Physiology of the young adult Fischer 344 rat inferior colliculus: responses to contralateral monaural stimuli

This study was designed to establish the young adult (3 month) Fischer 344 (F344) rat as a model of inferior colliculus (IC) physiology, providing a baseline for analysis of changes in single unit responses as the animals age and for the study of noise induced hearing loss. The response properties of units localized to the central nucleus of the IC (CIC) and those localized to the external cortex of the IC (ECIC) were compared in order to better characterize differences between these two subnuclei in the processing of simple auditory stimuli. In vivo extracellular single unit recordings were made from IC neurons in ketamine/xylazine anesthetized young adult F344 rats. When a unit was electrically isolated, the spontaneous activity level, characteristic frequency (CF) and CF threshold were determined. Rate/intensity functions (RIFs) in response to contralateral CF tones and to contralateral noise bursts were obtained as were tone isointensity functions. The recording site was marked by ejecting horseradish peroxidase (HRP) from an electrode. Locations of recorded units were determined from electrode track marks and HRP marks in serial brain sections. Recordings were made from 320 neurons in the IC; 176 were localized to the CIC and 87 to the ECIC. Thirteen percent of the units in each subdivision were found to be poorly responsive to auditory stimulation (clicks, tones or noise), and spontaneous activity was generally low. Characteristic frequencies representative of the full rat audiogram were found in each subdivision with the mean threshold significantly higher in the ECIC (28.7 dB SPL) than in the CIC (22.3 dB SPL). The mean maximum discharge rate to CF tone bursts was near 24 spikes/s in each subdivision. Dynamic range tended to be higher in the ECIC (28.3 dB) than in the CIC (23.2 dB), reflecting the lower percentage of nonmonotonic units found in the ECIC. Most units responded more robustly with a slower tone presentation rate, displayed lower levels of discharge to noise bursts than to tone bursts, and had differently shaped tone and noise RIFs. Most units were classified as onset responders to CF tone bursts in both subdivisions, with the percentage of onset responders higher in the ECIC (68.9%) than in the CIC (57.8%). First spike latency did not differ significantly between the subdivisions, but tended to be shorter in the CIC. The breadth of the excitatory receptive fields did not differ significantly between subdivisions, although the mean was slightly larger in the ECIC. These results are generally consistent with the results of CIC studies from other species, establishing the F344 rat as a model of CIC physiology. Differences between CIC and ECIC units included a higher percentage of nonmonotonic RIFs and lower percentage of onset temporal response patterns in the CIC than in the ECIC. Some properties which have been previously used as hallmarks for differentiation between CIC and ECIC units, namely broader tuning and longer first spike latencies in the ECIC, did not reach statistical significance in this study. These may reflect species differences and/or the highly variable and largely overlapping sets of responses evident in the large sample size used in this study.     

Hereditary primary childhood glaucomas

Experimental autoimmune encephalomyelitis (EAE) was induced in young (2-3 month old), middle-aged (12-13 month old) and geriatric (24-26 month old) Lewis (JC) rats by active immunisation with myelin basic protein (MBP) in complete Freund's adjuvant (CFA). It was found that aged Lewis (JC) rats developed a more chronic form of EAE than younger rats of the same strain, a phenomenon observed in both male and female rats despite males developing more severe disease than females at all ages. Middle-aged recipients also developed more severe disease than young recipients when EAE was induced by the adoptive transfer of lymphocytes from actively immunised young donors, suggesting that disease chronicity in middle-aged animals is a property of the central nervous system (CNS) milieu. Histological studies demonstrated that disease chronicity did not correlate with the number of inflammatory lesions in the CNS, young animals containing substantial numbers of CNS lesions following recovery and lesions being largely absent from middle-aged animals which still exhibited signs of disease. No significant differences were found in the degree of fibrin deposition or demyelination between young and middle-aged or symptomatic and asymptomatic animals. However, astrocytic hypertrophy was found to correlate with manifestation of disease in both young and middle-aged animals and in particular with disease chronicity in middle-aged animals. In parallel studies, no significant differences were found in the levels of the inflammatory mediators tumor necrosis factor (TNF)-alpha, prostaglandin E (PGE)2, reactive nitrogen intermediates (RNI) and corticosterone in young and middle-aged animals. However, markedly elevated corticosterone levels were found in both young and middle-aged animals with the development of clinical signs which returned to baseline levels with the resolution of clinical signs. Elevated levels of RNI were evident in animals immediately prior to and during the early stages of symptomatic EAE. Although these results suggest that nitric oxide may play a role in the pathogenesis of disease, whereas corticosterone may play a role in the immunoregulation of the disease, these factors cannot explain differences in disease chronicity evident in middle-aged animals.(ABSTRACT TRUNCATED AT 400 WORDS)     

