Effects of whole-body vibration on reproductive physiology in a rat model of whole-body vibration.

Findings from epidemiological studies suggest that occupational exposure to whole-body vibration (WBV) may increase the risk of miscarriage and contribute to a reduction in fertility rates in both men and women. However, workers exposed to WBV may also be exposed to other risk factors that contribute to reproductive dysfunction. The goal of this experiment was to examine the effects of WBV on reproductive physiology in a rat model. Male and female rats were exposed to WBV at the resonant frequency of the torso (31.5 Hz, 0.3 g amplitude) for 4 hr/day for 10 days. WBV exposure resulted in a significant reduction in number of developing follicles, and decrease in circulating estradiol concentrations, ovarian luteinizing hormone receptor protein levels, and marked changes in transcript levels for several factors involved in follicular development, cell cycle, and steroidogenesis. In males, WBV resulted in a significant reduction in spermatids and circulating prolactin levels, elevation in number of males having higher circulating testosterone concentrations, and marked alterations in levels of transcripts associated with oxidative stress, inflammation, and factors involved in regulating the cell cycle. Based upon these findings data indicate that occupational exposure to WBV contributes to adverse alterations in reproductive physiology in both genders that may lead to reduction in fertility.

Exposure to graphene nanoparticles induces changes in measures of vascular/renal function in a load and form-dependent manner in mice.

Graphenes isolated from crystalline graphite are used in several industries. Employees working in the production of graphenes may be at risk of developing respiratory problems attributed to inhalation or contact with particulate matter (PM). However, graphene nanoparticles might also enter the circulation and accumulate in other organs. The aim of this study was to examine how different forms of graphene affect peripheral vascular functions, generation of reactive oxygen species (ROS) and changes in gene expression that may be indicative of cardiovascular and/or renal dysfunction. In the first investigation, different doses of graphene nanoplatelets were administered to mice via oropharyngeal aspiration. These effects were compared to those of dispersion medium (DM) and carbon black (CB). Gene expression alterations were observed in the heart for CB and graphene; however, only CB produced changes in peripheral vascular function. In the second study, oxidized forms of graphene were administered. Both oxidized forms increased the sensitivity of peripheral blood vessels to adrenoreceptor-mediated vasoconstriction and induced changes in ROS levels in the heart. Based upon the results of these investigations, exposure to graphene nanoparticles produced physiological and alterations in ROS and gene expression that may lead to cardiovascular dysfunction. Evidence indicates that the effects of these particles may be dependent upon dose and graphene form to which an individual may be exposed to.

Acute Vibration Induces Peripheral Nerve Sensitization in a Rat Tail Model: Possible Role of Oxidative Stress and Inflammation.

Prolonged occupational exposure to hand-held vibrating tools leads to pain and reductions in tactile sensitivity, grip strength and manual dexterity. The goal of the current study was to use a rat-tail vibration model to determine how vibration frequency influences factors related to nerve injury and dysfunction. Rats were exposed to restraint, or restraint plus tail vibration at 62.5 Hz or 250 Hz. Nerve function was assessed using the current perception threshold (CPT) test. Exposure to vibration at 62.5 and 250 Hz, resulted in a reduction in the CPT at 2000 and 250-Hz electrical stimulation (i.e. increased Aß and Aδ, nerve fiber sensitivity). Vibration exposure at 250 Hz also resulted in an increased sensitivity of C-fibers to electrical stimulation and thermal nociception. These changes in nerve fiber sensitivity were associated with increased expression of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in ventral tail nerves, and increases in circulating concentrations of IL-1 ß in rats exposed to 250-Hz vibration. There was an increase in glutathione, but no changes in other measures of oxidative activity in the peripheral nerve. However, measures of oxidative stress were increased in the dorsal root ganglia (DRG). These changes in pro-inflammatory factors and markers of oxidative stress in the peripheral nerve and DRG were associated with inflammation, and reductions in myelin basic protein and post-synaptic density protein (PSD)-95 gene expression, suggesting that vibration-induced changes in sensory function may be the result of changes at the exposed nerve, the DRG and/or the spinal cord.

Effects of pulmonary exposure to chemically-distinct welding fumes on neuroendocrine markers of toxicity.

