to examine the importance of the dorsal noradrenergic bundle projections from the locus coeruleus (LC) in activation of the neocortex and hippocampus in freely moving rats. (1) After cerebral norepinephrine (NE) was depleted by systemic neonatal injections of 6-hydroxydopamine (6-OHDA) both atropine-resistant and atropine-sensitive forms of hippocampal rhythmical slow activity (RSA; theta) and neocortical low voltage fast activity (LVFA) remained intact. Compared to controls the adult rats treated with 6-OHDA in infancy reared less in a 24 h time sample of behavior and ran less in running wheels. (2) Brain dopamine and NE were also depleted by systemic injections of alpha-methyl-p-tyrosine. Following this treatment rats were very inactive behaviorally. However, normal activation of the hippocampus and neocortex was still present. (3) In normal rats, electrical stimulation of the LC was relatively ineffective, compared to stimulation of nucleus reticularis pontis caudalis, in producing behavioral changes (especially locomotion) or either atropine-resistant or atropine-sensitive hippocampal RSA or neocortical LVFA. It is concluded that the locus coeruleus is not important for cerebral activation, and that mechanisms for cerebral activation are probably diffusely represented in the reticular core. The data also show that when attempting to assess the effect of experimental manipulations on brain activity it is essential to control for the possible effects of changes in behavior.

Animals↗

Cardiac cycle phase and movement and reaction times.

The EKG was recorded while Ss differentially responded to auditory or visual stimuli in a reaction time task. The EKG record was analyzed by dividing each R-R interval encompassing a stimulus presentation into 9 equal phases. Reaction times were determined as a function of the phase encompassing stimulus onset while movement times were determined for the phase in which the response was initiated. Only reaction time significantly varied with cardiac cycle, with reactions during the second phase being slower than later phases.

Acoustic Stimulation↗

Neonatal locomotor and long-term behavioral effects of d-amphetamine in the rat.

Locomotor activity in the neonatal rat was found to increase from birth until the beginning of the 3rd week of life, at which time it peaked and then subsequently declined. Subcutaneous injections of both .25 and 2.0 mg/kg of d-amphetamine increased activity in rats 1-21 days of age, with the maximum effect observed at 4 days of age. No tolerance to d-amphetamine was observed after 6 daily injections beginning at 1, 7, or 14 days of age. The decline in the excitatory effects of the drug thus reflected maturational changes in response to it. Consistent with other observations from this laboratory, no persisting effects of the neonatal drug treatment was observed on adult 2-way avoidance learning.

Age Factors↗

Early behavioral and catecholaminergic effects of 6-hydroxydopamine and guanethidine in the neonatal rat.

New born rats received 7 consecutive daily injections of 6-hydroxydopamine (6-OHDA) or guanethidine. Locomotor activity, measured at 3 day intervals, was differentially affected by these drugs, although neither drug elimination a characteristic pattern of ontogeny of locomotor activity. Differing neurochemical effects were also observed. 6-OHDA decreased tyrosine hydroxylase activity in cortex and cerebellum, increased it in the brainstem and had no effect on the hypothalamus. Guanethidine slightly elevated enzyme levels in all four brain regions, with the elevation in brainstem significant at 16 days of age. Regional brain changes in enzyme activity after 4 daily 6-OHDA injections beginning at 1, 5 or 9 days of age indicated that toxic effect of 6-OHDA upon catecholaminergic neurons was age dependent. These data are not consistent with a simple interpretation either in terms of maturational changes in blood brain barrier permeability to 6-OHDA or neuronal uptake of the drug. Further analyses of brainstem areas indicated that the increased brainstem enzyme activity after 6-OHDA was restricted to the pons.

Aging↗

Prenatal exposure to antiadrenergic antihypertensive drugs: effects on neurobehavioral development and the behavioral consequences of enriched rearing.

One of the beta blockers propranolol (5 or 20 mg/kg) or atenolol (5 or 20 mg/kg) or the alpha-2 agonist clonidine (20 or 100 micrograms/kg) was administered in the drinking water to pregnant Wistar rats over gestation days 1 to 21. Maternal weight gain, litter size or litter weight were unaffected as were a number of measures of physical and behavioral development. The rats were raised after weaning in either enriched or impoverished housing. At maturity, male but not female rats that had been prenatally exposed to either of the three drugs weighed less than the controls. Testing for cognitive function using an automated version of the Hebb-Williams maze indicated impaired spatial maze problem solving ability for female rats that had been exposed to propranolol (20 mg/kg) and raised in impoverishment. Generally, enriched-reared rats committed fewer errors on the maze problems. Prenatal exposure to the drugs did not alter the beneficial effects of enriched rearing on maze solving. However, clonidine-exposed (100 micrograms/kg) female rats that were raised in enrichment showed a significantly increased mortality rate. Thus, prenatal exposure to all of these drugs exerted effects which were latent, appearing in adulthood, and which were to some extent precipitated by environmental factors. We conclude that these drugs may be physical and behavioral teratogens for the rat.

Animals↗

Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients.

Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients. Item scores from the Mattis Dementia Rating Scale (MDRS) and the Mini-Mental State Examination (MMSE) from 389 patients with probable Alzheimer's disease were submitted to principal component analysis with orthogonal rotation. The optimal solution identified four factors that reflected the cognitive domains of attention/registration, verbal fluency/reasoning, graphomotor/praxis and recent memory. A subgroup of patients was identified for whom both the MDRS and the MMSE had been administered within the 12 months before death. Scores were assigned to these patients for the four factors. These cognitive-domain scores were then correlated with postmortem choline acetyltransferase (ChAT) activity in the medial frontal cortex, inferior parietal cortex, and hippocampus. ChAT activity in both the medial frontal and the inferior parietal cortex significantly correlated with scores on the graphomotor/praxis factor. Medial frontal ChAT also correlated significantly with the attention/registration scores. Hippocampal ChAT correlated significantly only with recent memory scores. These results are consistent with current animal research regarding the effect of selective cholinergic lesions on behavior.

Aged↗

Cleavage of amyloid precursor protein elicited by chronic cerebral hypoperfusion.

In the present study, we sought to determine whether low-grade, chronic vascular insufficiency induced in a rodent model of chronic cerebrohypoperfusion is sufficient, in and of itself, to trigger cleavage of the amyloid precursor protein (APP) into beta A-sized fragments. We report that chronic two vessel occlusion (2VO) results in progressive accumulation of beta A peptides detected by Western analysis in aged rats correlating with a shift in the immunohistochemical localization of APP from neurons to extracellular deposits in brain parenchyma. These data indicate that the 2VO paradigm reproduces features of beta A biogenesis characteristic of sporadic Alzheimer's disease.

Amino Acid Sequence↗