Barbara J. Davis

Complex maze performance in young and aged rats: response to glucose treatment and relationship to blood insulin and glucose.

In aged rats and humans, impaired glucose regulation has been correlated with poor memory performance, and glucose treatment can result in improved performance. We tested this glucose hypothesis with rats in a 14-unit T-maze that has provided robust evidence of age-related performance decline. Aged (24-25 month) and young (6-7 month) male F-344 rats were pretrained for one-way active avoidance before receiving complex maze training (4 daily trials over 5 days) with the contingency of moving through each of 5 segments to avoid footshock. Ten min before daily training, aged rats received either saline or glucose in doses of 10, 100, or 500 mg/kg IP, while young rats received saline. Significant (ps less than 0.05) age-related increases in errors, runtime, and shock duration were observed. Glucose treatment had no significant effect on the number of maze errors committed; however, performance variables such as runtime and shock duration appeared to be reduced in rats receiving glucose. About 4-6 weeks later, a sample of these rats was fasted overnight, injected IP with glucose (150 mg/kg), and bled at various postinjection intervals to obtain estimates of blood glucose and insulin levels. Significant correlations (ps less than 0.05) were observed between maze errors and baseline glucose levels, r(21) = -.62, and peak glucose response, r(19) = .49. However; within the aged group, significant correlations (ps less than 0.01) with maze errors emerged only for baseline glucose, r(13) = -.69, and peak insulin response, r(13) = -.65. Thus, regulation of insulin, but not glucose, appeared related to learning abilities among aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological and functional aspects of pancreatic islet innervation.

Pancreatic islets are collections of 4 functionally-related endocrine cells distributed nonrandomly in the pancreas. Their major physiological actions center about the regulation of metabolic homeostasis. Experimental evidence shows that, in addition to circulating substates, the islets are controlled by outflow from the central nervous system communicated through autonomic nerves. Islet cells also interact with one another via hormonal messengers and, possibly, electrotonic impulses producing a complex--yet well-controlled--system for the integration of numerous types of signals. This paper is a brief review of some of the numerous interactions between the autonomic nervous system and the endocrine pancreas. Particular emphasis is placed on the role of recently discovered autonomic factors and newly recognized autonomic centers in the brain.

Localization of motilin-containing cells in the intestinal tract of mammals: A further comparison using region-specific motilin antisera

Abstract Region-specific antimotilin sera were used to investigate the presence of motilin-containing cells in the intestines of humans, dogs, cats, and rats. Motilin-containing cells were observed in the duodenal mucosa of humans, dogs, and cats. However, motilin-like immunoreactivity was not detected in any region of the rat intestinal tract. Results of this study suggest that motilin is not present in the intestinal tract of the rat or that it exists in a storage from that differs significantly from that of other species.

Effects of lesions of hypothalamic catecholamines on blood pressure, fluid balance, vasopressin and renin in the rat

Fluid balance, systolic blood pressure (BP) and serum vasopressin (VP) and renin activity (SRA) in the basal state and in response to blood volume depletion were examined in unanesthetized rats previously given intrathecal 6-hydroxydopamine (6-OHDA) to destroy catecholaminergic (CA) input to supraoptic nucleus (SON). Sham-operated rats, unoperated ad libitum hydrated rats and rats undergoing 4 days of water deprivation served as controls. The 6-OHDA lesion resulted in adipsia, a failure to conserve administered fluids and a decrease in systolic BP. Despite decreased blood volume secondary to dehydration, and decreased systolic BP, the 6-OHDA group failed to show the expected increase in serum VP. However, when blood volume was further decreased following intraperitoneal polyethylene glycol, lesioned rats showed robust VP and SRA responses. Thus, CA input to critical target areas in the hypothalamus may be necessary for maintenance of sensitivity to stimuli that normally elicit VP release. Decreased systolic BP following 6-OHDA lesions most likely results from dehydration coupled with inadequate VP responses.

Localization of vasopressin-neurophysin and norepinephrine in the supraoptic nucleus of spontaneously hypertensive rats

Histological analysis of the catecholaminergic innervation of vasopressin neurons in the supraoptic nucleus (SON) was performed using catecholamine histofluorescence and immunocytochemistry of vasopressin specific neurophysin (VP-NP) in order to determine if spontaneously hypertensive rats (SHR) demonstrate alterations in the relationship between these two types of chemically defined neurons. Chronically hypertensive SHRs showed an increased density of catecholamine fluorescence particularly in the dorsal part of the SON in comparison to age-matched, normotensive, Wistar-Kyoto (WKY) rats, but not in comparison to age-matched Wistar rats. In addition, there was an increase in the area of distribution of VP-NP immunopositive neurons such that they extended into the dorsal portion of the nucleus in the SHR compared to the WKY. Comparator bridge analysis of immunocytochemical staining and catecholamine histofluorescence revealed a precise overlap of the two patterns in SHR. Thus, the more extensive distribution of catecholamine fluorescence in the dorsal SON in the SHR compared to WKY paralleled the more extensive distribution of VP neurons in this region. Quantitative analysis of the relative percentage of SON neurons which were VP-NP positive indicated that the increased representation of VP-NP positive neurons in the dorsal portion of the nucleus reflected a greater distribution of the VP-NP cell population throughout the SON rather than an increase in the number of VP-NP neurons in the SHR. In young SHRs (5 weeks old) the catecholamine fluorescence pattern in the SON was considerably smaller than that observed in older SHRs. This low density pattern, however, was comparable to that observed in young WKYs. Thus, the catecholamine fluorescence in the SON apparently increases in the SHR in parallel with the development of the hypertension. This observation and the finding of comparable catecholamine fluorescence in Wistars and SHRs suggest that the altered catecholamine innervation of VP neurons observed in chronically hypertensive SHRs is not causal to the hypertension but may reflect a response to the elevated blood pressure. A marked increase in the catecholamine innervation of cerebral arteries was also noted.