Exposure to welding fumes may result in disorders of the pulmonary, cardiovascular, and reproductive systems. Welders are also at a greater risk of developing symptoms similar to those seen in individuals with idiopathic Parkinson's disease. In welders, there are studies that suggest that alterations in circulating prolactin concentrations may be indicative of injury to the dopamine (DA) neurons in the substantia nigra. The goal of these studies was to use an established model of welding particulate exposure to mimic the effects of welding fume inhalation on reproductive functions. Since previous investigators suggested that changes in circulating prolactin may be an early marker of DA neuron injury, movement disorders, and reproductive dysfunction, prolactin, hypothalamic tyrosine hydroxylase (TH) levels (a marker of DA synthesis), and other measures of hypothalamic-pituitary-gonadal (HPG) function were measured after repetitive instillation of welding fume particulates generated by flux core arc-hard surfacing (FCA-HS), manual metal arc-hard surfacing (MMA-HS) or gas metal arc-mild steel (GMA-MS) welding, or manganese chloride (MnCl2). Exposure to welding fume particulate resulted in the accumulation of various metals in the pituitary and testes of rats, along with changes in hypothalamic TH and serum prolactin levels. Exposure to particulates with high concentrations of soluble manganese (Mn) appeared to exert the greatest influence on TH activity levels and serum prolactin concentrations. Thus, circulating prolactin levels may serve as a biomarker for welding fume/Mn-induced neurotoxicity. Other reproductive measures were collected, and these data were consistent with epidemiological findings that prolactin and testosterone may serve as biomarkers of welding particulate induced DA neuron and reproductive dysfunction.

Factors affecting finger and hand pain in workers with HAVS.

BACKGROUND: Pain and its management are important aspects of hand-arm vibration syndrome (HAVS). AIMS: To determine the factors associated with finger and hand pain in workers with HAVS and, specifically, to assess the impact of several neurological variables as well as the vascular component of HAVS, grip strength and age. METHODS: We assessed men with HAVS at a hospital occupational medicine clinic over 2 years. Subjects scored finger and hand pain separately using the Borg Scale (0-10). The possible predictors we evaluated included the Stockholm Neurological Scale (SNS) and Stockholm Vascular Scale (SVS) stages, current perception threshold (CPT), carpal tunnel syndrome (CTS), ulnar neuropathy, grip strength and age. We carried out nerve conduction testing to confirm the presence of CTS and ulnar neuropathy and measured CPT in the fingers at 2000 Hz, 250 Hz and 5 Hz corresponding to A-beta (large myelinated), A-delta (small myelinated) and C (unmyelinated) fibres, respectively. We calculated Spearman rank correlations to examine the relation between finger and hand pain and possible predictor variables. RESULTS: Among the 134 subjects, the median (25th-75th percentile) pain scores were 6 (4-8) for the fingers and 5 (1-7) for the hands. We found statistically significant correlations with finger pain for the SVS stage (r = 0.239; P < 0.01) and CTS (r = 0.184; P < 0.05). The only statistically significant correlation identified for hand pain was a negative correlation with grip strength (r = -0.185; P < 0.05). CONCLUSIONS: Management of finger and hand pain in HAVS should focus on the correlates we have identified.

Changes in the expression of calcitonin gene-related peptide after exposure to injurious stretch-shortening contractions.

