Search PubMed⌕ Search

Biomedical subjects

S F Zornetzer

Publications and source records attributed to S F Zornetzer.

At least 19 recordsLinked to original sources
PubMed1985

Noradrenergic changes and memory loss in aged mice.

The present paper addresses the question of whether a decline of central noradrenergic activity is associated with aging and memory loss in mice. Receptor binding techniques were utilized to compare alpha 2-adrenoceptor density in the brains of aged and young mice. Using [3H]rauwolscine, a selective alpha 2-adrenoceptor antagonist, two membrane binding sites were identified which were differentially affected by age. Whereas the density of high-affinity binding sites was unchanged in aged brain as compared to young controls, there was a significant decrease in the number of low-affinity sites. In a separate study, animals were tested for performance on a step-through inhibitory avoidance task, prior to sacrifice and morphological analysis of the brainstem noradrenergic nucleus locus coeruleus (LC). Aged mice exhibited a significant decrease in task retention as compared to young controls; a small, though non-significant, decline was also observed in the numbers of cells within LC. While young mice exhibited low within-group variance, individual aged animals differed greatly in both LC cell number and behavioral performance. Within the aged population, there was a highly significant correlation between the extent of LC cell loss and the degree of memory impairment. These results provide further evidence for an age-related decline in central noradrenergic function which may contribute to an associated memory loss.

Aging↗
PubMed1984

Senescent microstructural changes in rat cerebellum.

Senescent changes in Sprague-Dawley rat cerebellar microstructure have been quantified, focusing on the dominant element of cerebellar information processing, the Purkinje cell. In Golgi-Kopsch sections, many 26-month-old Purkinje cells appear defoliated, with small distal dendrites and spiny branchlets being most affected. The mean Purkinje cell area (soma plus dendrites) in computer-oriented sagittal sections is significantly decreased from 20,675 +/- 1,355 micron2/cell in 6-month-old rats to 17,088 +/- 1,107 micron2/cell in 26-month rats. These morphologic changes may be the hallmark of dying cells: in hematoxylin and eosin (H + E)-stained sections from the same rats we also observe a significant senescent decrease in Purkinje neuron density in every vermis lobule examined (lobules II-VII). Overall, the mean number of Purkinje cells/mm of Purkinje cell layer (measured in 10 micron thick sagittal sections) declines from 16.6 +/- 0.8 cells/mm in young rats to 12.5 +/- 0.2 cells/mm in old rats. As Purkinje cells are lost, so too are ethanolic phosphotungstic acid-stained (EPTA) synapses in the upper molecular layer of the cerebellar vermis (lobules VIII-X), and there is a highly significant within-subjects correlation between Purkinje cell density and synaptic density. Overall, synaptic density (in sagittal, 842 micron2 thin sections) decreases significantly from an average of 150,485 +/- 3,641 synapses/mm2 in 6-month rats to an average of 125,000 +/- 4,849 synapses/mm2 in 26-month rats. These changes are consistent with previous electrophysiologic and biochemical data showing age pathology of the cerebellum.

Aging↗
PubMed1982

Electrophysiological analysis of synaptic distribution in CA1 of rat hippocampus after chronic ethanol exposure.

This study investigated the long-lasting effects of chronic ethanol consumption on the distribution of Schaffer collateral-commissural (SCH/COM) afferents within stratum radiatum of rat hippocampal CA1. Experimental animals were fed an ethanol-containing liquid diet for 20 weeks but were withdrawn from the special diet for at least 8 weeks prior to acute electrophysiological recordings. Field potential laminar analyses were performed by stepping the recording electrode in 25 microns increments through CA1 and sampling evoked potentials at each point. One-dimensional current-source density (CSD) was calculated from the field potential laminar profiles to enhance spatial resolution of current sources and sinks. Stimulation of the SCH/COM afferents elicits short-latency, negative field potentials throughout the synaptic terminal zone (stratum radiatum). CSD analysis in normal animals revealed that the synaptic currents generated in stratum radiatum concentrate into bimodal yet overlapping components, peaking 71.3 microns and 228.3 microns from the pyramidal cell layer. Chronic ethanol treatment produced: (1) a 13.2% shrinkage of the overall extent of current sinks in stratum radiatum; (2) a 37.4% reduction in the spatial extent of the sink proximal to the cell layer; and (3) an increase in the amplitude of the more distal sink. We tentatively propose the proximal and distal sinks to reflect a separation of the COM and SCH afferents, respectively. Chronic ethanol thus appeared to have selectively produced persistent damage to the COM-CA1 pathway.

Action Potentials↗
PubMed1982

Enhanced responsiveness of alpha-noradrenergic receptors following discrete electrolytic lesions of the nucleus locus coeruleus: a behavioral demonstration.

Locomotor activity was evaluated in groups of reserpine-treated mice administered the catecholamine receptor agonists apomorphine and clonidine. Pretreatment of selected groups of mice with discrete electrolytic destruction of the nucleus locus coeruleus (LC) resulted in a clonidine-potentiation of apomorphine-stimulated locomotor activity. This effect was greater in unilateral than bilateral lesioned mice. LC lesions also significantly reduced the level of locomotor habituation achieved within a 60 min observation period. The data are interpreted to suggest that discrete lesions of the nucleus LC results in increased alpha-noradrenergic receptor sensitivity.

Animals↗
PubMed1982

Memory and postsynaptic cholinergic receptors in aging mice.