The beta adrenoreceptor antagonist, nipradilol, preserves the endothelial nitric oxide response in atherosclerotic vessels of rabbit

We evaluated the effects of nipradilol, a beta-adrenoreceptor antagonist which contains a nitroxy residue, for vascular response in atherosclerosis of rabbits. Four groups of rabbits received different diets (standard diet; standard diet plus 10 mg/kg/day nipradilol; atherogenic diet [standard diet plus 1% cholesterol]; atherogenic diet plus 10 mg/kg/day nipradilol) for 9 weeks. Plasma lipids, blood pressure, vascular function, nitric oxide (NO), activity of NO synthase, cGMP, and histological atherosclerotic changes were evaluated. Neither the atherogenic diet nor nipradilol treatment affected significantly the animals' body weight, blood pressure, or heart rate. The atherogenic diet increased total cholesterol and triglycerides, which were not altered by nipradilol. The atherogenic diet diminished the acetylcholine-induced NO mediated relaxation. Nipradilol treatment restored this relaxation. Analyses using a NO-sensitive selective electrode showed that nipradilol released NO in the presence of cells and that NO release was greater in atherosclerotic aorta with than without nipradilol treatment. Nipradilol treatment increased the basal NO release as evaluated by the aortic tissue cyclic GMP (cGMP) levels in atherosclerotic vessel, and reduced the esterified cholesterol levels in atherosclerotic vessel. Conclusively, NO released by nipradilol may protect endothelium derived relaxation in atherosclerotic vessels, and may partially inhibit the accumulation of cholesterol in the atherosclerotic lesions.     

Aggregation of a subpopulation of vimentin filaments in cultured human skin fibroblasts derived from patients with giant axonal neuropathy

We studied the effect of age and calorie restriction on the expression of genes involved in antioxidant defenses in livers of young (4.5-6 months) and old (22 months) Emory mice fed a control (C) or restricted (R) diet. Specifically examined were catalase (CAT), glutathione peroxidase (Gpx), Cu/Zn and Mn superoxide dismutase (Cu/ZnSOD and MnSOD). As an indicator of oxidative damage to the tissues we measured lipid peroxidation. As indicators of oxidative stress we determined ubiquitin mRNA levels and endogenous high molecular weight (HMW) ubiquitin conjugates. Lower mRNA levels of ubiquitin (P < 0.05), CAT (P < 0.01) and Gpx (P < 0.01) were observed in tissues from young R versus C animals. The old C group had a lower CAT mRNA level (P < 0.0001) compared with young C. In the R group, age did not affect the CAT mRNA levels or Gpx mRNA levels; however, ubiquitin mRNA levels were higher (P < 0.05). No significant changes in Cu/Zn or MnSOD mRNA were observed with age or diet. Cu/ZnSOD protein levels were lower in the young R at 4.5 months (P < 0.05) than young C, and higher in the old R group versus old C (P < 0.05). CAT protein levels were higher in the old C versus old R (P < 0.05). Changes of HMW ubiquitin conjugates with age r diet were not significant. Of the four groups, the old R group showed the highest levels of lipid peroxidation.     