UNLABELLED: One of the factors that can result in musculoskeletal injuries, and time off work, is exposure to repetitive motion. The goal of this study was to determine if skeletal muscle injury induced by exposure to injurious stretch-shortening cycles (iSSCs), resulted in hyperalgesia in the hind limb and changes in calcitonin-gene related peptide (CGRP) immunolabeling in the dorsal root ganglia (DRG) in young and old male rats. METHODS: Young (3months) and old (30months) male Fisher 344×BN F1 rats were anesthetized with isoflurane and the left hind limbs were exposed to 15 sets of 10 SSCs. Control animals were exposed to a single bout of SSCs of equal intensity. Sensitivity to mechanical stimulation was assessed using von Frey filaments prior to beginning the experiment, and on days 2 and 9 following exposure to iSSCs. Rats were euthanized one, 3 or 10days after the exposure. The ipsilateral DRG were dissected from the L4-5 region of the spine, along with the left tibialis anterior (LTA) muscle. RESULTS: Rats exposed to iSSCs were more sensitive to mechanical stimulation than control rats 2days after the exposure, and showed a reduction in peak force 3days after exposure. Changes in sensitivity to pressure were not associated with increases in CGRP labeling in the DRG at 3days. However, 9days after exposure to iSSCs, old rats still displayed an increased sensitivity to mechanical stimulation, and this hyperalgesia was associated with an increase in CGRP immunolabeling in the DRG. Young rats exposed to iSSC did not display a change in CGRP immunolabeling and sensitivity to mechanical stimulation returned to control levels at 10days. CONCLUSIONS: These findings suggest that hyperalgesia seen shortly after exposure to iSSC is not influenced by CGRP levels. However, in cases where recovery from injury may be slower, as it is in older rats, CGRP may contribute to the maintenance of hyperalgesia.

Antivibration gloves: effects on vascular and sensorineural function, an animal model.

Anti-vibration gloves have been used to block the transmission of vibration from powered hand tools to the user, and to protect users from the negative health consequences associated with exposure to vibration. However, there are conflicting reports as to the efficacy of gloves in protecting workers. The goal of this study was to use a characterized animal model of vibration-induced peripheral vascular and nerve injury to determine whether antivibration materials reduced or inhibited the effects of vibration on these physiological symptoms. Rats were exposed to 4 h of tail vibration at 125 Hz with an acceleration 49 m/s(2). The platform was either bare or covered with antivibrating glove material. Rats were tested for tactile sensitivity to applied pressure before and after vibration exposure. One day following the exposure, ventral tail arteries were assessed for sensitivity to vasodilating and vasoconstricting factors and nerves were examined histologically for early indicators of edema and inflammation. Ventral tail artery responses to an α2C-adrenoreceptor agonist were enhanced in arteries from vibration-exposed rats compared to controls, regardless of whether antivibration materials were used or not. Rats exposed to vibration were also less sensitive to pressure after exposure. These findings are consistent with experimental findings in humans suggesting that antivibration gloves may not provide protection against the adverse health consequences of vibration exposure in all conditions. Additional studies need to be done examining newer antivibration materials.

Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles.

Our laboratory has previously demonstrated that application of an antimicrobial spray product containing titanium dioxide (TiO(2)) generates an aerosol of titanium dioxide in the breathing zone of the applicator. The present report describes the design of an automated spray system and the characterization of the aerosol delivered to a whole body inhalation chamber. This system produced stable airborne levels of TiO(2) particles with a median count size diameter of 110 nm. Rats were exposed to 314 mg/m(3) min (low dose), 826 mg/m(3) min (medium dose), and 3638 mg/m(3) min (high dose) of TiO(2) under the following conditions: 2.62 mg/m(3) for 2 h, 1.72 mg/m(3) 4 h/day for 2 days, and 3.79 mg/m(3) 4 h/day for 4 days, respectively. Pulmonary (breathing rate, specific airway resistance, inflammation, and lung damage) and cardiovascular (the responsiveness of the tail artery to constrictor or dilatory agents) endpoints were monitored 24 h post-exposure. No significant pulmonary or cardiovascular changes were noted at low and middle dose levels. However, the high dose caused significant increases in breathing rate, pulmonary inflammation, and lung cell injury. Results suggest that occasional consumer use of this antimicrobial spray product should not be a hazard. However, extended exposure of workers routinely applying this product to surfaces should be avoided. During application, care should be taken to minimize exposure by working under well ventilated conditions and by employing respiratory protection as needed. It would be prudent to avoid exposure to children or those with pre-existing respiratory disease.

Vasospasm in the feet in workers assessed for HAVS.

