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Biomedical subjects

D M Gash

Publications and source records attributed to D M Gash.

121 records · Page 7Linked to original sources
PubMed1981

Behavioral characteristics of vasopressin-deficient rats (Brattleboro strain).

A group of vasopressin-deficient rats (Brattleboro strain--DI) and a group of normal Long-Evans rats were successively evaluated on visual discrimination, olfactory discrimination, delayed alternation at short and long intertrial intervals (ITIs), approach-avoidance conflict in a straight runway, and open-field behavior. It was found that DI rats adapted more slowly than normal rats in the T-maze, in the straight runway, and they were slower to emerge into the open field. The DI rats were impaired relative to normal animals on the discrimination tasks (visual and olfactory), but they were not impaired on delayed alternation (at least for short ITIs). DI rats also showed better retention of the punishment effect in the approach-avoidance conflict test than normal animals. It is suggested that DI rats have defective reference-memory mechanisms, fairly intact working-memory processes and altered adaptability (timidity or cautiousness).

Animals↗
PubMed1975

Development of Rathke's pouch tissue transplanted into adult hypophysectomized female rats.

Rathke's pouch tissue, from rat embryos of 11-15 days' gestation, was microsurgically removed and transplanted into the hypothalamus of hypophysectomized adult females. The hosts were sacrificed 4 weeks later; brain and target organs were preserved for histological examination. Plasma samples were taken for the radioimmunoassay (RIA) of follicle stimulating hormone (FSH) and luteinizing hormone (LH). The implanted tissue invariably developed along certain lines. Undifferentiated primitive cells were found associated with nervous tissue, dense connective tissue, cartilage and glandular cells. In every age group, some implants became invasive, forming massive growths in the brain. These tumorous properties were principally associated (p less than 0.05) with tissue from 12-day embryos. Pituitary primordia from all ages demonstrated the ability to develop into functional adenohypophyseal tissue. Target organ stimulation indicated a secretion of corticotropin, thyrotropin and somatotropin. FSH and/or LH were detected by RIA in the plasma of 61% of the test animals. We suggest that this system offers unique opportunities for future investigations into the mechanisms that determine whether embryonic epithelial tissue will remain under normal growth control or will become tumorous or even cancerous.

Adenoma↗
PubMedDate not supplied

Hyperreflexive behavior in Brattleboro rats.

In two experiments we compared the size of the startle response elicited by shock and acoustic stimuli in animals having a congenital absence of vasopressin (Brattleboro rats) with closely related controls, which do synthesize vasopressin. The rats lacking vasopressin were hyperresponsive to both shock and acoustic stimuli. Inhibition of the acoustic startle by shock prestimuli also was greater in these animals. These results are consistent with reports which indicate that vasopressin attenuates responses to noxious stimuli.

Acoustic Stimulation↗
PubMedDate not supplied

Direct comparisons of CNS directed therapies are needed.

The review by Harbaugh describes new methods for delivering drugs to the diseases and damaged central nervous system. The potential of these methods, infusible pumps, implantable polymers, and neural transplants, is truly extraordinary. One can anticipate that many neurological disorders may be treated by these methods. Parkinson's disease, Alzheimer's disease, and other degenerative disorders are likely candidates. The question arises of how to rationally sort out the various claims as to which procedures and which approaches are the most effective and beneficial. As a first step, the relative risks as well as the benefits of these different drug delivery systems should be assessed by direct comparisons in the same animal model systems using objective criteria for evaluation. These comparisons would be best achieved by cooperative studies between the groups developing these techniques.

Animals↗
PubMedDate not supplied

Increased susceptibility to MPTP toxicity in middle-aged rhesus monkeys.

