Search PubMed⌕ Search

Biomedical subjects

C E Finch

Publications and source records attributed to C E Finch.

At least 181 records · Page 10Linked to original sources
PubMed1983

[3H]spiperone binding sites in rat primary glial cultures, C6 glioma, and B104 neuroblastoma.

Binding sites for [3H]spiperone were detected on membranes from primary glial cultures from neonatal rat cortex and striatum and from the C6 glioma cells. [3H]Spiperone binding was displaceable by d-butaclamol. However, competition studies suggest that [3H]spiperone binding to primary glial cultures was mainly to serotonergic sites, and binding to the C6 glioma was alpha-adrenergic. No specific binding was detected to membranes from B104 neuroblastoma cells. Although [3H]spiperone binding to glial sites on whole striatum under generally used conditions is small (about 10%), the striatal glial hyperactivity that is often associated with neuronal degeneration could lead to an overestimation of presumed neuronal binding sites for dopaminergic ligands.

Animals↗
PubMed1983

Restoration of ovulatory cycles by young ovarian grafts in aging mice: potentiation by long-term ovariectomy decreases with age.

The relative contributions of ovarian and hypothalamic-pituitary factors to the anovulatory status of aging mice were evaluated by measuring the capacity of mice to resume ovulatory cyclicity after receiving young ovaries under the renal capsule. Young grafts partially restored cyclicity if old hosts were acutely ovariectomized but almost fully restored cyclic ovulatory function if the old hosts had been ovariectomized early in adulthood. With advancing age, however, the efficacy of the grafts declined progressively in both acute and long-term ovariectomized groups. These data show that both ovarian and hypothalamic-pituitary aging contribute to the etiology of anovulation. Although chronic withdrawal from ovarian secretions retards the age of onset of hypothalamic-pituitary aging, the duration of this ameliorative effect is limited by progressive ovary-independent neuroendocrine dysfunction.

Aging↗
PubMed1983

Imminent oocyte exhaustion and reduced follicular recruitment mark the transition to acyclicity in aging C57BL/6J mice.

Quantitative cytological analyses of aging C57BL/6J mouse ovaries revealed that the populations of primordial and growing follicles were nearly exhausted by 13-14 months, the average age of ovulatory failure. Anovulatory animals of this age had, on the average, half the follicle number of their counterparts which were still ovulating. This result suggests that follicular depletion is a factor which contributes to the loss of ovarian cyclicity during aging. However, the considerable overlap of follicle number between the two groups suggests that other, possibly extraovarian, factors also influence the loss of ovulatory function. Although the numbers of follicles recruited for growth was much lower in ovaries from old cycling animals, the number of ova shed cyclically was generally within the range of younger individuals. The observed reduction in incidence of morphological atresia among medium-sized follicles may explain how ovulatory constancy is maintained virtually throughout the cyclical life of the ovary.

Aging↗
PubMed1983

Aging and the regulation of luteinizing hormone in C57BL/6J mice: impaired elevations after ovariectomy and spontaneous elevations at advanced ages.

The effects of age on the elevations of plasma luteinizing hormone (LH) after ovariectomy were studied in C57BL/6J mice. In longitudinal studies, mice ovariectomized at 4-6 months and sampled serially reached maximum plasma LH (200-300 ng/ml) after 1 month; these elevations were maintained to at least 15 months of age, when most intact mice have ceased cycling and have persistent vaginal cornification (PVC). In contrast, mice ovariectomized at 15 or 21 months had smaller LH elevations (to 150 ng/ml) 1 or 2 months after ovariectomy, as compared to younger (5- or 11-month-old) cycling mice whose LH was ca. 200 ng/ml 1 month after ovariectomy. The maintenance of LH elevations in chronically ovariectomized mice suggests that the smaller LH elevations in acutely ovariectomized mice of the same age may be an ovary-dependent aging phenomenon. Pilot studies detected no age effects on plasma LH turnover. Intact 20- to 26-month-old mice with leukocytic vaginal smears, low plasma estradiol (E2) and low progesterone had initially elevated plasma LH (ca. 125 ng/ml), if gross pathologic lesions were not present at necropsy. In contrast, old mice with cornified vaginal smears had higher plasma E2 and low (normal) plasma LH. The low plasma progesterone and elevated LH in older mice with leukocytic smears argues against a pseudopregnant status. Old mice of all vaginal smear types with pathologic lesions had low LH. Ovariectomy did not yield further increases of LH in old mice. The spontaneous elevation of plasma LH to ovariectomized levels in old intact mice with leukocytic vaginal smears and reduced plasma E2 implies that C57BL/6J mice eventually undergo ovarian changes analogous to menopause in humans.