BACKGROUND: Previous studies have suggested that the presence of the vascular component of hand-arm vibration syndrome (HAVS) in the hands increases the risk of cold-induced vasospasm in the feet. AIMS: To determine if objectively measured cold-induced vasospasm in the hands is a risk factor for objectively measured cold-induced vasospasm in the feet in workers being assessed for HAVS. METHODS: The subjects were 191 male construction workers who had a standardized assessment for HAVS including cold provocation digital photocell plethysmography of the hands and feet to measure cold-induced vasospasm. Bivariate analysis and multinomial logistic regression were used to examine the association between plethysmographic findings in the feet and predictor variables including years worked in construction, occupation, current smoking, cold intolerance in the feet, the Stockholm vascular stage and plethysmographic findings in the hands. RESULTS: Sixty-one (32%) subjects had non-severe vasospasm and 59 (31%) had severe vasospasm in the right foot with the corresponding values being 57(30%) and 62 (32%) in the left foot. Multinomial logistic regression indicated that the only statistically significant predictor of severe vasospasm in the feet was the presence of severe vasospasm in the hands (OR: 4.11, 95% CI: 1.60-10.6, P < 0.01 on the right side and OR: 4.97, 95% CI: 1.82-13.53, P < 0.01 on the left side). Multinomial logistic regression analysis did not indicate any statistically significant predictors of non-severe vasospasm in the feet. CONCLUSIONS: Workers assessed for HAVS frequently have cold-induced vasospasm of their feet. The main predictor of severe vasospastic foot abnormalities is severe cold-induced vasospasm in the hands.

Vibration-white foot: a case report.

BACKGROUND: Hand-arm vibration syndrome (HAVS) refers to the neurological, vascular and musculoskeletal problems that may arise due to exposure to segmental vibration to the hands. An analogous syndrome may occur in the lower extremities of workers exposed to foot-transmitted vibration. AIMS: This report describes the case of a worker with a history of foot-transmitted vibration exposure presenting with cold intolerance in the feet and blanching in the toes. Case report A 54-year-old miner presented with a chief complaint of blanching and pain in his toes. The worker had a history of foot-transmitted vibration exposure over his 18 year career as a miner, primarily from the operation of vehicle-mounted bolting machines. Cold provocation digital plethysmography showed cold-induced vasospastic disease in the feet, but not in the hands. CONCLUSIONS: This case illustrates a condition descriptively termed 'vibration-white foot': a disease analogous to HAVS arising after segmental vibration exposure to the feet. Further research is required to increase awareness of, and direct preventive efforts for, this potentially debilitating condition.

An investigation on the biodynamic foundation of a rat tail vibration model.

The objectives of this study are to examine the fundamental characteristics of the biodynamic responses of a rat tail to vibration and to compare them with those of human fingers. Vibration transmission through tails exposed to three vibration magnitudes (1 g, 5 g, and 10 g r.m.s.) at six frequencies (32 Hz, 63 Hz, 125 Hz, 160 Hz, 250 Hz, and 500 Hz) was measured using a laser vibrometer. A mechanical-equivalent model of the tail was established on the basis of the transmissibility data, which was used to estimate the biodynamic deformation and vibration power absorption at several representative locations on the tail. They were compared with those derived from a mechanical-equivalent model of human fingers reported in the literature. This study found that, similar to human fingers, the biodynamic responses of the rat tail depends on the vibration magnitude, frequency, and measurement location. With the restraint method used in this study, the natural frequency of the rat tail is in the range 161-368 Hz, which is mostly within the general range of human finger resonant frequencies (100-350 Hz). However, the damping ratios of the rat tail at the unconstrained locations are from 0.094 to 0.394, which are lower than those of human fingers (0.708-0.725). Whereas the biodynamic responses of human fingers at frequencies lower than 100 Hz could be significantly influenced by the biodynamics of the entire hand-arm system, the rat tail biodynamic responses can be considered independent of the rat body in the frequency range used in this study. Based on these findings it is concluded that, although there are some differences between the frequency dependences of the biodynamic responses of the rat tail and human fingers, the rat tail model can provide a practical and reasonable approach to examine the relationships between the biodynamic and biological responses at midrange to high frequencies, and to understand the mechanisms underlying vibration-induced finger disorders.

Acute vibration increases alpha2C-adrenergic smooth muscle constriction and alters thermosensitivity of cutaneous arteries.

