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E Head

Publications and source records attributed to E Head.

At least 37 records · Page 2Linked to original sources
PubMed2000

Ultrastructural analyses of beta-amyloid in the aged dog brain: neuronal beta-amyloid is localized to the plasma membrane.

1. An electron microscopic study was undertaken to study beta-amyloid (Abeta) deposition and neuropathology in aged dogs. 2. A positive correlation between Abeta deposits and neuropathology was found in some dogs. Massive Abeta deposition was correlated to advanced lesions. 3. By use of immunocytochemistry Abeta fibers were identified within plaques, around vessels and in association with cell membranes.

Aging↗
PubMed2000

Ultrastructural evidence of fibrillar beta-amyloid associated with neuronal membranes in behaviorally characterized aged dog brains.

The aged dog brain accumulates beta-amyloid in the form of diffuse senile plaques, which provides a potentially useful in vivo model system for studying the events surrounding the deposition of beta-amyloid. We used postembedding immunocytochemistry at the electron microscopic level to determine the subcellular distribution of beta-amyloid 1-40 and beta-amyloid 1-42 peptides in the prefrontal and parietal cortex of behaviorally characterized dogs ranging in age from one to 17 years. Immunogold particles signaling beta-amyloid 1-42 occurred over intracellular and extracellular fibrils that were approximately 8 nm in width. Intracellular beta-amyloid 1-42 fibrils were found in close proximity to glial fibrillary acidic protein fibers within astrocytes, but only in cells with signs of plasma membrane disruption. Neuronal labeling of beta-amyloid 1-42 appears to be associated with the plasma membrane. Membrane-bound beta-amyloid 1-42 occurs in the form of fine fibrils that are embedded in the dendritic membrane and appear to project into the extracellular space as determined by quantitative analysis of the immunogold particle distribution. Bundles of beta-amyloid 1-42 were also closely associated and/or integrated with degenerating myelin sheaths of axons. In one dog that was impaired on several cognitive tasks, extensive beta-amyloid 1-42 deposition was associated with microvacuolar changes and vascular pathology. The present findings suggest that beta-amyloid 1-42 may be generated at the dendritic plasma membrane as well as in intracellular compartments. The close association between beta-amyloid 1-42 and destroyed myelin suggests one possible new mechanism by which beta-amyloid 1-42 induces neurodegeneration.

Amyloid beta-Peptides↗
PubMed1999

Clinical and pathological evidence for a frontal variant of Alzheimer disease.

OBJECTIVE: To evaluate the clinical and pathological features of a subgroup of patients with Alzheimer disease (AD) who exhibited early and disproportionately severe impairments on tests of frontal lobe functioning. We hypothesized that these patients would exhibit a greater degree of either neurofibrillary tangle (NFT) or senile plaque pathology in the frontal lobes than would patients with typical AD. DESIGN AND OUTCOME MEASURES: We examined the neuropsychological profiles and senile plaque and NFT accumulation in the frontal, entorhinal, temporal, and parietal cortices in 3 patients with AD who exhibited disproportionate frontal impairments during early stages of dementia (frontal AD) and 3 matched patients with typical AD (typical AD). RESULTS: Compared with the typical AD group, the frontal AD group performed significantly worse on 2 tests of frontal lobe functioning and on the Wechsler Adult Intelligence Scale-Revised Block Design test. No significant group differences were found on other tests. Analysis of brain tissue samples demonstrated that, despite comparable entorhinal, temporal, and parietal NFT loads, the frontal AD group showed a significantly higher NFT load in the frontal cortex than the typical AD group. Senile plaque pathology in the frontal and entorhinal cortices did not differentiate the 2 groups. CONCLUSIONS: We identified a subgroup of patients with pathologically confirmed AD who presented in the early stages of dementia with disproportionate impairments on tests of frontal lobe functioning and had a greater-than-expected degree of NFT pathology in the frontal lobes, suggesting the existence of a frontal variant of AD that has distinctive clinical and pathological features.

Aged↗
PubMed1999

The presence of isoaspartic acid in beta-amyloid plaques indicates plaque age.

