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Biomedical subjects

T L Petit

Publications and source records attributed to T L Petit.

At least 37 records · Page 2Linked to original sources
PubMed1988

The neurobiology of learning and memory: elucidation of the mechanisms of cognitive dysfunction.

This paper reviews evidence which suggests that there is a series of events at the synaptic level, beginning with synaptic activation, responsible for the formation of memories. Synaptic use above routine levels activates NMDA receptors which allows calcium influx into the neuron. Calcium appears to trigger changes in synapse and synaptic terminal shape (via cytoskeletal activation), and an increase in synaptic size (via new protein synthesis). New synapses ultimately form either de novo or by splitting, and new dendritic spines and dendritic length is added. Several forms of cognitive dysfunction, such as Downs syndrome, aging and Alzheimer's disease, and exposure to the neurotoxins lead or aluminum appear to involve, at least in part, disruptions in this process. Evidence is reviewed to support the theory that memories may involve alterations in specific sets of synapses located at specific dendritic locations; this theory may explain some of the learning and memory deficits seen in conditions resulting in cognitive dysfunction.

Cognition Disorders↗
PubMed1987

Neocortical synaptogenesis, aging, and behavior: lifespan development in the motor-sensory system of the rat.

Little evidence presently exists on the development and aging of synaptic contacts and their relationship to behavior, particularly in nonvisual brain areas. To investigate this interrelationship, rats at a series of developmental ages [postnatal day 1 (P1) to P90] were initially examined on a battery of motor tasks. The battery, ranging from simple reflexive tests to tests of complex locomotor capacities, consisted of tactile-induced forelimb placing, chin-induced placing, body righting, climbing an inclined plane, traversing a narrow beam, and keeping up with a revolving wheel. Following completion of the behavioral testing, the animals, together with an additional group of aged (28- to 29-month-old) rats, were killed and their motor-sensory cortex was removed, stained with osmium tetroxide or ethanol phosphotungstic acid (EPTA), and examined under electron microscopy for density of synaptic contacts. Simple motor abilities such as tactile-induced placing was present by the end of the first postnatal week, with locomotor performance reaching a mature level by the end of the third postnatal week, and intermediate task abilities maturing within this range. Paralleling the development of complex locomotor skills was a sharp increase in synaptic density in the molecular layer of the motor-sensory cortex, commencing in the second postnatal week and peaking at P30. After P30 there was a sharp decline in synaptic density as well as a decline in performance on some motor tasks, although these two functions seemed to be occurring independently. There was a continued, but less dramatic synaptic loss evident in the aged rats.

Aging↗
PubMed1987

Synaptic structural changes during development and aging.

Although a great deal is known about the development of synaptic number, comparatively little is known about the effects of development, and particularly aging, on the structure of the synapse. The present study examined synaptic structure in the molecular layer of the motor-sensory neocortex during early development (postnatal days (P) 1, 3, 5, 7, 10, 15, 20, 30), adulthood (P60, 90), and old age (28 months). Tissue was stained with osmium tetroxide (osmium) or ethanol phosphotungstic acid and the following synaptic characteristics were quantified: (1) presynaptic element length, area, thickness, maximal projection height and smoothness, and number and size of vesicles adjacent to the presynaptic element; (2) postsynaptic element length, area, and thickness; and (3) cleft width. There is an early developmental increase in synaptic element length, followed by an increase in thickness into adulthood. During development the height and width of the presynaptic dense projections increase, after which they remain stable. While the number of adjacent synaptic vesicles increases throughout the lifespan, there is a parallel decrease in their size. During the period of rapid synaptogenesis in this brain region there are no decreases in any of the synaptic structural parameters examined, indicating that newly generated synapses are either formed the same size as the existing mature synapses, or are extremely plastic and grow very rapidly. Unlike age-associated changes in synaptic number, no changes were found in synaptic structure during aging.

Aging↗
PubMed1986

Zinc deficiency in the postnatal rat: implications for lead toxicity.