Cerebrospinal fluid inositol monophosphatase: elevated activity in depression and neuroleptic-treated schizophrenia

In this study we assessed whether widely accepted risk factors for atherosclerotic vascular diseases such as lipoprotein(a) [Lp(a)], a cholesterol-rich lipoprotein under strict genetical control, and other lipid parameters change with age. The variations of blood levels and the pathophysiological role of Lp(a) in old people, and particularly in the oldest old, are unknown. Accordingly, we measured Lp(a) levels as well as total, LDL, and HDL cholesterol (CT), and triglycerides (TG) in sera from 75 healthy centenarians, 114 randomly selected subjects under 65 years, 73 randomly selected elderly people, and 30 healthy selected elderly people. The results showed that Lp(a) serum levels did not vary by age group, including centenarians. Remarkably, one-quarter of the centenarians had high Lp(a) serum levels even though they never suffered from atherosclerosis-related diseases. At variance with young and aged people, centenarians with high Lp(a) serum levels also had high plasma concentrations of the proinflammatory cytokine IL-6, suggesting that genetic control of the Lp(a) serum level may attenuate with age and that environmental factors such as chronic subclinical inflammatory processes may play a role. We also showed that most centenarians are paradoxically characterized by low HDL-CT and relatively high TG levels, which together are considered to be strong risk factors for coronary heart disease. On the whole, these data support the hypothesis that a continuous and complex reshaping of lipid metabolism occurs in physiological aging, likely contributing to successful aging.     

Adult-onset energy restriction of rhesus monkeys attenuates oxidative stress-induced cytokine expression by peripheral blood mononuclear cells

We previously reported that energy restriction (ER) of mice attenuated age-associated increases in serum levels of interleukin-6 (IL-6). Here, we studied peripheral blood mononuclear cells (PBMC) from male rhesus monkeys to investigate the following: 1) the production of IL-6 and other cytokines become dysregulated with aging; 2) ER influences cytokine production and mRNA expression; and, 3) oxidative stress, as induced in vitro by xanthine and xanthine oxidase (X/XOD), influences cytokine mRNA and protein levels. Two types of comparisons were made as follows: 1) between normally fed young (6-9 y) and old monkeys (22-33 y); and 2) between middle-aged monkeys (15-21 y) fed either a normal energy intake or subjected to ER (for 5.5 y at 30% less than base-line intake). IL-6 protein levels and X/XOD-induced IL-6 mRNA levels in PBMC from old monkeys were significantly greater than those in PBMC from young animals. In contrast, interleukin-1beta (IL-1beta) and interleukin-8 mRNA levels were not strongly influenced by advancing age. X/XOD, which increased levels of protein carbonyls (indicative of oxidative damage) in PBMC, induced the expression of all three cytokines. ER reduced IL-6 protein and mRNA levels induced by X/XOD and the unstimulated mRNA levels of IL-1beta. These results indicate that, in a nonhuman primate model, oxidative stress may contribute to age-associated increases in the levels of certain cytokines and that adult-onset ER partially ameliorates this alteration.     

Influence of biological factors on lipid and fibrinogen measurements in young men. An epidemiological study in 2009 recruits

AIMS: The aim of the present study was to detect significant relationships between lipid and fibrinogen measurements and several biological factors in young men. METHODS AND RESULTS: Medical history was obtained, and plasma lipids, lipoprotein (a) and fibrinogen levels were measured in 2009 male Greek army recruits (mean age 22.37+/-3.03 years) not taking any drugs. Plasma levels were as follows: total cholesterol, 171+/-34 mg x dl(-1), low density lipoprotein (LDL) cholesterol, 111+/-34 mg x dl(-1), high density lipoprotein (HDL) cholesterol, 45+/-10 mg x dl(1), and triglycerides, 74+/-32 mg x dl(-1). Lipoprotein (a) and fibrinogen were 18+/-13 and 278+/-67 mg x dl(-1). The atherosclerotic index, calculated as the ratio of total cholesterol/HDL, was 4+/-1. Analysis of multivariate models that included potentially confounding factors revealed the following: body mass index, season of year during which blood examinations were performed, alcohol consumption, and place of residence were found to be significantly associated with plasma levels of total cholesterol, LDL-cholesterol, fibrinogen and the atherosclerotic index in the pooled population. Season and physical activity were significantly associated with HDL-cholesterol, whereas season and family history of acute myocardial infarction were associated with triglycerides levels. Body mass index, family history of myocardial infarction and physical activity were associated with lipoprotein (a). CONCLUSION: Body mass index, season, alcohol consumption and place of residence are markers of plasma lipid profile and fibrinogen in young men. A family history of acute myocardial infarction and physical activity are related to lipoprotein (a).     

