Hypno-aversion treatment of nicotinism.
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Humans↗
Biomedical subjects
M M Miller
Publications and source records attributed to M M Miller.
Aging and long-term ovariectomy alter the cytoarchitecture of the hypothalamic-preoptic area of the C57BL/6J mouse.
Long-term ovariectomy attenuates several neuroendocrine-dependent changes in reproductive function of aging female rodents, but the sites affected and underlying mechanisms are not known. This study was designed to identify effects of aging on hypothalamic-preoptic neurocytoarchitecture and to determine whether long-term ovariectomy attenuated any of those changes. Coronal sections from midportions of the preoptic area (POA), suprachiasmatic nucleus (SCN) and arcuate nucleus (ARC) were examined by quantitative light microscopy in young (5 month) and old (18-20 months) intact mice and in old mice which had been ovariectomized at 6 months of age. Neuronal density in old intact mice decreased in both ARC and POA (30%; p less than 0.05), but no significant decrease occurred in SCN. Total perikaryal area decreased only in ARC (10%; p less than 0.05), while area of perikaryal nuclei did not change in any region. Area of nucleoli increased (13%; p less than 0.005) in all three regions of old intact and old ovariectomized mice. Neither density nor size of glia changed with age. Density of blood vessels increased strikingly in ARC (150%; p less than 0.05), and in POA (30%; p less than 0.05), but not significantly in SCN of old mice. Long-term ovariectomy did not prevent any of these changes; indeed, it promoted the decline of neuronal density in SCN (40%; p less than 0.05) and neuronal area (15%; p less than 0.05) in POA. Reductions in neuronal density were not explained by expansion of the SCN or peri-ARC or peri-POA regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Loss of LH-RH neurons in the rostral forebrain of old female C57BL/6J mice.
This study reports the quantitative immunohistochemical distribution of luteinizing hormone-releasing hormone (LH-RH) neurons within the rostral forebrain of young (5-6 month) and old (26-28 month) C57BL/6J mouse. Old mice demonstrated a significant (18%) loss of LH-RH-containing neurons (p less than 0.001, ANOVA). The most striking losses involved the preoptic area (24%) and more rostral regions (26%). The presence of pituitary or mesenteric tumors in older mice did not affect the density of LH-RH neurons. These observations indicate that LH-RH neurons comprise part of the neuronal population previously reported to be reduced in the preoptic area of older mice (4).
Aging↗
Loss during aging of beta-endorphinergic neurons in the hypothalamus of female C57BL/6J mice.
Beta-endorphin (B-EP) content is often reduced in hypothalami of aging rodents. The objective of this study was to determine whether reduced B-EP content is associated with a reduced number of B-EP immunoreactive neurons. Serial coronal sections extending from the caudal hypothalamus through the retrochiasmatic area were examined by quantitative light microscopy in mature (5-6 month) and senescent (24-28 month) mice that had been ovariectomized 1 week earlier and injected with colchicine 24-48 h before sacrifice. Old mice were acyclic. As expected, B-EP immunoreactive cell bodies were restricted to the region of the arcuate nucleus. There was a 35% loss of B-EP immunopositive neurons in old, macroscopically disease-free animals. By contrast, some old animals with pituitary tumors had no loss of B-EP neurons. These results suggest that a subpopulation of B-EP neurons either die or stop synthesizing detectable concentrations of B-EP in aged mice. The basis for the absence of reduced B-EP neurons in some mice with pituitary tumors is unclear, but this observation underscores the importance of distinguishing age-related changes associated with diseases of aging from those that are independent of such diseases.
Aging↗
Aging changes in the beta-endorphin neuronal system in the preoptic area of the C57BL/6J mouse: ultrastructural analysis.
