Biomedical subjects

J P Herman

Publications and source records attributed to J P Herman.

131 records · Page 8Linked to original sources

PubMedDate not supplied

Microcomputer-based three-dimensional reconstruction of in situ hybridization autoradiographs.

A number of software routines were written for the public domain Macintosh-based video-densitometry program, Image, to facilitate in situ hybridization analysis. These routines utilize fiducial marks drilled in unused portions of the brain to rotate high-magnification images of individual sections so that they may be placed in register. The regions of interest within the registered sections are outlined and intermediate sections interpolated to produce a data set representing a three-dimensional volume. This shell is then filled with the original density data obtained with one or more in situ hybridization probes. The final object can be viewed in various degrees of translucency and examined from different angles or computationally resectioned to yield new information concerning activity changes within the region and relationships between reactive sites. These static images can be collected and rapidly displayed as a movie. These routines have been used in this paper to display the differential hybridization of three different mRNA probes in the hypothalamic paraventricular nucleus.

Animals↗

PubMedDate not supplied

Hypothalamo-pituitary-adrenocortical dysregulation in aging F344/Brown-Norway F1 hybrid rats.

Hypothalamo-pituitary-adrenocortical (HPA) axis aging was studied in young (3 mo), middle aged (15 mo) and aged (30 mo) F344/Brown Norway hybrid rats. This strain was selected to obviate HPA-relevant pathologies found in other aging models. Aged, unstressed rats showed enhanced central HPA drive, marked by elevated ACTH release and decreased pituitary proopiomelanocortin and corticotropin-releasing factor receptor 1 (CRH-R1) mRNAs. Acute corticosterone responses to spatial novelty were exacerbated in aged rats; however, responses to restraint or hypoxia were not affected. Chronic stress exposure also differentially increased HPA drive in aged animals, marked by elevated paraventricular nucleus CRH peptide levels and pituitary proopiomelanocortin mRNA. Plasma ACTH and pituitary POMC and CRH-R1 mRNA expression in middle-aged rats were intermediate those of young and aged animals. Middle-aged animals responded to chronic stress with disproportionate increases in CRH mRNA levels, and increased corticosterone secretion following hypoxia but not novelty. The results suggest a gradual increase in HPA tone across the aging process, culminating in marked hyperresponsivity to both acute and chronic stress in senescence.

Acute Disease↗

PubMedDate not supplied

Up-regulation of alpha1D Ca2+ channel subunit mRNA expression in the hippocampus of aged F344 rats.

There is growing evidence that alterations in calcium (Ca2+) homeostasis may play a role in processes of brain aging and neurodegeneration. There also is evidence that some of the altered Ca2+ homeostasis in hippocampal neurons may arise from an increased density of L-type voltage sensitive Ca2+ channels (L-VSCC). In the present studies, we tested the possibility that previously observed increases in functional L-VSCC with aging might be related to up-regulated gene/mRNA expression for Ca2+ channel subunits. A significant aging-related increase in mRNA content for the alpha1D subunit of the L-type VSCC was observed in hippocampus of aged F344 rats (25 months old) relative to young (4 months old) and middle-aged animals (13 months old), as assessed by both in situ hybridization analyses (densitometry and grain density) and ribonuclease protection assay (RPA). In RPA analyses, the alpha1C subunit mRNA also showed a significant increase in 25-month-old rats. No age changes were seen in mRNA for the beta1b subunit of VSCC or for GAPDH, a standard control. The clearest increases in alpha1D mRNA expression were observed in subfield CA1, with little or no change seen in dentate gyrus. Although these results alone do not demonstrate that mRNA/gene expression changes contribute directly to changes in functional Ca2+ channels, they clearly fulfill an important prediction of that hypothesis. Therefore, these studies may have important implications for the role of gene expression in aging-dependent alterations in brain Ca2+ homeostasis.

Aging↗

PubMedDate not supplied

Aberrant stress response associated with severe hypoglycemia in a transgenic mouse model of Alzheimer's disease.

Patients with Alzheimer's disease (AD) exhibit alterations in glucose metabolism and dysregulation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) neuroendocrine system. The mechanisms responsible for these alterations and their possible contributions to the neurodegenerative process in AD are unknown. We now report that transgenic mice expressing a mutant form of human amyloid precursor protein (APP) that causes inherited early-onset AD exhibit increased sensitivity to physiological stressors, which is associated with aberrancies in HPA function and regulation of blood glucose levels. Specifically, APP mutant mice exhibit severe hypoglycemia and death following food restriction, and sustained elevations of plasma glucocorticoid levels and hypoglycemia following restraint stress. The alterations in HPA function and glucose regulation were evident in relatively young mice prior to overt deposition of amyloid beta-peptide (A beta). However, diffuse accumulations of A beta were present in the hypothalamus of older mice, suggesting a role for soluble forms of A beta in dysregulation of HPA function. Our data demonstrate disturbances in neuroendocrine function in APP mutant mice similar to those seen in AD patients. These impairments in stress response, glucocorticoid signaling, and regulation of blood glucose should be considered in interpretations of data from past and future studies of APP mutant mice.

Alzheimer Disease↗

PubMedDate not supplied

Catecholamine turnover measurement and ACTH-induced short-term changes of catecholamine levels in individual brain nuclei.

The effect of acute ACTH treatment on catecholamine content of various brain nuclei was followed by radioenzymatic assay. The hormonal treatment employed affected catecholamine levels only in some hypothalamic nuclei and in the locus coeruleus. Some effects could be detected as rapidly as 10 min after the injection of the hormone. Employing alpha-methyl-para-tyrosine, catecholamine turnover in individual nuclei was estimated, and shown to be quite variable from one area to the other. However, severe limitations seem to exist in vivo, which restrict the feasibility of this approach to basal or chronic situations.

Adrenocorticotropic Hormone↗