Watanabe rabbits with heritable hypercholesterolaemia: a model of atherosclerosis

Many factors play important roles in the development of atherosclerotic lesions. The leading risk factor for atherosclerosis is familial hypercholesterolaemia (FH). FH is a genetic disease characterized by a deficiency of receptors for low density lipoprotein (LDL) on the plasmalemma of endothelial cells, a high level of serum LDL, and early development of atherosclerosis and skin xanthoma. Watanabe and colleagues have developed a line of rabbits with unprovoked hypercholesterolaemia, increased blood level of LDL, pronounced atherosclerosis and skin xanthoma. These Watanabe Heritable Hyperlipidaemic (WHHL) rabbits possess an inheritable mutation of one gene, similar to that in human FH. The morphogenesis of atherosclerosis in patients with FH is characterized by multifocal deposit of lipids in the stromal cells of thymus, spleen, skin, interstitial and parenchymatous cells of kidneys and the presence of some single foam cells in aorta. The manifestation of atherosclerotic lesions in WHHL rabbits increases progressively with age but the presence of atherosclerotic lesions in newborn WHHL rabbits suggest that the process may commence in utero. Moreover, the main mass of plasma cholesterol in WHHL rabbits is first found in LDL and to a lesser degree in lipoproteins of intermediate density. This is contrary to diet-induced atherosclerosis in rabbits where the main mass of serum cholesterol is found in very low density beta-lipoproteins. Thus the distribution of cholesterol among lipoprotein fractions differs from that in WHHL rabbits. Atherosclerotic damage of arteries in WHHL rabbits goes through several stages. During the progression of intimal damage, lipid and foam cell deposits are found in the internal surface together with developing plaques and increased content of lipids in the tunica media. Calcification often follows this process. The main factors initiating atherosclerosis in WHHL rabbits are adhesion of leukocytes and platelets to endothelial cells and the accumulation of lipids in the aortic wall. The deposits of lipids in macrophages and intimal smooth muscle cells in WHHL rabbits occurs mostly at the expense of cytoplasmic neutral lipid particles with some accumulation in lysosomes. Hypertension as a risk factor increases the area of atherosclerotic damage in all arterial vessels in WHHL rabbits, particularly in the thoracic and abdominal aorta. Morphogenesis of the development of atherosclerosis in WHHL and diet-induced atherosclerosis in rabbits was similar, but differs from rats with heritable hypercholesterolaemia. Damage or loss of endothelial cells can predispose the atherosclerotic vessels to vasospasm and can leave vessels unprotected against vasoconstrictor stimuli. The development of the WHHL model has not only given insight into the mechanisms of development of familial hypercholesterolaemia but has also provided a model for assessing various therapeutic approaches for the prevention and treatment of atherosclerosis.     

Phagocytic activity of the reticulohistiocyte system in rabbits after splenectomy and activation with ink

The survival rate was measured of differently aged rabbit erythrocytes that had been taken from young animals, tagged with 51Cr and injected into young and old animals. The recipient animals had either been splenectomized, or had an ink-activated reticulohistiocyte system, or both. In young as well as in old ink-treated animals the injected cells lived for a much shorter time than in the non-treated animals. In splenectomized animals the red blood cells lived a little longer than those in the control group. In animals which had been both splenectomized and ink-treated the 51Cr-tagged cells again lived for a shorter time than those in the control group, but longer than in the ink-treated animals.     

Effect of iron overload and iron deficiency on atherosclerosis in the hypercholesterolemic rabbit