In hypothalami of aging rodents, beta-endorphin (beta-EP) neuron number and content are reduced. The objectives of this study were: first, to analyze ultrastructurally the population of neuronal elements in a selected region of the preoptic area (POA) in young and old mice; second, to study the beta-EP neuronal system in the same region to determine whether or not this population remains stable with age. Vibratome sections from the most caudal POA through the diagonal band of Broca were examined by light microscopy and immunocytochemistry in mature, cycling (5-6 months old) and old, acyclic, disease-free (24-26 months old) mice. A subset of beta-EP-like perikarya and associated structures was observed in the periventricular POA. When this subregion was examined at the ultrastructural level, there was a significant decrease in the number of recipient dendrites [3.78 +/- 0.04 SEM/micron 2 young vs. 0.82 +/- 0.03/micron 2 old; p < 0.007, analysis of variance (ANOVA)], but a significant increase in the number of nonmyelinated axons (20.0 +/- 2.6/micron 2 young vs. 26.8 +/- 0.7/micron 2 old; p < 0.05). Immunolabeled terminals that contained a synapse comprised 2.56 +/- 0.08% of all terminals with synapses in young mice but only 0.34 +/- 0.04% in old ones when corrected for surface area examined (p < 0.03). A significant age-related loss was also observed in the nonmyelinated beta-EP-labeled axon population (1.50 +/- 0.10% young vs. 0.40 +/- 0.01% old; p < 0.009, ANOVA). We conclude that there are critical changes in the microenvironment of the POA in old, noncycling female mice that are likely to affect neuron function.
Aging↗
Ovariectomy and age alter gonadotropin hormone releasing hormone-noradrenergic interactions.
The noradrenergic (NA) system influences gonadotropin hormone releasing hormone (GnRH) neurons resulting in the luteinizing hormone surge. Direct neuroanatomical interactions between preoptic area (POA) GnRH neuronal elements and NA [i.e., dopamine-beta-hydroxylase (DBH)] terminals; effects of short-term ovariectomy (S-OVX) on these interactions; and the stability of these interactions with age were studied in young (5-month-old) proestrous, 5-month-old S-OVX (6d), old (24-month-old) constant diestrous, and 24-month-old long-term (L)-OVX mice. Proestrous females demonstrated direct interactions between NA terminals and GnRH neuronal elements. The percentage of GnRH dendritic profiles contacted by DBH terminals at proestrous (6.96 +/- 1.07%) did not differ versus young S-OVX females (4.55 +/- 0.91%). No GnRH-NA interactions were observed in old mice. S-OVX resulted in a decrease in DBH terminals but an increase in dendrite and nonmyelinated axon number versus young proestrous females (p < or = 0.05 ANOVA). Findings show direct GnRH-DBH interactions, confirm S-OVX effects on neural ultrastructure, and demonstrate some S-OVX changes resembling those in older mice. L-OVX failed to prevent aging changes. Diminished capacity to produce normal estrous cycles in aging females could result in part from absence of direct GnRH-DBH interactions.
Age Factors↗
Methylene blue but not indigo carmine is toxic to human luteal cells in vitro.
Methylene blue (MB) is reported to be teratogenic when injected intra-amniotically. Indigo carmine (IC) appears to be a safe alternative. To determine if MB has potential detrimental effects on ovarian tissue, we compared the effect of MB and IC on human granulosa luteal cell (GC) function in vitro. Human oocyte-cumulus complexes were obtained during in vitro fertilization cycles and one to three were placed in an organ culture dish. After insemination with sperm, oocytes were removed the day after retrieval and the attached GC were washed daily for 3 more days by changing 2 mL of culture medium. All the dishes were treated with human chorionic gonadotropin (hCG) for the next 24 h and progesterone (P) production during this interval was taken as baseline. Test chemicals were added with hCG for the next 48 h with daily media changes. The P production during the last 24 h of chemical treatment was expressed as a percentage of the baseline. MB significantly reduced P production whereas IC did not appear to have any effect. Moreover, under inverted microscopy more than 90% of the GC cells contained several small bluish intracellular granules when exposed to 0.01% MB but not 0.01% IC. These results indicate that MB may be taken up and processed by GC cells and inhibits P production. This finding adds to previous reports on the use of in vitro GC assay to identify potential reproductive toxicants. The clinical significance of this preliminary study needs further investigation.
Cells, Cultured↗
Estrogen, the ovary, and neutotransmitters: factors associated with aging.