Age Factors↗
PubMed1983

Graafian follicle growth and replacement in anovulatory ovaries of ageing C57BL/6J mice.

The growth of preantral follicles and replacement of large Graafian follicles was studied in reproductively senescent C57BL/6J mice immediately after the loss of oestrous cyclicity when the ovary is approaching exhaustion of its follicular reserve. Granulosa cells were labelled in vivo by injection of tritiated thymidine and were evaluated by autoradiography. At 1 h after injection, labelling was confined almost exclusively to the cumulus and neighbouring cells whereas the distribution of labelled granulosa cells in preantral follicles was approximately uniform. The proportion of labelled mural cells in Graafian follicles rose from initially low values to maximal levels 3 days later; this suggested that those follicles that were Graafian at the time of injection had been replaced by recruitment of preantral stages. The rate of growth of preantral follicles was similar in senescent anovulatory mice and in young adult animals. A simple model was constructed to illustrate how persistent vaginal cornification in ageing mice is sustained by a stream of Graafian follicles and why some of the latter did not respond fully to an ovulatory dose of hCG.

Aging↗
PubMed1982

Aging and uterine growth during implantation in C57BL/6J mice.

Uterine growth during implantation was compared in C57BL/6J mice aged 3-7 mo vs. 11-12 mo. All mice had given birth to at least one previous litter. Older mice had smaller uteri during early gestation (3 to 10 days post coitum) as measured by DNA content, although wet weight and protein were generally similar in both age groups. However, there were no age effects on uterine growth during implantation, as measured by the increments of DNA, as well as protein and wet weight per implantation site (decidual swelling) on days 6-10. These data are discussed in terms of the major increase in fetal death and resorptions in older mice subsequently observed by day 12-13. Larger age-related impairment of the artificially-induced decidual response is also considered. We conclude that impairments of the artificially induced decidual response do not predict the extent of decidual responses during pregnancy in aging mice.

Aging↗
PubMed1982

A longitudinal study of estrous cyclicity in aging C57BL/6J mice: I. Cycle frequency, length and vaginal cytology.

Cycle frequency, length, and vaginal cytology were measured longitudinally in three cohorts of singly housed virgin mice staggered across a 3-year interval. The age profiles of these parameters were qualitatively similar, but quantitatively different, among cohorts. Cycle frequency was initially low (Phase I), due to prolonged cycles and late-starting cycles, and did not peak (Phase II) until mice were 3-5 months old. Phase II lasted for 7-10 months, depending on the cohort. Thereafter cycle frequency declined steadily (Phase III). The average age of cessation of cyclicity varied among cohorts, occurring between 13 and 16 months of age. Age changes in cycle length paralleled those of cycle frequency. During Phase II, median cycle length was less than 5 days and variance was lowest. During Phases I and III, variance was about twofold greater and median cycle length was greater than 5 days. Although median cycle length remained stable for several months during Phase II, the peak period of 4-day cycles was much shorter. In all cohorts, 4-day cycles did not peak until 7-8 months of age and began to decline by 9 months. The decrease in 4-day cycles was associated with a progressive lengthening of cycles-first from 4 to 5 days, then to longer cycles. The fraction of cycles with extended cornification (greater than 2 days) increased with advancing age from less than 0.35 during the initial period of cycle lengthening to a maximum of 0.60. The observation that the initial phase o cycle prolongation was not usually associated with extended cornification is consistent with earlier evidence that this period is characterized by a delayed, rather than prolonged, preovulatory rise of estradiol. However, the increased fraction of prolonged cycles with extended cornification at later ages suggests that the preovulatory elevation of estradiol may ultimately be prolonged.

Aging↗
PubMed1982

Age-correlated loss of dopaminergic binding sites in human basal ganglia.