The vascular symptoms of hand-arm vibration syndrome, including cold-induced vasospasm, are in part mediated by increased sensitivity of cutaneous arteries to sympathetic stimulation. The goal of the present study was to use a rat tail model to analyze the effects of vibration on vascular function and alpha-adrenoceptor (AR) responsiveness. Rats were exposed to a single period of vibration (4 h, 125 Hz, constant acceleration 49 m/s2 root mean square). The physical or biodynamic response of the tail demonstrated increased transmissibility or resonance at this frequency, similar to that observed during vibration of human fingers. Morphological analysis demonstrated that vibration did not appear to cause structural injury to vascular cells. In vitro analysis of vascular function demonstrated that constriction to the alpha1-AR agonist phenylephrine was similar in vibrated and control arteries. In contrast, constriction to the alpha2-AR agonist UK14304 was increased in vibrated compared with control arteries, both in endothelium-containing or endothelium-denuded arteries. The alpha2C-AR antagonist MK912 (3 x 10(-10) M) inhibited constriction to UK14304 in vibrated but not control arteries, reversing the vibration-induced increase in alpha2-AR activity. Moderate cooling (to 28 degrees C) increased constriction to the alpha2-AR agonist in control and vibrated arteries, but the magnitude of the amplification was less in vibrated compared with control arteries. Endothelium-dependent relaxation to acetylcholine was similar in control and vibrated arteries. Based on these results, we conclude that a single exposure to vibration caused a persistent increase in alpha2C-AR-mediated vasoconstriction, which may contribute to the pathogenesis of vibration-induced vascular disease.

Analysis of the dynamic strains in a fingertip exposed to vibrations: Correlation to the mechanical stimuli on mechanoreceptors.

The reduction in vibrotactile sensitivity in the fingertip is assumed to be associated with the exposure of the tissues to repetitive, non-physiological strains during dynamic loading. Experimental results demonstrated that the magnitude of a vibration-induced temporary threshold shift is dependent upon the vibration frequency of both the exposure and testing stimuli. In the present study, the frequency-dependent strain imposed on cutaneous and subcutaneous tissues of the fingertip is analyzed theoretically using a finite element model. The proposed fingertip model is two-dimensional and includes major anatomical substructures: skin, subcutaneous tissue, bone, and nail. The soft tissues (skin and subcutaneous tissues) were assumed to be nonlinearly elastic and viscoelastic, while the bone and nail were considered as linearly elastic. Simulations were performed for the contact between the fingertip and a flat surface for four different pre-compressions (0.5, 1.0, 1.5, and 2.0 mm). The frequency-dependent distributions of the dynamic strain magnitudes in the soft tissues were investigated. The model predictions indicated that the vibration exposure at a frequency range from 63 to 250 Hz will induce excessive dynamic strain in the deep zone of the finger tissues, effectively inhibiting the high-frequency mechanoreceptors; while the vibration exposure at low frequency (less than 31.5 Hz) tends to induce excessive dynamic strain in superficial layer in the tissues, inhibiting the low-frequency mechanoreceptors. These theoretical predictions are consistent with the experimental observations in literature. The proposed model can be used to predict the responses of the soft tissues in different depths to vibration exposures, providing valuable information and data that are essential for improving vibrotactile perception tests.

Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea pigs.

This study tests the hypothesis that the bronchial hyperreactivity induced by chronic cigarette smoke (CS) exposure involves the increased expression and release of tachykinins and calcitonin gene-related peptide (CGRP) from afferent nerve fibers innervating the airways. In guinea pigs chronically exposed to CS (20 min twice daily for 14-17 d), peak response in total lung resistance to capsaicin (1.68 microg/kg, intravenously) was significantly greater than that evoked by the same dose of capsaicin in control (air-exposed) animals. This augmented response in CS-exposed animals was abolished after treatment with CP-99994 and SR-48968, the neurokinin (NK)-1 and NK-2 receptor antagonists, suggesting the involvement of tachykinins in chronic CS-induced airway hyperresponsiveness (AHR). Further, substance P (SP)-like immunoreactivity (LI) and CGRP-LI in the airway tissue were significantly greater in the CS animals than in the control animals. Finally, beta-preprotachykinin (PPT, a splice variant from the PPT A gene encoding tachykinins including SP and NKA) messenger RNA levels as measured by in situ hybridization histochemistry displayed a significant increase in jugular ganglion neurons but not in dorsal root or nodose ganglion neurons. These data suggest that chronic CS-induced AHR is related to an increase in SP synthesis and release in jugular ganglion neurons innervating the lungs and airways.