Zinc (Zn), an essential element in the diet of mammals, appears to have a high affinity for the hippocampus during development, particularly the mossy fiber pathway (MFP). Lead (Pb) competes at several physiological levels with Zn, and is also selectively sequestered in the MFP. It has been suggested that Pb might exert its neurotoxic effects by displacing Zn and disrupting its functioning in the hippocampus. This study was conducted to address this possibility by examining hippocampal structure and function in perinatally Zn-deprived animals, and comparing the results with those previously observed under identical conditions in Pb-exposed rats. From postnatal day 1 (P1) to P25, Long-Evans hooded rat pups and their mothers were placed on a Zn deficient or control diet. On P25, weight-matched pairs of animals were selected for morphometric evaluation of the MFP following Timm's silver sulfide staining; no differences between groups were observed. Animals were tested at maturity in three behavioral tasks considered sensitive to hippocampal dysfunction. Zn deficiency produced no significant alterations in open field activity levels or passive avoidance performance; however, it did induce significantly reduced rates of spontaneous alternation. These results indicate few neurobehavioral similarities between Pb exposed and Zn deficient animals.

Animals↗
PubMed1986

Differential survival of fetal and adult neurons and non-neuronal cells exposed chronically to ethanol in cell culture.

Neural cell cultures of dissociated dorsal root ganglia (DRG) were used to investigate the effect of chronic ethanol exposure on the differential survival of fetal and adult neurons and non-neuronal cells. After 12 days of culture in ethanol (20 DIV), counts were made of both neurons and non-neural cells. Unexpectedly, the adult neurons showed a slightly greater degeneration with increasing ethanol than fetal neurons; the adult and the fetal neurons had LD50s of 1.78 and 2.08 gm% respectively. In contrast, for the non-neuronal cells the differential response was reversed; the fetal non neuronal cells were more affected than the adult non neuronal cells with LD50s of 0.7 gm% and 0.94 gm% for fetal and adult non-neuronal cells respectively. Also independent of developmental stage, the non-neuronal cells were 2 to 3 times more sensitive (in terms of survival) to increasing ethanol than the neurons. Electron microscopic examination suggested an increased amount of lipofuscin and dilated endoplasmic reticulum in the adult neurons exposed to ethanol. The possible significance of the results to fetal alcohol syndrome (FAS) is discussed.

Age Factors↗
PubMed1986

The effects of lead exposure on field potentials of CA3 pyramidal cells from mossy fiber stimulation in rat hippocampus.

Previous anatomical evidence indicates that lead (Pb) alters development of the hippocampus and electrophysiological data suggest that Pb interferes with several neuronal systems outside the hippocampus. The present research was undertaken to examine the possibility that exposure to Pb early in development induces electrophysiological alterations in field potentials of CA3 pyramidal cells. Rat pups were exposed to Pb for the first 25 days of age via maternal milk. During this period, dams were fed diets containing either 4% PbCO3 or a Na2CO3 control diet. At 39-54 days of age, 15 sec trains of 20 Hz electrical stimuli at near-maximal intensities were delivered to the dentate granule cells of anaesthetized rats. No significant differences between Pb-treated and control animals were detected for the evoked responses during or after the stimulus trains. However, spreading depression was observed in a greater proportion of Pb-treated animals and more frequently within single Pb-treated animals than in controls. Repetitive bursting, which followed termination of most 20-Hz trains, was significantly longer for Pb-treated animals. The duration of single bursts and the interval between bursts in a given episode were also longer in Pb-treated animals. These data support the hypothesis that developmental Pb exposure alters the electrophysiological properties of CA3 pyramidal cells.

Animals↗
PubMed1985

Neurobehavioral development following aluminum administration in infant rabbits.