Human caudate nucleus, putamen, substantia nigra, and nucleus accumbens were analyzed for the effects of age on dopaminergic binding sites. Decreases in the number of dopaminergic binding sites were detected with age in caudate nucleus (44 specimens from three sample groups) and substantia nigra (n = 12). In caudate nucleus, the decline in [3H]2-amino-6, 7-dehydroxy-1, 2, 3, 4-tetrahydronaphthalene sites was three times greater than for [3H]spiperone, but age changes were significant in only two of the three sampling groups. No age changes in binding were detected in the putamen (n = 44) or nucleus accumbens. Age, sex, and tissue source all significantly contributed to variance. However, cause of death, time from death to tissue freezing, and length of storage did not influence dopaminergic binding in the caudate nucleus or putamen. Relative to the life-span, the age-correlated decrease in dopaminergic binding sites of human brain approximates that in aging rodent striatum. Comparisons of altered dopaminergic binding with other age-correlated changes suggest that neuronal loss may not be involved in the loss of binding sites before midlife.

Adolescent↗
PubMed1981

Catecholamine levels and turnover during aging in brain regions of male C57BL/6J mice.

A radioenzymatic assay is described for measuring brain catecholamines (CA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the same tissue extract. The [3H]-methylated products are differentially extracted and then acetylated by acetic anhydride, followed by thin layer chromatography in non-basic solvents. Routine sensitivity is 3-5 pg per sample. This assay gave CA levels in brain regions which generally agreed with previous reports. CA levels/mg protein and turnover (after injection of a-methyl-p-tyrosine) were measured in male C57BL/6J mice at various ages between 4 and 30 months, the average lifespan of male C57BL/6J mice. No region showed progressive age changes in levels or turnover, or changes before midlife, 8-12 months. Brain regions with no evidence of age changes include globus pallidus, zona incerta, substantia nigra, cerebellum, and olfactory bulbs. Small changes (10-25%) were detected in only some regions of mice aged greater than or equal to 24 months; few changes were statistically significant. CA levels and turnover decreased in some samplings of striatum and median eminence-arcuate nucleus. In contrast, DA levels increased in anterior pituitary and possibly in medial preoptic region. DOPAC levels (measured only in rostral striatum) decreased by 20% at 28 months. These results diverge from the larger, progressive decreases of DA reported in human striatum during aging.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Genotypic influences on striatal dopaminergic regulation in mice.

Genotypic influences on dopaminergic-induced behaviors and striatal dopaminergic receptors were evaluated in CBA/J, C57BL/6J and BALB/cJ male mice. CBA/J mice were less behaviorally sensitive to apomorphine (stereotypic behavior) but more sensitive to haloperidol (catalepsy) than C57BL/6J and BALB/cJ mice. Striatal dopaminergic receptors, assayed by binding of [3H]spiroperidol (antagonist) and [3H]ADTN (agonist), were 50% fewer in CBA/J compared to BALB/cJ mice; C57BL/6J mice had low to intermediate numbers of receptors. Striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations were similar in all strains. However, a 20% higher DOPAC/dopamine ratio in CBA/J mice suggests greater dopamine turnover. Median eminence dopamine was similar in all strains, but norepinephrine was 30% higher in BALB/cJ mice. CBA/J mice failed to show antagonist-induced supersensitivity-type responses to chronic haloperidol treatment: enhanced stereotypic response to apomorphine and a 30% increase of dopaminergic receptors occurred in C57BL/6J and BALB/cJ mice, but not in CBA/J mice. These data suggest that CBA/J mice either cannot respond to chronic haloperidol treatment or have an elevated threshold for induction of supersensitivity response. Chronic treatment with the dopamine agonist bromocriptine (7d) depressed apomorphine-induced stereotypic behavior in C57BL/6J mice and eliminated stereotypy in BALB/cJ mice, but caused no change in stereotypic behavior in CBA/J mice. Dopaminergic receptors were 15% lower after bromocriptine treatment in all strains. These results suggest that some striatal dopaminergic functions are impaired in CBA/J mice relative to BALB/cJ and C57BL/6J mice. The impaired haloperidol-induced supersensitivity responses in the CBA/J mouse may be a useful model for analyzing similar impairments of supersensitivity responses in old rodents.