It has been suggested that iron plays an important role in the pathogenesis of atherosclerosis, primarily by acting as a catalyst for the atherogenic modification of LDL. Although some epidemiological data suggest that high stored iron levels are an independent risk factor for coronary artery disease and that iron has been detected in both early and advanced atherosclerotic lesions, the evidence is often contradictory and inconclusive. We used the New Zealand White rabbit to investigate the effects of iron overload (FeO) and iron deficiency (FeD) on atherosclerosis. Groups of 7 rabbits were either iron loaded by injections of iron dextran (FeO group), iron depleted by phlebotomy (FeD group), or given injections of saline (control group) for a total of 9 weeks. All rabbits were fed a chow diet containing 1% (wt/wt) cholesterol for the last 6 weeks of the study. Iron and antioxidant status and cholesterol levels were assayed in plasma before cholesterol feeding (week 3) and at the time that the rabbits were killed (week 9). In addition, the susceptibility of LDL to oxidation was measured and pathological examination of the aortic arch and thoracic aorta performed at the end of the study. FeD significantly decreased the levels of blood hemoglobin, serum iron, and transferrin saturation compared with controls. Conversely, FeO significantly increased transferrin Fe saturation. FeO but not FeD decreased plasma cholesterol levels compared with control animals both before (P < .05) and after (P = .055) cholesterol feeding. Neither FeO nor FeD had a significant effect on the levels of antioxidants and lipid peroxidation products in plasma and aortic tissue or on the susceptibility of LDL to ex-vivo oxidation. FeO significantly decreased aortic arch lesion formation by 56% compared with controls (P < .05), whereas FeD had no significant effect. These results indicate that in this animal model, FeO decreases rather than increases atherosclerosis, likely because iron dextran exerts a hypocholesterolemic effect. Our data do not support the hypotheses that elevation of Fe stores increases or that a reduction of Fe stores by phlebotomy decreases the risk of coronary artery disease.     

Cellular mechanism of opioid tolerance

With advancing age, a series of structural, architectural and compositional modifications take place in the vasculature. The diameter of the vessels tends to increase, and thickening of intimal and medial layers is often observed. In the subendothelial space, blood-derived leukocytes and an increased amount of "activated" smooth muscle cells are present. Extracellular matrix accumulates and becomes particularly rich in glycosaminoglycans. Collagen content increases, while elastin fibers appear progressively disorganized, thinner, and frequently fragmented. These changes in the normal architecture of the vessel wall, that could be referred to as "the vasculopathy of aging", are likely to be the consequence of adaptive mechanisms to maintain normal conditions of flow, mechanical stress and/or wall tension. Although many of these features are similar to the histological findings of the atherosclerotic vessels, atherosclerosis and age-related "vasculopathy" are two distinct phenomena. Nonetheless, several experimental observations in animal models suggest a special link between "the vasculopathy of aging" and atherosclerotic disease, and suggest a particular predisposition of the old vessel to develop the atherosclerotic lesion. Compared to vessels from young animals, older ones show a greater reactivity to mechanical injury and to chronic insults. This may reflect changes in the biology of the vessels that are "intrinsic" to the aging process. Indeed, aging affects the function and responsiveness of the endothelium and vascular smooth muscle cells. Endothelial permeability is increased with age, while ability to produce vasoactive substances declines. Smooth muscle cells from old individuals show a growth advantage over the young ones, and display an increased ability to migrate toward chemoattractants. Moreover, the accumulation of advanced glycation end products (AGEs) occurring with aging can trigger a series of cellular events, such as cellular oxidative stress, expression of leukocyte adhesion molecules, endothelial transmigration of monocytes, and smooth muscle cell chemotaxis, all considered important prelesional events in the atherogenesis process. Taken together, the changes occurring with aging, while unproven to initiate lesion formation per se, are likely to accelerate the development of the atherosclerotic plaque and contribute to increased severity of this disease in the elderly.     

The rate constant K37 in complement fixation tests: kinetic studies on the influenza virus-immune complex model (author''s transl)

Diurnal variations in serum hormone levels during 2 different stages of prepubertal development were investigated in male and female rats. Groups of 13 to 18 and 25 to 30 day old male and female rats were decapitated at 4-hour by intervals during a period of 24 h. Their blood was collected and hormones were measured by radio-immunoassay. FSH levels were constantly high in 13 to 18, but low in 25 to 30 day old females. FSH was low in younger males, and significantly higher but without diurnal fluctuations in the older males. Serum LH was low in approximately 40% of the 13 to 18 day old females, while 40% had moderately high levels, and the remaining females extremely high levels of the hormone. Most of the extremely high LH peaks were found at 15.00 h and some at 03.00 h. Older females and males of both age groups had constantly low serum LH levels. Serum oestradiol was high in males and females during days 13 to 18, but it was lower in the 25 to 30 day old animals. In the young females prolactin was slightly elevated between 15.00 h and 19.00 h, while in the males the serum prolactin fluctuations were not significant. Serum testosterone was low in females at all times. The 13 to 18 day old males had higher testosterone levels than the 25 to 30 day old males. Both groups showed slight, but insignificant fluctuations in serum testosterone.     