Extracellular deposits of fibrillar beta-amyloid are a characteristic neuropathology of Alzheimer's disease (AD). We have developed a novel antibody to a hypothesized "older isomer" of the amyloid protein. This antibody, raised against a synthetic beta-amyloid peptide containing isoaspartic acid at position 7 (isoaspartic-7-Abeta), reacts with isoaspartic-7-Abeta, a nonenzymatic modification found in long-lived proteins. Plaques stained with this antibody are thioflavine positive and are found throughout the frontal and entorhinal cortices of AD cases. In frontal cortex, isoaspartic-7-Abeta plaques are clustered but have a widespread distribution in all cortical layers. Isoaspartic-7-Abeta is found primarily in the core of individual plaques surrounded by nonisomerized amyloid. Activated microglia are associated with plaques containing isomerized and nonisomerized amyloid. In contrast to AD, isoaspartic-7-Abeta plaques in Down's syndrome (DS) cases are found primarily in the superficial layers of frontal cortex. Using image analysis isoaspartic-7-Abeta deposition was correlated with dementia severity in AD and with age in DS. The results indicate that this antibody against altered aspartyl amyloid could be a useful indicator of the age of amyloid plaques.

Adult↗
PubMed1998

Selective loss of early suppression in the dentate gyrus precedes kainic acid induced electrographic seizures.

The role of inhibitory and facilitatory processes in the induction of seizures was studied in a kainic acid (KA) model of epilepsy. The dentate gyrus (DG) response to paired-pulse stimulation of the perforant path (PP) was monitored prior to and immediately following the initial KA induced afterdischarge (AD) in rats chronically prepared with stimulation recording electrodes. The subjects received a 1-h program of stimulation consisting of repeated sequences of pulse pairs at a short (20-30 ms), intermediate (45-90 ms), and long (200-300 ms) interpulse interval (IPIs). The stimulation program was administered both under control conditions and immediately following systemic injection of KA. During the control condition, stable suppression of population spike measures was obtained at the short (early phase) and long (late phase) IPIs, while facilitation was observed at the intermediate IPI. Administration of KA resulted in a progressive loss of suppression prior to the initial AD at the short IPI; neither facilitation nor the late phase of suppression were significantly affected. The early phase decreased further following the initial discharge. Since the early phase most likely reflects recurrent inhibition, these results provide evidence that inhibitory loss precedes the occurrence of KA induced AD, and that this inhibitory loss is increased further following the initial evoked AD. A use-dependent disinhibition is one possible explanation for the change in responsiveness that precedes the AD. This disinhibition could result from a depressed response at GABA-A receptors, an increased responsiveness at GABA-B receptors or possibly both.

Animals↗
PubMed1997

The progression of beta-amyloid deposition in the frontal cortex of the aged canine.

Brains from 41 aged canines (> or = 10 years of age) were examined immunohistochemically to characterize the laminar distribution and age-related progression of beta-amyloid (A beta) in frontal cortex. We classified the A beta patterns into four distinct types. Type I was characterized by small, faint deposits of A beta in deep cortical layers. Type II consisted of diffuse deposits of A beta mainly in layers V and VI. Type III had both dense plaques in superficial layers, and diffuse deposits in deep layers. Finally, Type IV had solely dense plaques throughout all layers of cortex. We compared the A beta distribution pattern between the Old canines (10-15 years, n = 22) and the Very Old canines (> 15 years, n = 19). The Old group primarily had negative staining, or Type I and Type II patterns of amyloid deposition (73%). Conversely, the Very Old group had predominantly Types II, III and IV deposits (89.5%), a difference that was significant (P < 0.05). We suggest that A beta deposition in canine frontal cortex is a progressive age-related process beginning with diffuse deposits in the deep cortical layers followed by the development of deposits in outer layers. In support of this hypothesis, the deeper layer diffuse plaques in the Very Old group of dogs also contain the largest proportion of beta-amyloid with an isomerized aspartic acid residue at position 7, indicating that these deposits had been present for some time. We also observed fiber-like A beta immunoreactivity within regions of diffuse A beta deposits. These fibers appeared to be degenerating neurites, which were negative for hyperphosphorylated tau. Therefore, these fibers may represent a very early form of neuritic change that precede tau hyperphosphorylation or develop by an alternative pathway.