Aluminum (Al) is known to be a neurotoxic agent in some species, inducing neurofibrillary tangles, dendritic atrophy, and behavioral deterioration, and has been implicated as a possible agent in human Alzheimer's disease and dialysis dementia. This study was conducted to assess the neurotoxic effects of Al in infant rabbits, and to compare the effects to those previously observed to follow exposure in the adult animal. Aluminum tartrate (2 microM) or physiologic saline was injected into the right lateral ventricle of 2-day-old (day P3) New Zealand white rabbits. The animals were trained in a step-down active avoidance task on P12 and retested 1 day later. They were killed on P20, and their hippocampal CA1 pyramidal cells examined for neurofibrillary tangles or prepared with the rapid Golgi stain for an examination of dendritic development. Additional animals were similarly infused with 1 or 3 microM Al for qualitative and some quantitative observations. No overt neurologic signs were observed in the 1- or 2-microM groups, however, most of the 3-microM group died between P10 and P20. Although there were no significant differences between the 2-microM and control animals on either learning or retention of the active avoidance task, deficits in retention of the task were observed in the 3-microM group. Neurofibrillary tangles in CA1 pyramidal cells were observed with dosages of 1 microM and higher. In the 2-microM group, the pattern of dendritic arborization in CA1 pyramidal cells was consistent with that expected for cells retarded in their development. These results have implications in terms of developmental differences in the neurobehavioral effects of Al.

Aluminum↗
PubMed1985

Establishment of status epilepticus by limbic system stimulation in previously unstimulated rats.

A syndrome of convulsive status epilepticus developed in 4 of 18 rats which had been treated with continuous sine wave stimulation incrementally raised to 40 microA through limbic system electrodes. The syndrome was characterized by recurrent behavioral seizures, continuous EEG spiking, and marked neuropathology. In three other animals, the stimulation treatment produced a syndrome of nonconvulsive status epilepticus manifested by an electrophysiologic record of continuous seizure activity, without accompanying tonic-clonic movements. The poststimulatory effect was correlated with the animals' response to the stimulation, and was independent of whether the electrode was positioned in the hippocampus or amygdala. If an animal developed repeated convulsive seizures during the stimulation, such seizures were likely to persist after the stimulation offset. These results indicate that persistent limbic system activation can produce a syndrome of recurrent seizures similar to that caused by either neurotoxic drugs or by limbic system activation in kindled rats.

Amygdala↗
PubMed1985

Postnatal lead exposure and the cholinergic system.

Previous reports have suggested that the behavioral effects of early lead (Pb) exposure may be due to an underlying deficiency in cholinergic function. To further examine this possibility, Long-Evans hooded rat pups were exposed to Pb for the first 25 postnatal days via the maternal milk. Dams were fed either 4.0% PbCO3 (High Pb), 0.4% PbCO3 (low Pb) or a Na2CO3 control diet throughout this period. Beginning at 65 days of age, animals were tested on behavioral tasks sensitive to both Pb exposure and cholinergic deficiency. Exposure to both levels of Pb impaired passive avoidance acquisition and produced lower rates of spontaneous alternation. Pb, however, had no clear effects on open field activity. The cholinergic agonist physostigmine (0.05 and 0.075 mg/kg) did not affect the behavior of control animals on any task, but in both Pb exposed groups physostigmine improved passive avoidance acquisition, increased the rate of spontaneous alternation and lowered open field activity scores. The cholinergic antagonist scopolamine (0.4 mg/kg) impaired passive avoidance acquisition, lowered the rate of spontaneous alternation and increased open field activity scores in control animals. Consistent with behavior characteristic of an inverted U shaped response curve, scopolamine (0.2 and 0.4 mg/kg) improved passive avoidance acquisition in both Pb exposed groups and decreased open field activity scores in the High Pb group. In all cases, the behavioral response of the Pb exposed animals may be interpreted as responses characteristic of cholinergically deficient animals. These results thus provide further evidence for cholinergic system involvement in the behavioral changes observed following early exposure to Pb.

Animals↗
PubMed1984

Synaptic development in the human fetus: a morphometric analysis of normal and Down's syndrome neocortex.

Postmortem tissue was obtained from six normal and four Down's syndrome brains ranging in age from 12 to 40 weeks postconception. Tissue was processed for electron microscopy using routine osmium and EPTA staining procedures, and to examine synaptic development, photomicrographs were systematically taken throughout the molecular layer of the sensorimotor neocortex. The number of EPTA-stained synapses were consistently greater than the number of osmium-stained synaptic contacts. A progressive increase in synaptic density throughout the range of ages examined was observed for both normal and Down's syndrome tissue. There was also an increase with developmental age in apparent measures of synaptic maturity, e.g., an increased ratio of mature to primitive contacts and asymmetrical to symmetrical contacts. In normal tissue, pre- and postsynaptic membrane lengths were observed to increase with the ages studied, whereas synaptic membrane widths appeared to attain mature values by 29 weeks postconception. Cleft width remained fairly constant to 28 weeks postconception. Although direct statistical comparisons could not be made, in Down's tissue synaptic parameter development was generally less consistent and the parameters appeared to be reduced during the later stages of development studied.