Complement C6 deficiency protects against diet-induced atherosclerosis in rabbits

Low-density lipoprotein (LDL) can be transformed to an atherogenic moiety by nonoxidative, enzymatic degradation. Enzymatically degraded LDL induces macrophage foam cell formation, provokes release of cytokines, and also activates complement. To determine whether complement activation may contribute to atherogenesis, 6 pairs of homozygous C6-deficient rabbits and their non-C6-deficient heterozygous siblings were fed a cholesterol-rich diet for 14 weeks. Cholesterol levels and plasma lipoprotein profiles of the animals in the C6-competent and C6-deficient groups did not significantly differ, and the high density lipoprotein and LDL cholesterol ratios at the end of the experiment were 0.07+/-0.01 and 0.08+/-0.01 (SEM), respectively. However, differences in atherosclerotic plaque formation were discernible macroscopically, with extensive aortic lesions being visible in all C6-competent animals and absent in all C6-deficient animals. Aortas were sectioned from thorax to abdomen, and 10 sections were stained from each aorta. Quantification of atherosclerotic lesions and lumen stenosis with the use of computer-based morphometry documented a dramatic protective effect of C6 deficiency on the development of diet-induced atherosclerosis. We conclude that the terminal complement sequence is centrally involved in atherosclerotic lesion progression.     

Complicated atherosclerosis of the ascending aorta as a cause of recurrent cerebral embolisms in young adulthood

The authors report the case of a young woman (47 yrs old) who underwent cardiac evaluation for recurrent unexplained cerebral transient ischemic attacks. In the search for a source of embolization, a transesophageal echocardiography was performed and this revealed an atherosclerotic complex plaque of the ascending aorta as the sole potential source of cerebral embolism, while the remaining aortic wall was normal. The atheroma showed a calcific portion inserted on the aortic wall and a mobile hypoechogenic portion protruding into the aortic lumen. Furthermore, we found increased levels of cholesterol, fibrinogen and plasmatic homocysteine after methionine loading. Atherosclerotic lesions of the aortic arch are a rare cause of embolism in young patients with stroke, but they can lead to important complications such as thrombosis and embolism, similar to atherosclerotic lesions in elderly patients. The mechanisms that predispose for atherosclerosis of the aorta in young patients are still unknown. It was recently reported that not only hypercholesterolemia but also elevated levels of fibrinogen and homocysteine are independent risk factors for cerebrovascular disease. It is possible that these factors may be important predictors of atherosclerosis of the thoracic aorta in young patients, but more clinical data are still necessary. This case report confirms the importance of performing a TEE study and examining the cholesterol, fibrinogen and homocysteine plasmatic concentrations in all of young patients with unexplained stroke or transient ischemic attacks.     

Correlations of C1q- and C3d-bearing circulating immune complexes with immunopathological disease activity in lupus nephritis patients

The serum levels of circulating immune complexes (CIC) measured by three different types of enzyme immunoassay (EIA) using monoclonal anti-C1q and antibodies and C1q as solid phase reagents were compared with clinical disease activity and immunohistological glomerular lesions in 29 SLE patients. Three types of CIC measured by these assays (anti-C1q CIC, anti-C3d CIC and C1q SP CIC) showed significantly higher levels in patients than in controls and were significantly associated with the clinical and serological disease activities. Anti-C1q CIC showed good correlation not only with mesangial IgG depositions (P < 0.01), but also with that of C1q (P < 0.05). C1q SP CIC also showed a weak correlation with mesangial C1q deposition (P < 0.05). Serum levels of anti-C3d CIC increased with the degree of mesangial IgG and complement depositions. Analysis of the clinical course of a patient with active SLE revealed a more rapid decrease of anti-C1q CIC and anti-C3d CIC along with the improvement of disease activity, including the mesangial lesion, than that of C1q SP CIC. According to these results, the CIC detected with assays using monoclonal antibodies against complement fragments, especially the anti-C1q assay, is likely to provide specific information regarding the clinical, serological and immunohistological disease activity in lupus nephritis.     