Aging↗
PubMed1997

Open field activity and human interaction as a function of age and breed in dogs.

Open field (OF) activity was studied in kennel reared purebred beagles from two separate colonies (2-13 years in age) and pound source mixed breed dogs (9 months to 10 years in age). Dogs were observed for 10 min sessions and records were taken of: locomotion, urination, sniffing, grooming, rearing, vocalizing, jumping frequencies and inactivity (16). Since dogs are uniquely social towards people, we also measured human interaction (HI), which recorded the same behaviors as during OF when a person was present in the room. Measures of exploratory behavior decreased as a function of age in pound source dogs in the OF test, but not in beagles from either colony. No breed differences were found between the young dogs. In the HI test, age effects were found in beagles but not pound source dogs. OF activity correlated with tests of cognitive function, but differences were found between the three groups. These findings indicate that OF activity is age-sensitive in dogs, but that breed and test conditions are also essential factors.

Aging↗
PubMed1997

Effects of extended electrical kindling on exploratory behavior and spatial learning.

Short-term electrical kindling, a widely used experimental model of epilepsy, appears to have little effect on behavior. The effects of extended kindling are largely unknown. Rats implanted with kindling electrodes in amygdala (AM) or perforant path (PP) received 300 kindling trials over approximately 7 months, and were tested in the Morris watermaze after a 7-10 day recovery period. Kindled animals were impaired during the initial training on hidden-platform acquisition, but not in retention of platform location. No deficits were found in acquiring a new hidden-platform location, latency to reach a visible-platform, or in swim speed. Open-field activity showed a sustained increase when tested during kindling, but only a transient increase when tested following suspension of kindling. Similar results were obtained for both AM and PP kindled animals. Hence, long-term kindling of both of these sites produced behavioral changes that were transient in nature. Further, these results also indicate that propagation of seizure activity from remote sites can alter hippocampally-mediated or related behavior.

Animals↗
PubMed1996

Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine.

It is well known that beta-amyloid accumulates abnormally in Alzheimer's disease; however, beta-amyloid's relationship to cognitive dysfunction has not been clearly established and is often confounded by the presence of neurofibrillary tangles. We used canines to investigate the relationship between beta-amyloid accumulation and cognitive function in an animal model of aging lacking neurofibrillary tangles. The performance of 20 canines (11 purebred beagles and 9 mongrels) on a battery of six cognitive tasks was measured. These tasks included Reward Approach and Object Approach learning, as well as Discrimination, Reversal, Object Recognition, and Spatial learning and memory. Aged canines were impaired on some tasks but not others. beta-Amyloid-immunopositive plaques were found in many of the older animals. Plaques were all of the diffuse subtype and many contained intact neurons detected with double-labeling for neurofilaments. No neurofibrillary tangles were detected. beta-Amyloid was also associated with the processes of many neurons and with blood vessels. Using computerized image analysis, we quantified the area occupied by beta-amyloid in entorhinal cortex, frontal cortex, and cerebellum. Controlling for age-related increases in beta-amyloid, we observed that increased beta-amyloid deposition is strongly associated with deficits on Discrimination learning (r = .80), Reversal learning (r = .65), and Spatial learning (r = .54) but not the other tasks. There were a few differences between breeds which are discussed in the text. Overall, these data suggest that beta-amyloid deposition may be a contributing factor to age-related cognitive dysfunction prior to the onset of neurofibrillary tangle formation.

Alzheimer Disease↗
PubMed1996

The effects of L-deprenyl on spatial short term memory in young and aged dogs.