In the present study, age-associated effects of the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) administered via the right carotid artery were evaluated pre- and post-MPTP treatment in 26 female rhesus monkeys ranging in age from young adulthood to middle age (5 to 23 years old). A significant inverse correlation was seen between age and MPTP dose needed to produce stable, moderate parkinsonian features. Rhesus in the 5- to 9-year-old group required approximately three times the amount of MPTP as 20- to 23-year-old animals. Even though they received less MPTP, the older animals consistently displayed more severe bradykinesia, upper limb rigidity, and balance and gait abnormalities. Prior to MPTP treatment, home cage activity levels were strongly age dependent, with animals in the 10- to 19-year and 20- to 23-year groups displaying significantly less daytime activity than 5- to 9-year-old rhesus. Home cage activity levels tended to decrease in all age groups following MPTP treatment, but significant decreases were only measured in daytime activity in the 10- to 19- and 20- to 23-year age groups.

Age Distribution↗
PubMedDate not supplied

Age-related changes in potassium-evoked overflow of dopamine in the striatum of the rhesus monkey.

Rapid (5 Hz) chronoamperometric recordings using Nafion-coated carbon fiber electrodes (30-90 microns o.d.) combined with pressure-ejection of potassium from micropipettes were used to investigate potassium-evoked overflow of dopamine (DA) in the striatum of young (5 to 10 years old) and middle-aged (19 to 23 years old) anesthetized rhesus monkeys. The potassium-evoked DA-like signals from the 19- to 23-year-old animals were significantly lower in amplitude than those recorded in the young animals. In addition, the temporal dynamics of DA signals in the caudate nucleus of middle-aged animals were faster, while the time courses of the signals recorded in the putamen of middle-aged monkeys were significantly longer as compared to the signals recorded from young animals. Moreover, home cage activity levels of the middle-aged animals were significantly lower. Taken together, these data support age-related changes in the output of DA from DA fibers in the striatum of middle-aged monkeys.

Age Factors↗
PubMedDate not supplied

Animal models of age- and disease-related cognitive decline: perspectives on the models and therapeutic strategies.

The relative value of animals with memory impairments, due either to experimental lesions or aging processes, is dependent upon the specific hypothesis being tested. The experimental approaches described in the preceding reviews are valuable for basic studies on learning and memory in the mammalian brain. However, because of important differences between available model systems and human disease states, such as Alzheimer's disease, their use at present may be insufficient for understanding and developing treatment strategies for human cognitive dysfunctions. In this commentary, different aspects of animal models of memory dysfunction will be discussed relative to their ability to assess the structural and functional consequences of central nervous system (CNS) repair.

Aging↗
PubMedDate not supplied

Nerve growth factor receptor and choline acetyltransferase remain colocalized in the nucleus basalis (Ch4) of Alzheimer's patients.

Previous investigations have demonstrated an almost exclusive "coupling" between the receptor for nerve growth factor and cholinergic neurons within the basal forebrain. The present series of experiments were carried out to address two questions. First, what is the status of nerve growth factor receptor-containing neurons within the basal forebrain of patients with histopathologically confirmed diagnoses of Alzheimer's disease (AD)? More importantly, the second experiment assesses the degree to which the receptor for nerve growth factor and choline acetyltransferase remain colocalized within AD basal forebrain. A "decoupling" of this relationship, in which nerve growth factor receptors are no longer present upon magnocellular cholinergic neurons, would suggest that a loss of trophic support is functionally antecedent to the neuronal shrinkage and neuronal death seen in the basal forebrain in AD. Data obtained from six AD cases and four normal controls demonstrated an extensive reduction in number and shrinkage in size of nerve growth factor receptor containing neurons within the Ch4 region of the basal forebrain. Double label studies using either immunofluorescence or immunoperoxidase techniques demonstrated that the receptor for nerve growth factor and choline acetyltransferase remain colocalized in AD patients. This was true for neurons exhibiting either healthy or dystrophic morphological profiles. These data confirm previous studies, demonstrating that both a loss and shrinkage of cholinergic neurons occurs within the AD basal forebrain. The results of the present immunohistochemical investigation suggest that the degenerative changes associated with these neurons do not result from impaired trophic support related to a loss of NGF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