Deafness-induced plasticity in the mature central auditory system

Studies in rats and guinea pigs indicate that local changes in inhibitory transmitters may underlie deafness-induced plastic changes in electrophysiological responsiveness of cells of the mature central auditory system. Following 21 days of bilateral deafness there is an increase in evoked Fos-immunoreactive neurones in the central nucleus of the inferior colliculus (CIC) to contralateral cochlear electrical stimulation, compared with normal or 1-day deafened animals. Deafness is also associated with a dramatic reduction in the population of CIC neurones that respond with suppression of activity to electrical stimulation. Moreover, in vivo microdialysis reveals a marked decrease in gamma-aminobutyric acid (GABA) release from the CIC cells in deafened animals. The results may have general implications for the mediation of central nervous system plasticity induced by deafferentation of sensory input.     

The influence of age on blood alcohol levels and ethanol-associated immunosuppression in a murine model of ethanol consumption

Several study findings indicate that with ethanol ingestion a number of changes occur in the immune system. We studied the effects of ethanol consumption on mice at various ages. We used a murine model in which young (age 6-8 weeks), middle-aged (age 12 months), and old (age 24 months) male C57Bl/6 mice were pair-fed either a Leiber-DeCarli liquid diet containing 7% (v/v) ethanol or an isocaloric control diet. Consumption of ethanol diet for 8 days resulted in high blood alcohol levels in young and old mice; low levels were observed in middle-aged mice. Middle-aged mice consumed more ethanol than did either young or old mice and had the lowest percent body weight loss of all three age groups. Proliferation of spleen lymphocytes to T-cell stimuli (concanavalin A and alloantigens) in both young and old mice fed ethanol was diminished. T-cell function was unchanged in middle-aged mice consuming an ethanol diet when compared with that observed in age-matched mice pair-fed control diet. No effect of ethanol on proliferation to lipopolysaccharide was noted in any group. Proliferative response of T cells to soluble anti-CD3 monoclonal antibody was also decreased in middle-aged and old pair-fed control mice when compared with young control mice. The proliferative response to soluble anti-CD3 in all three age groups of mice fed ethanol, however, was not significantly affected by ethanol consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related alteration in processing of temporal sound features in the auditory midbrain of the CBA mouse

The perception of complex sounds, such as speech and animal vocalizations, requires the central auditory system to analyze rapid, ongoing fluctuations in sound frequency and intensity. A decline in temporal acuity has been identified as one component of age-related hearing loss. The detection of short, silent gaps is thought to reflect an important fundamental dimension of temporal resolution. In this study we compared the neural response elicited by silent gaps imbedded in noise of single neurons in the inferior colliculus (IC) of young and old CBA mice. IC neurons were classified by their temporal discharge patterns. Phasic units, which accounted for the majority of response types encountered, tended to have the shortest minimal gap thresholds (MGTs), regardless of age. We report three age-related changes in neural processing of silent gaps. First, although the shortest MGTs (1-2 msec) were observed in phasic units from both young and old animals, the number of neurons exhibiting the shortest MGTs was much lower in old mice, regardless of the presentation level. Second, in the majority of phasic units, recovery of response to the stimulus after the silent gap was of a lower magnitude and much slower in units from old mice. Finally, the neuronal map representing response latency versus best frequency was found to be altered in the old IC. These results demonstrate a central auditory system correlate for age-related decline in temporal processing at the level of the auditory midbrain.     

Heart rate, blood pressure, and running speed responses to mesencephalic locomotor region stimulation in anesthetized rats

Responses of aging brain to physical training was evaluated by quantifying the substrates, glucose, lactic acid, and nucleic acids in cerebral cortex (CC) and medulla oblongata (MO) of the brain in rats. Rats of 1 month (young), 6 months (adult), 12 months (middle-aged) and 18 months (old) of age were swim-trained for 30 days. Glucose content of CC and MO increased with training whereas blood glucose decreased in trained young and adult animals with middle-aged and old animals maintaining constant blood glucose. Brain lactate in these two regions decreased with training in all age groups. However, the old animals showed an elevation in blood lactic acid in trained state, while the other age groups showed a decrease. Nucleic acid content, decreased with age, especially the RNA content in MO showing a larger depletion. However, there was no discernible influence of physical exercise on these parameters. Physical training has influenced the aging brain's adaptability, as seen by increase in its glucose content in young animals and also possible utilization of lactate as an additional substrate in old animals as evidenced by an increase in blood lactic acid.