Significant retention deficits were observed on passive avoidance tasks (step-down and step-through) in 15-, 20-, and 25-month-old male C57BL/6 mice compared with 4- and 8-month-old mice. In contrast, cholinergic muscarinic receptor binding ( [3H]quinuclidinyl benzilate) in cerebral cortex, striatum, hippocampus, and cerebellum in these same animals revealed no difference in this 4- to 25-month age range. In a separate comparison of 4- and 29-month-old female mice, [3H]QNB binding was significantly decreased in the older group in cerebral cortex, hippocampus, and striatum. Environmental enrichment, compared with an impoverished environment, significantly improved retention in mice on 24-hr step-down performance but affected QNB binding only minimally (6-7% decrease of QNB binding in cerebral cortex and hippocampus). Benzodiazepine ( [3H]flunitrazepam) receptor binding was significantly (12-15%) decreased in 29-month-old mice compared with 4-month-old mice in the cerebral cortex, hippocampus, cerebellum, and brain stem.

Aging↗
PubMed1982

Rapid forgetting in aged rats.

The retention performance of young (3-6 months) and aged (24-26 months) Sprague-Dawley rats was evaluated on three separate experimental paradigms. The three paradigms were sequenced so that the first, spontaneous alternation, tested for retention performance of short-term memory; the second, step-down inhibitory (passive) avoidance, tested for long-term memory; while the third, a shock-motivated spatial reversal problem, tested for both short- and long-term memory. The results suggest that aged rats experience significantly more rapid forgetting in both short- and long-term memory systems.

Aging↗
PubMed1981

Augmentation of short-term plasticity in CA1 of rat hippocampus after chronic ethanol treatment.

The neurotoxic effects of chronic ethanol exposure were investigated in rat hippocampus by electrophysiological analysis of the Schaffer collateral-commissural input to stratum radiatum of CA1. Experimental animals were fed an ethanol-containing liquid diet for 20 weeks but were withdrawn from the special diet at least eight weeks prior to acute electrophysiological recordings. Ethanol treatment had no effect on input-output relationships for either the population EPSP or the population spike (PS). During paired-pulse stimulation, the ethanol group exhibited a greater facilitation of the test pulse PS relative to the control group, although potentiation of the EPSP was unchanged. In addition, the ethanol group showed a trend toward greater facilitation of the PS during 5 and 10 Hz tetani. No differences between groups were observed in the magnitude or duration of the long-term potentiation produced by 5, 10 or 100 Hz stimulus trains. Ethanol treatment did significantly reduce the transient spike depression after low frequency stimulation. This pattern of results is similar to that found for treatments which reduce hippocampal recurrent inhibition. Thus, chronic ethanol treatment may produce a lasting disruption of intrinsic inhibitory neurotransmission in the rat hippocampus.

Animals↗
PubMed1981

Senescent pathology of cerebellum: Purkinje neurons and their parallel fiber afferents.

Two groups of naive male Sprague-Dawley rats, 5-7 and 24-26 months of age, were anesthetized with continuous intraperitoneal infusion of 4% chloral hydrate. Stimulation of the cerebellar vermis molecular layer permitted measurements of 12 different electrophysiological properties of parallel fiber Purkinje cell circuitry: parallel fiber conduction velocity, refractory period, threshold, and current dependent volley amplitude; slow negative wave threshold and current dependent amplitude; Purkinje cell activation threshold, latency, and current dependent spike driving; and Purkinje cell inhibitory threshold, latency, and current dependent duration of inhibition. Old subjects demonstrated deficits on all parameters except Purkinje cell inhibitory threshold. The relevance of these findings to our previous research on senescent changes in cell number, lipofuscin deposition, and spontaneous firing of Purkinje cells is discussed.

Afferent Pathways↗
PubMed1980

Neuronal loss in hippocampus induced by prolonged ethanol consumption in rats.

Quantitative neurohistological techniques were used to examine the hippocampal complex of laboratory rats maintained on ethanol-containing or control diets for 5 months followed by a 2-month alcohol-free period. Chronic ethanol consumption resulted in a significant loss of hippocampal pyramidal and dentate gyrus granule cells. This study provides direct evidence that long-term ethanol consumption, in the absence of malnutrition, produces neuronal loss in the central nervous system.

Animals↗
PubMed1978

Ethanol dependence in the rat: role of non-specific and limbic regions in the withdrawal reaction.

Chronic bipolar electrodes were implanted in cortical, limbic, diencephalic and mesencephalic regions of the rat. Following recovery from surgery the rats were maintained for 14--26 days on a liquid diet in which 35--42% of total calories were provided by ethanol. Following ethanol withdrawal, electrographic and behavioral monitoring was continued for 8--10 h. The withdrawal of ethanol resulted in the time-dependent appearance of a variety of withdrawal signs including tail arching, ataxia, rigidity, tremor and spontaneous and audiogenic convulsions. These behavioral signs were accompanied by the development of epileptiform abnormalities across wide-spread brain regions. Analysis of preconvulsive spike activity revealed a greater spike frequency in limbic, mesencephalic and non-specific diencephalic regions, as compared to those in cortex and specific diencephalon. Seizure discharge during the tonic-clonic phase of the primary audiogenic convulsion was initiated in the mesencephalon or amygdala, but spread rather extensively to the remainder of the brain. In those instances, however, where multiple convulsions occurred following the audiogenic convulsions, there was a marked decline in spread of seizure discharge to the cortex. These results were interpreted to support the notion that some degree of neuroanatomical specificity exists in the genesis of epileptiform abnormalities during ethanol withdrawal. A comparison of these results with those studying the neural mechanisms underlying other forms of generalized epilepsy was made. It is hypothesized that central pacemaking regions such as medial thalamus or reticular formation may serve to organize isolated epileptiform activity into coherent patterns of paroxysmal activity throughout the brain during the ethanol withdrawal syndrome.

Alcoholism↗