大鼠大脑白质及白质内有髓神经纤维的性别与年龄差异

目的:研究正常年轻和中老年组雌雄性大鼠大脑白质及白质内有髓神经纤维之间的性别差异,并探讨大脑发育过程中性别差异随年龄增加的改变。方法:运用透射电子显微镜和体视学方法对6~8月龄的年轻Long-Evans大鼠及18月龄同种中老年大鼠大脑白质及其有髓神经纤维进行定量研究。结果:年轻组雄性大鼠大脑白质、有髓神经纤维及其髓鞘的总体积均显著大于雌性,而中老年组雌性大鼠大脑白质、有髓神经纤维体积密度、有髓神经纤维及其髓鞘的总体积均显著大于雄性。结论:年轻组及中老年组大鼠大脑白质、白质内有髓神经纤维及其髓鞘总体积均存在性别差异,随着年龄的增长,雄性大鼠大脑白质及白质内有髓神经纤维体积的减少较雌性更为明显。     

‘When an old rat smells a cat’: A decline in defense-related, but not accessory olfactory, Fos expression in aged rats

Comparisons were made between young (3-6 months) and aged (20-30 months) Wistar rats on locomotor activity, emergence, social interaction and cat odor avoidance. Aged rats were less active and spent less time in the open field during the emergence test than younger rats. Older rats also showed fewer contacts with a novel conspecific in the social interaction test, although total duration of interaction did not differ. There were very few behavioral differences between male and female rats. Older rats were less reactive than younger rats in a test of cat odor avoidance. However, they expressed similar amounts of cat odor-induced Fos in the posterior accessory olfactory bulb, a critical region for processing the predator odor stimulus. Older rats had reduced Fos expression in several defense-related brain regions that are normally activated by predator odors such as the medial amygdala and dorsal premammillary nucleus. These results indicate that aged rats are less reactive than younger rats to predator odors due to decreased responsiveness in defense-related but not necessarily olfactory circuits.     

Age-related impairment in complex maze learning in rats: relationship to neophobia and cholinergic antagonism

Scopolamine was utilized to assess cholinergic muscarinic blockade on the performance of young (3 months) and aged (23 months) male F-344 rats in a 14-unit T-maze task. Prior to training, a portion of each age group received a gustatory neophobia test (percent consumption of a novel sucrose solution) to assess involvement of norepinephrine systems implicated in age-related impairments of rats in other memory tasks. All rats were pretrained in one-way active avoidance (1.0 mA) on 3 consecutive days. Rats meeting criterion (8/10 avoidances on last day) began maze training the next day consisting of 10 trials on 2 consecutive days. The task required the rat to negotiate each of 5 maze segments within 10 sec to avoid scrambled footshock (1.0 mA). Rats received an intraperitoneal injection of either scopolamine hydrochloride (0.5 mg/kg or 0.75 mg/kg) or saline vehicle 30 min prior to maze testing. Consistent with past reports, aged rats were more neophobic (i.e., consumed less sucrose) than were young rats, but the degree of neophobia was not significantly correlated with maze error performance in either age group. Also consistent with previous studies, aged rats were significantly impaired, compared to young counterparts, in all maze performance measures including errors, alternation errors, runtime, and shock frequency and duration. Significant scopolamine-induced deficits were observed in both age groups, but only in errors and alternation strategy. No age by drug interaction was manifested in any performance measure indicating that scopolamine impaired learning of young and aged rats equivalently.(ABSTRACT TRUNCATED AT 250 WORDS)     

Naltrexone reverses age-induced cognitive deficits in rats

We evaluated young (3-4 months) and aged (22-24 months) male Sprague-Dawley rats in an attentional set-shifting procedure that assessed reversal, intradimensional shift (IDS), and extradimensional shift (EDS) discrimination learning tasks within one test session. These aspects of discrimination learning are sensitive to damage to distinct regions of frontal cortex. Compared to young animals, aged rats were significantly impaired on the EDS task and did not demonstrate significant impairment on the reversal or IDS tasks. The opioid antagonist naltrexone (2mg/kg, ip) was administered to young and aged rats prior to testing to assess possible improvements in aged-related cognitive impairments. Naltrexone (2mg/kg) attenuated the impairments in cognitive function in the EDS task for aged animals, but did not alter any task performance in the younger group. These results suggest that normal aging in rats is associated with impaired medial frontal cortex function as assessed by this attentional set-shifting procedure and opioid mediated mechanisms may represent a therapeutic target for drugs to improve cognitive deficits associated with aging.     

Age and sex-dependent decreases in ChAT in basal forebrain nuclei

Microdissection techniques were utilized to measure the activity of choline acetyltransferase (ChAT) (enzyme responsible for synthesis of acetylcholine) in individual basal forebrain nuclei of aged (24 month) and young (4 month) male and female rats. Small but consistent decreases in the activity of ChAT in aged rats were found, and the location of the changes was dependent on the sex of the rat. Aged female rats showed approximately 30% lower ChAT and 40% lower acetylcholinesterase (AChE) activity in the ventral globus pallidus (vGP). Aged males did not show decreased ChAT in the vGP but activity in the medial aspect of the horizontal diagonal band nucleus was 50% lower than in the young males. ChAT activity in four other closely aligned basal forebrain nuclei was not different between the young and aged rats. Analysis of cell number, density and area in the vGP by AChE histochemistry showed no significant differences between aged and young females. In addition, age and sex-dependent changes were measured in pituitary glucose-6-phosphate dehydrogenase activity. The relationship of the changes to age-dependent decrements in memory, the possible influence of gonadal hormones on aging, and the mechanisms responsible for age-related declines in ChAT activity are discussed.     