Effects of substantia nigra lesions on the volumes of A, B, and D cells and the content of insulin and glucagon in the rat pancreas.

SummaryThe effects of substantia nigra lesions on the volume densities of islet cells and on the content of insulin and glucagon in the pancreas were examined using five groups of age-matched, Sprague-Dawley rats. Two groups received bilateral substantia nigra lesions using intrathecal injections of either a low (6 μg/hemisphere) or a high (12 μg/hemisphere) dose of 6-hydroxydopamine. Rats given sham lesions served as controls for the effects of the neurotoxic drug. These three groups, plus a fourth consisting of unoperated controls, were provided with a high-fat diet to minimize lesion-induced alterations of food intake and body weight. Eleven weeks after lesion placement, tissue was collected from all animals for the assessment of islet cell volume densities and the pancreatic content of insulin and glucagon. Plasma samples also were obtained to determine the levels of glucose, insulin, and glucagon. Data from those animals were compared with that obtained from a fifth group, termed “pre-lesion controls”, sacrificed at the beginning of the experiment. Linear-scan morphometry documented an increase of B-cell volume density in the pancreas of non-lesioned rats over the 11-week period (p<0.05). However, the volume density of B cells in the pancreas of lesioned animals did not increase compared with that of pre-lesion controls. In terms of A or D cells, no significant differences of volume density were found between the five groups. Compared with that of the pre-lesion controls, pancreatic insulin and glucagon content increased in the lesioned and neurally-intact animals. However, the molar ratio of those hormones in the pancreas of lesioned rats remained similar to that of pre-lesion controls. The current findings suggest that the substantia nigra is an important autonomic area involved in controlling islet growth and development, and possibly islet function as well.

Altered Catecholamine Innervation of the Supraoptic Nucleus in the Nephrogenic Diabetes insipidus Mouse

Fluorescence histochemical and immunocytochemical techniques were used to investigate morphologic correlates of the relationship between catecholamine varicosities and vasopressin-containing perikarya in an animal model of vasopressin excess, the nephrogenic diabetes insipidus mouse. Our results show hypertrophy and increased immunoreactivity in vasopressin neurons in these mice were accompanied by a marked increase in the density and to some extent the fluorescence intensity of catecholamine varicosities within the supraoptic nucleus. These results further support the concept of functional interactions between catecholamine and vasopressin neurons and raise the possibility that the target neuron, or one of its products, perhaps vasopressin, either exerts a trophic influence on the catecholamine innervation pattern of the supraoptic nucleus or enhances catecholamine content in existing fibers and terminals.

Alterations of pancreatic islet size and growth following substantia nigra lesions in the rat

Lesions of certain autonomic centers in the brain are known to alter feeding behavior, body weight, and influence the morphology and function of the pancreatic islets. Because marked reductions of food intake and body weight have been reported following damage to the substantia nigra (SN), we investigated the role of this brain area as a potential regulator of the endocrine pancreas. Rats were given bilateral SN lesions using the neurotoxin 6-hydroxydopamine (6-OHDA) at a dose of either 6 or 12 micrograms/hemisphere. Animals given sham lesions served as controls. Both the control and experimental rats were placed on a high-fat diet to minimize lesion-induced reductions of food intake and body weight. Eleven weeks following lesion placement, pancreatic tissues were collected and islet size and volume density were determined using point-counting stereological analyses. At the time of tissue collection, the body weights of control and experimental rats were comparable. Rats with SN lesions exhibited a reduction of pancreatic islet size and volume density, when compared with that of sham-lesioned controls. Moreover, the islets of SN-lesioned rats were comparable in size and volume density to that of younger animals. Hence, these observations suggest that damage to the SN produces an overall impairment of islet growth independently of changes in body weight.

Plasticity of Neuronal Interactions: Monoamines and Neuropeptides

Monoamines and neuropeptides are distributed widely throughout the mammalian brain. In many brain regions these two classes of neuroactive substances appear intermixed, which suggests the possibility of functional interactions. We have attempted to define the precise relationship between selected monoamine and peptide neurons in order to provide a working model of neuronal interactions. The systems chosen include the classic endocrine peptides of the magnocellular hypothalamus, vasopressin and oxytocin, and noradrenergic afferents from the reticular formation of the medulla.

Neuroendocrine Effects of Lifelong Dietary Restriction by Intermittent Feeding in Mice

Lifelong dietary restriction has been shown to increase mean and maximum life span and to delay the onset of pathophysiologic changes associated with aging in rodents (Barrows and Kokkonen, 1978). The mechanisms underlying the modulation of aging by dietary restriction remain unknown. Based on studies using several levels of dietary restriction in mice, Weindruch et al. (1986) suggested that increased metabolic efficiency may be related to longevity, since the longest-lived mice at each level of dietary restriction studies also were the heaviest. Although a number of studies support the hypothesis that increased body weight is associated with increased longevity in dietarily restricted rodents, (reviewed by Ingram and Reynolds, 1987), the relationship between body weight and life span is complex, and it is difficult to make generalized statements relating longevity to body weight.