Down Syndrome↗
PubMed1983

Development and plasticity of the hippocampal-cholinergic system in normal and early lead exposed rats.

A review of previous evidence suggested the possibility of a functional association between the effects of early lead (Pb) exposure, hippocampal damage and cholinergic deficiency. To further assess this possibility, Long-Evans hooded rat pups were exposed to Pb for the first 25 postnatal days via the maternal milk. Dams were fed either 4.0% PbCO3 or a Na2CO3 control diet throughout this period. At 30 and 115 days of age, the brains of Pb and control animals were processed for acetylcholinesterase histochemistry. Morphometric evaluation of the molecular layer of the hippocampal dentate gyrus indicated that while absolute increases in the dimensions of the afferent systems to the hippocampal dentate gyrus are observed between 30 and 115 days of age, no significant rearrangement in the pattern of lamination occurs during this time. No effects of Pb were seen on the development of the cholinergic innervation of this brain region at either of these ages. Unilateral perforant path transections performed on Pb and control animals at 100 days of age indicated reduced cholinergic plasticity in the molecular layer of the hippocampal dentate gyrus of Pb exposed animals, as indicated by AChE histochemistry. These findings indicate that a decrease in neuroanatomical plasticity may be a critical brain mechanism underlying the learning deficits observed following exposure to Pb.

Acetylcholinesterase↗
PubMed1983

Early lead exposure and the hippocampus: a review and recent advances.

A review of previous evidence suggests an association between early Pb exposure and hippocampal dysfunction. This report summarizes recent experiments conducted in both our laboratory and others' examining the effects of early Pb exposure on hippocampal morphological development, and behaviors characteristic of hippocampal dysfunction. Following postnatal Pb exposure marked reductions are seen in general hippocampal development and in the axonal and dendritic development of hippocampal dentate granule cells. Correlated with these neuroanatomical changes are Pb induced behavioral changes which show numerous similarities to those behavioral changes seen following damage to both the adult and developing hippocampus. These observations thus support the suggestion that the hippocampus may play a critical role in mediating many of the behavioral changes observed following early Pb exposure, as well as indicate that the hippocampus may serve as an excellent model system for further examining the neurobehavioral effects of Pb. However, as other brain areas are also clearly effected by Pb, alternative explanations for these lead induced behavioral changes are also discussed.

Acoustic Stimulation↗
PubMed1981

Abnormal electric membrane properties of Down's syndrome DRG neurons in cell culture.

Cell cultures were prepared from normal and Down's syndrome dorsal root ganglia (DRG). Both pre- and postnatal specimens were utilized; 8 normal and 4 Down's. Cultures were maintained in medium with normal (4 mM) and elevated (20 mM) potassium (K) since the latter was found to enhance neuron survival. After various period of incubation, cultures were transferred to normal K medium and their electrical membrane properties (EMP) determined using intracellular recording techniques. An analysis of variance was performed with 5 covariates: developmental stage, culture duration, K concentration, type of action potential, and neuronal surface area. This analysis indicated that the Down's neurons had abnormal EMP, the most affected being the after hyperpolarization (-41%), membrane time constant (+30%), threshold rheobasic depolarization (-22%), rate of falling phase of action potential (-20%), specific membrane resistance (+18%) and absolute refractory period (+12%). All differences were also observed when samples of normal and Down's neurons were matched for the 5 covariates mentioned above, take separately. If the abnormal EMP observed in the present study for Down's DRG neurons in culture occurred for CNS neurons in situ they would disrupt the normal function of the nervous system and could therefore constitute the neurobiological basis of the mental retardation observed in Down's syndrome.

Action Potentials↗