Animals↗
PubMed1981

Pituitary tumorigenesis in aging female C57BL/6J mice: a light and electron microscopic study.

Spontaneous pituitary tumors have been studied by light and electron microscopy in female C57BL/6J mice at 2 1/2, 11, 15, 22, 23, 24 and 30 months. Tumors were evident macroscopically in greater than 50% of mice 22 months or older, and greater than 80% on microscopic evaluation. Active and hypertrophied mammotrophs were the predominant cell type within the tumors at 22-30 months, often totally filling large portions of the tumor mass. Exocytosis of secretory granules was extensive from the mammotrophs, but much less abundant from other parenchymal cells. Somatotrophs and gonadotrophs were also present, and appeared active and often strikingly hypertrophied. The tumors were characterized by disruptions of parenchymal and capillary integrity which resulted in the formation of large vascular lakes lined solely by tumor cells, generally mammotrophs. Apparent metastasis of tumor cells into the vascular lakes was also observed. In 11- and 15-month mice small tumors or pretumor foci were evident in some mice on microscopic evaluation, although they were not visible macroscopically. Their degree of development was somewhat variable, but they had essentially the same features as more advanced tumors in older mice. pretumor foci were characterized by more moderate disruptions of parenchymal cell and capillary integrity; cellular hypertrophy, particularly of somatotrophs and gonadotrophs; and the presence of small vascular lakes. In 2 1/2-month mice tumors could not be localized macroscopically or microscopically, and the pituitary was composed of well-defined cell cords and an intact capillary bed. However, small focal zones of capillary and tissue disruption were apparent occasionally in 2 1/2-month mice. These findings indicate that the process of pituitary tumorigenesis in female C57BL/6J mice is initiated by midlife, with subsequent progressive development into large, mammotroph-dominated tumors.

Aging↗
PubMed1981

Aging and haloperidol-induced dopamine turnover in the nigro-striatal pathway of C57BL/6J mice.

The responsiveness of male C57BL/6J mice to acute haloperidol (2.5 mg/kg, IP) was studied throughout the average adult lifespan (4, 8, 12, 21, 28 months) by effects on dopamine (DA) turnover, as estimated by DA loss after alpha-methyl-p-tyrosine (AMPT). Previously, striatal receptors for spiroperidol (a related butyrophenone) decreased progressively after 3 months to a loss of 40% by 28 months [29]. Haloperidol treatment (2 hours) accelerated striatal DA turnover similarly in all age groups, by about 100%. The haloperidol-induced accumulation of 3,4-dihydroxyphenylacetic acid (DOPAC) was not significantly impaired in AMPT treated mice with age. These results suggest that the age-related loss of butyrophenone binding sites may not limit acute compensatory responses to blockade of the remaining sites by a large dose of haloperidol. Regional differences in DA metabolism were detected between the substantia nigra (cell bodies and dendrites) and striatum (axonal terminals). Dopamine turnover and DOPAC levels were less in striatum than in substantia nigra; each region had a characteristic DOPAC/DA ratio (nigra, 38%; striatum, 7%); and, DOPAC levels did not precisely covary with DA turnover between regions. The constancy of DOPAC/DA ratios in controls and after AMPT treatment, in all ages suggests that a constant fraction of DA continued to be released and catabolized to DOPAC despite major decrease of DA after blockade of synthesis of DA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Aging and the regulation of striatal dopaminergic mechanisms in mice.

Compensatory responses of striatal dopaminergic mechanisms to chronic drug treatment were tested in C57BL/6J and C57BL/6NNia male mice during the adult lifespan (5, 12, and 24 to 26 months). Chronic treatment with haloperidol (dopamine antagonist) (1.2 or 2 mg/kg/day for 21 days) induced supersensitivity in younger mice (5 and 12 months) as monitored by increased striatal spiroperidol binding sites and increased intensity of apomorphine-induced stereotyped behavior; in contrast, old mice were unaffected. However, chronic treatment with bromocriptine (dopamine agonist) (15 mg/kg/day for 7 days) induced desensitization at all ages, as monitored by reduced spiroperidol binding sites and reduced intensity of stereotyped behavior.

Aging↗