Fos-induction in gonadotropin-releasing hormone neurons receiving vasoactive intestinal polypeptide innervation is reduced in middle-aged female rats.

A hallmark of reproductive aging in rats is a delay in the initiation and peak, and a decrease in the amplitude, of both proestrous and steroid-induced surges of LH and a decrease in the number of GnRH neurons that express Fos during the surge. The altered timing of the LH surge and the decline in Fos expression in GnRH neurons may be due to changes in the rhythmic expression of vasoactive intestinal polypeptide (VIP), a neuropeptide that carries time-of-day information from the circadian pacemaker, located in the suprachiasmatic nuclei (SCN), to GnRH neurons. The goals of our study were to determine if aging alters 1) the innervation of GnRH neurons by VIP and 2) the ability of VIP to activate GnRH neurons by examining the effects of aging on the number of GnRH neurons apposed by VIP fibers and the number of GnRH neurons that receive VIP input that express Fos. Immunocytochemistry for GnRH and VIP; or GnRH, VIP, and Fos was performed on tissue sections collected from young (2-4 mo), regularly cycling females and middle-aged (10-12 mo) females in constant estrus. The number of GnRH neurons, GnRH neurons apposed by VIP fibers, and GnRH neurons that express Fos and apposed by VIP fibers were counted in both age groups. Our results clearly demonstrate that aging does not alter the number of GnRH neurons that receive VIP innervation. However, the number of GnRH neurons that receive VIP innervation and coexpress Fos decreases significantly. We conclude that the age-related delay in the timing of the LH surge is not due to a change in VIP innervation of GnRH neurons, but instead may result from a decreased sensitivity of GnRH neurons to VIP input.

Neuroendocrine influences and repercussions of the menopause.

In summary, the evidence that both the ovary and the brain are key pacemakers in the menopause is compelling. Our appreciation that estrogens are important neurotrophic and neuroprotective factors has grown rapidly. Future studies will allow us to better understand the ensemble of factors that interact to maintain regular reproductive cyclicity and how this precise dynamic balance changes with age. Furthermore, understanding how estrogen exerts trophic and protective actions should lead to its use as an important therapeutic agent in the maintenance of normal neural function during aging and after injury.

Sex differences in the daily rhythm of vasoactive intestinal polypeptide but not arginine vasopressin messenger ribonucleic acid in the suprachiasmatic nuclei.

The timing of the preovulatory surge of LH in female rodents is tightly coupled to the environmental light/dark cycle. This coupling is mediated by the circadian pacemaker located in the suprachiasmatic nuclei (SCN). Studies indicate that vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP), which are synthesized in the SCN, transmit circadian information from the SCN to GnRH neurons, thereby regulating the timing of the LH surge. However, to date, the rhythmic expression of these two peptides in the SCN has only been examined in males. The pattern of VIP expression in males is difficult to reconcile with its role in the LH surge. The purpose of the present study was to assess the rhythm of VIP messenger RNA (mRNA) levels in the SCN of female rats under several endocrine conditions. We compared this rhythm to that in males and to AVP mRNA rhythms in all experimental groups. In all groups of females, VIP mRNA levels were rhythmic, with peak expression occurring during the light phase and a nadir occurring during the dark phase. The rhythm was approximately 12 h out of phase compared with that in males. The rhythmic expression of AVP mRNA in the SCN was virtually identical in all groups of animals. Based on these results, we conclude that 1) the rhythm of VIP seen in the SCN of females during the day may serve as a facilitory signal from the SCN to GnRH neurons; 2) the sex-specific pattern of VIP mRNA does not depend on estradiol; and 3) AVP gene expression within the SCN is not sexually differentiated or altered by estradiol.

Aging alters the rhythmic expression of vasoactive intestinal polypeptide mRNA but not arginine vasopressin mRNA in the suprachiasmatic nuclei of female rats.