1. Young and aged dogs were tested on a spatial memory task using a delayed non matching to sample technique. Dogs were tested with 20, 70 and 110 second delay intervals. Animals were pretrained to a stable level of performance prior to treatment. 2. During treatment periods, dogs were orally administered a placebo or I-deprenyl in doses of 0.5 and 1.0 mg/kg in a repeated measures design. 3. Young dogs did not show any significant effects of I-deprenyl, however the sample size was limited. 4. L-deprenyl administration improved spatial memory in aged dogs. 5. The optimal dose or length of treatment time of I-deprenyl varied among individual dogs.

Aging↗
PubMed1995

Development of spontaneous seizures over extended electrical kindling. II. Persistence of dentate inhibitory suppression.

The effect of an extended program of perforant path or amygdala kindling on paired-pulse suppression in the dentate gyrus was studied in male hooded rats. Repeated kindling stimulations were delivered twice or three times daily until either 300 stimuli had been delivered or generalized convulsions had been observed to occur spontaneously. Paired-pulse suppression was monitored prior to and over the course of kindling using a standard variable interval paradigm. We also used a variable intensity paradigm in which the intensity of the conditioning pulse was varied while the test pulse intensity was fixed at 600 microA and the interpulse interval was fixed at 30 ms. Both procedures revealed progressive increases in paired-pulse suppression which persisted over the course of kindling. This increased inhibition also persisted in animals which developed spontaneous seizures. The variable intensity paired-pulse procedure also allowed us to monitor facilitation effects which were relatively uncontaminated by recurrent inhibition (when the conditioning pulse intensity was low). Kindling was found to increase paired-pulse facilitation. With the standard variable interval paradigm, these increases in facilitation masked the increases in suppression.

Amygdala↗
PubMed1995

Spatial learning and memory as a function of age in the dog.

Spatial learning and memory were studied in dogs of varying ages and sources. Compared to young dogs, a significantly higher proportion of aged dogs could not acquire a spatial delayed nonmatching-to-sample task. A regression analysis revealed a significant age effect during acquisition. Spatial memory was studied by comparing performance at delay interval of 20, 70, and 110 s. At short delays aged and young dogs were similar; at longer delays, errors increased to a greater extent in old than in young dogs; however this was not statistically significant. It was possible to identify 2 groups of aged animals, age-impaired and age-unimpaired. Several of the dogs were also tested on an object recognition memory task, which was more difficult to learn than the spatial task. The possibility that these findings are confounded by breed differences is considered. Overall, the present results provide further evidence of the value of a canine model of aging.

Aging↗
PubMed1994

(-)Deprenyl increases activities of superoxide dismutase (SOD) in striatum of dog brain.

Seven beagle dogs were administered sucrose (control animals) or different doses of (-)deprenyl orally by means of capsules for 3 weeks. Activities of Cu Zn-SOD and Mn-SOD were determined in striatum and hippocampus in these animals. There was a significant dose-dependent increase in activities of total as well as in both types of SOD enzymes in striatum but not in hippocampus. The results suggest that this monoamine oxidase B inhibitor can increase antioxidant enzyme activities in striatum but not in hippocampus in the dog, thus showing brain region selectivity. These results are in accordance with previously published observations in rats.

Animals↗
PubMed1994

Cognitive functions and aging in the dog: acquisition of nonspatial visual tasks.

Old, middle-aged, and young dogs were compared on discrimination and reversal learning and on acquisition of a delayed-nonmatching-to-sample (DNMS) test of recognition memory. DNMS acquisition was acquired more rapidly by young dogs. Reversal deficits were found between aged mixed-breed dogs and young beagles, but not between old and young beagles. Aged beagles also showed unexpected deficits in reward approach and object approach learning. Aged mixed-breed dogs did not show deficits in reward approach and object approach learning, but they learned the discrimination task more slowly than the age-matched beagles. A detailed analysis of response patterns indicated that once present, the development of side preferences contributed to deficits of old dogs in discrimination learning. In the discrimination reversal, old dogs were more persistent in responding to the previously rewarded stimulus object. Findings suggest that the dog, like other species, shows age-dependent deterioration in cognitive function, the extent of deterioration is a function of both task and previous experience, and at least part of the deterioration is a result of increased behavioral rigidity. Results also indicate that it is important to control for breed differences and previous experience.

Aging↗