Our studies in the C57BL/6J mouse have been designed to examine the interactions of aging and the ovary, and their mutual effects on neuroendocrine function. In the pituitary, ovarian status and not age determines responsiveness to gonadotropin hormone releasing hormone (GnRH), but estrogen (E2) is an important mediator in CNS changes, and removal of the ovary (OVX) is deleterious to the neuroendocrine hypothalamus. OVX for just six days in young animals results in synaptic loss between noradrenergic terminals and gonadotropin hormone releasing hormone (GnRH) neurons. Long-term OVX, hypothesized to protect against neuroendocrine aging, fails to guard against any studied age-related changes. Some age-related changes occur as early as midlife. Although neuron number remains constant at middle age, opiatergic neurons undergo significant functional changes by producing opiate antagonist peptides. This change appears to be caused by alterations in the prohormone convertases, which cleave propeptide to peptide. Altered peptides may trigger the loss of reproductive capacity. The midlife shift in opiate peptide production is a component of natural developmental processes that begin in the neonate and continue through old age. In the cholinergic system, E2 mediates numbers of cholinergic receptors, cholinergic neurons, and cholinergic-modulated memory systems in both young and old animals. Regardless of age, ovarian steroids, if present at physiologic levels, are beneficial to the neuroendocrine CNS, and long-term deprivation from ovarian-produced factors is deleterious in the systems we have examined. Our studies have shown that deprivation from ovarian steroid hormones in the female appears to be a major factor in the health of the CNS and in events associated with aging.
Aging↗
Identification, inheritance, and linkage of B-G-like and MHC class I genes in cranes.
We identified B-G-like genes in the whooping and Florida sandhill cranes and linked them to the major histocompatibility complex (MHC). We evaluated the inheritance of B-G-like genes in families of whooping and Florida sandhill cranes using restriction fragment patterns (RFPs). Two B-G-like genes, designated wcbg1 and wcbg2, were located within 8 kb of one another. The fully sequenced wcbg2 gene encodes a B-G IgV-like domain, an additional Ig-like domain, a transmembrane domain, and a single heptad domain typical of alpha-helical coiled coils. Patterns of restriction fragments in DNA from the whooping crane and from a number of other species indicate that the B-G-like gene families of cranes are large with diverse sequences. Segregation of RFPs in families of Florida sandhill cranes provide evidence for genetic polymorphism in the B-G-like genes. The restriction fragments generally segregated in concert with MHC haplotypes assigned by serological typing and by single stranded conformational polymorphism (SSCP) assays based in the second exon of the crane MHC class I genes. This study supports the concept of a long-term association of polymorphic B-G-like genes with the MHC. It also establishes SSCP as a means for evaluating MHC genetic variability in cranes.
Amino Acid Sequence↗
A complex alloantigen system in Florida sandhill cranes, Grus canadensis pratensis: evidence for the major histocompatibility (B) system.
The B blood group system constitutes the major histocompatibility complex (Mhc) in birds. The Mhc is a cluster of genes largely devoted to the processing and presentation of antigen. The Mhc is highly polymorphic in many species and, thus, useful in the evaluation of genetic diversity for fitness traits within populations of a variety of animals. Correlations found between particular Mhc haplotypes and resistance to certain diseases emphasize the importance of understanding the functional significance of diversity of the Mhc, particularly in species threatened with extinction. As part of studies focused on genetic diversity in wild birds, serological techniques were used to define a highly polymorphic alloantigen system in seven families of Florida sandhill cranes (Grus canadensis pratensis). The results of analyses with antisera produced within the crane families and with chicken Mhc antigen-specific reagents revealed a single major alloantigen system that is likely the Mhc of the Florida sandhill crane. Preliminary experiments indicate that these crane alloantisera will provide a means of defining the Mhc in other species of cranes.
ABO Blood-Group System↗
Loss of fusion and the development of A or V patterns.
To test the hypothesis that loss of fusion predisposes the ocular motor system to the development of A or V patterns, we reviewed the pre- and postoperative courses of patients with intermittent exotropia overcorrected with horizontal muscle surgery. Of 332 patients who had surgery, 21 experienced at least 1 month of consecutive esotropia. An equal number of age-matched patients who maintained fusion postoperatively served as controls. No patient in either group had a preoperative A or V pattern. At the first return visit, at least 4 weeks postoperatively, 4 (19%) of the 21 patients with consecutive esotropia showed an A or V pattern, whereas none of the 21 control patients did so. At the end of follow up (mean of 27 months for patients with consecutive esotropia and 29 months for controls), 9 (43%) of the 21 patients with consecutive esotropia showed an A or V pattern versus 1 (5%) of the 21 controls. These findings strongly suggest that loss of fusion is instrumental in the development of A or V patterns, consistent with "sensory torsion" theory of A and V pattern development.
Child, Preschool↗