Our laboratory has shown that the ability of the suprachiasmatic nuclei (SCN) to regulate a number of rhythmic processes may be compromised by the time females reach middle age. Therefore, we examined the effects of aging on the rhythmic expression of two neuropeptides synthesized in the SCN, vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP), using in situ hybridization. Because both VIP and AVP are outputs of the SCN, we hypothesized that age-related changes in rhythmicity are associated with alterations in the patterns of expression of these peptides. We found that VIP mRNA levels exhibited a 24 hr rhythm in young females, but by the time animals were middle-aged, this rhythm was gone. The attenuation of rhythmicity was associated with a decline in the level of mRNA per cell and in the number of cells in the SCN producing detectable VIP mRNA. AVP mRNA also showed a robust 24 hr rhythm in young females. However, in contrast to VIP, the AVP rhythm was not altered in the aging animals. The amount of mRNA per cell and the number of cells expressing AVP mRNA also was not affected with age. Based on these results we conclude that (1) various components of the SCN are differentially affected by aging; and (2) age-related changes in various rhythms may be attributable to changes in the ability of the SCN to transmit timing information to target sites. This may explain why the deterioration of various rhythmic processes occurs at different rates and at different times during the aging process.

The induction of Fos-like proteins in the suprachiasmatic nuclei and intergeniculate leaflet by light pulses in degus (Octodon degus) and rats.

In nocturnal rodents, exposure to light results in an increase in Fos expression in two regions that receive direct retinal input: the suprachiasmatic nuclei (SCN) of the hypothalamus and the intergeniculate leaflet (IGL) of the thalamus. The induction of Fos within the SCN of nocturnal rodents is phase dependent, with light presented during the subjective night increasing Fos expression and light presented during the subjective day having little effect. By contrast, Fos expression increases in the IGL when light is presented during the subjective day or night. It is unclear whether Fos is part of the pathway mediating light-induced phase shifts in diurnal rodents. In the present study, the ability of light to induce immunostaining for Fos in the SCN and IGL was compared in diurnal rodents, Octodon degus (degus), and nocturnal rats. Degus and rats were either maintained in constant darkness or exposed to a 1-h light pulse at circadian time (CT) 4 or 16. Degus exhibit robust phase shifts at each of those circadian hours, whereas rats demonstrate phase shifts only at CT 16. In degus, exposure to a 1-h light pulse at CT 16 resulted in an increase in the number of Fos-immunopositive (Fos+) cells in the ventrolateral SCN. By contrast, a 1-h light pulse at CT 4 resulted in a decrease in the number of Fos+ cells in the dorsomedial portion of the SCN. In rats, a light pulse presented at CT 16 resulted in an increase in Fos+ cells throughout the SCN, and a pulse at CT 4 had no effect on Fos staining. Both degus and rats showed increases in Fos expression in the IGL after light exposure at CTs 4 and 16. The authors conclude that light pulses presented at times that produce phase shifts in activity rhythms also alter Fos expression in the SCN and IGL of degus. Although these effects of light exposure on Fos expression are not identical in diurnal and nocturnal rodents, it is likely that Fos and other immediate early genes are part of the pathway mediating the effects of light in both diurnal and nocturnal rodents.

Aging of the female reproductive system: a window into brain aging.

The menopause marks the permanent end of fertility in women. It was once thought that the exhaustion of ovarian follicles was the single, most important explanation for the transition to the menopause. Over the past decade, this perception has gradually changed with the realization that there are multiple pacemakers of reproductive senescence. We will present evidence that lends credence to the hypothesis that the central nervous system is a critical pacemaker of reproductive aging and that changes at this level contribute to the timing of the menopause. Studies demonstrate that an increasing de-synchronization of the temporal order of neuroendocrine signals may contribute to the accelerated rate of follicular loss that occurs during middle age. We suggest that the dampening and destabilization of the precisely orchestrated ultradian, circadian, and infradian neural signals lead to miscommunication between the brain and the pituitary-ovarian axis. This constellation of hypothalamic-pituitary-ovarian events leads to the inexorable decline of regular cyclicity and heralds menopausal transition.