The capacity to develop maternal behavior is enhanced during aging in rats

The induction of maternal behavior (MB) in response to stimulation by pups was studied in aged rats (19-20 months old). We used virgin female rats, neonatally androgenized female rats and male rats. Both groups of female rats showed a constant estrous vaginal smear. Maternal responsiveness was compared with that of young rats (3-4 months old). Normal and androgenized female aged rats showed a very high percentage of immediate maternal responsiveness and 100% of the rats were fully maternal within 24 hr of testing. The percentage of cyclic and androgenized young rats showing MB were significantly lower. Chronic ovariectomy performed 17 months before testing but not acute ovariectomy abolished MB. Estrogen treatment (5 micrograms 15 hours before pup presentation) to chronically ovariectomized aged rats was not sufficient to reestablish significantly the capacity of the normal female aged rats to become short-latency maternal. Young and aged male rats showed no difference in maternal responsiveness to the presence of foster pups. The percentage of maternal aged male rats was significantly lower than that of the normal and androgenized aged female rats, whereas young male and female rats showed a similar level of MB, indicating a sex difference in the development of MB with age. In conclusion the high percentage of rats becoming maternal and the short-latency maternal responsiveness in aged female rats appears to be the result of a prolonged estrogen and/or prolactin stimulation.     

The plasma catecholamine stress response is characteristic for a given animal over a one-year period

The same male and female rats with indwelling jugular catheters were stressed (immobilization) on two occasions at the ages of 3 to 4 and 15 to 16 months. Plasma levels of the catecholamines (CA) norepinephrine (NE) and epinephrine (E) were determined before and during stress at each session. During stress, plasma NE and E levels increased markedly. At the younger age, female animals showed markedly higher CA levels than male animals. After one year, stress CA levels were higher for both sexes, but had increased markedly in male and little in female animals. A positive correlation was found between the plasma CA stress response of individual animals at both sessions; this correlation was stronger for males and NE. This indicates that "high" responders usually remain high responders, "low" responders remain low and intermediate responders intermediate. In conclusion, the plasma CA stress response increases markedly in male, but little in female rats over the period of 1 year and the relative magnitude of the individual stress response remains a characteristic of each given animal.     

Age-related sex differences in spatial learning and basal forebrain cholinergic neurons in F344 rats

Basal forebrain cholinergic neurons are important for spatial learning in rodents. Spatial learning ability is reportedly better in males than females, and declines with age. To examine the role of cholinergic function in sex- or age-related differences in spatial learning, we compared the size of basal forebrain cholinergic neurons (BFCN) of young and aged male and female Fischer 344 (F344) rats that had been trained in the Morris water maze. Young male and female rats were equally proficient in finding the platform during training trials, but probe tests revealed that young male rats had better knowledge of the platform's precise location. Impairments in spatial learning were observed in aged rats, and the advantage of males over females was lost. BFCN were significantly larger in young male than young female rats, and were correlated with spatial memory performance for both groups. BFCN were smaller in aged than young males; no change was seen between young and aged females. In the groups of aged rats the correlation between neuron size and spatial memory was lost. The present findings provide further evidence of a role for the basal forebrain cholinergic system in spatial learning, but reveal a complex interaction between sex, age and behavioral performance.     

Comparison of developmental trajectories for place and cued navigation in the Morris water task

Previous studies investigating the development of place and cued learning using the Morris water task are in disagreement regarding the day in development that each type of learning emerges. Here, place and cued navigation in the water task were examined in differently aged groups of young male and female rats (P17, P18, P19, P20, and P24) during a single day of training. When only distal cues were present, P20 and P24 but not younger rats learned the location of the hidden platform. In contrast, when a proximal cue marked the platform location, rats as young as P17 showed evidence of cue-controlled navigation, although only P18 and older rats exhibited cued learning. In line with most previous studies, these results indicate that cued learning emerges earlier in development than place learning and support a dissociation of developmental trajectories for the neural systems underlying the two types of navigation.     

大鼠大脑白质及白质内有髓神经纤维老年性改变的体视学研究

目的 探讨老年大鼠大脑白质及白质内有髓神经纤维的改变.方法 运用透射电子显微镜和体视学方法分别对年轻组和老年组Long-Evans大鼠大脑白质及其内有髓神经纤维进行定量研究.结果 老年组大鼠大脑白质总体积,有髓神经纤维总长度分别下降了24.1%和41%;老年组大鼠有髓神经纤维体积密度、髓鞘体积密度和纤维直径分别增加了30%、23.9%和31%,具有统计学意义.但是有髓神经纤维长度密度、有髓神经纤维总体积和髓鞘的总体积没有显著老年性改变.结论 正常老年大脑的萎缩主要是由白质体积的下降引起的.正常老年大脑白质的有髓神经纤维总长度显著性降低,并且主要是由于白质内细小直径的有髓神经纤维丢失所造成的.     

Pattern of sensitization to common environmental allergens amongst atopic Singapore children in the first 3 years of life

This study was aimed to investigate the sensitization pattern to a range of common allergens in young Singaporean children. A cross-sectional study involving 75 children aged below 3 years was carried out. They presented between December 1995 and April 2000 with symptoms of asthma, rhinitis, eczema, or food allergy. Their levels of allergen-specific serum IgE to a panel of foods (egg white, milk, soy protein, shrimp, wheat and peanut), pet dander, dust mites and cockroaches were measured with Pharmacia CAP System radioallergosorbent test kits. Serum IgE levels greater than 0.35 kU/l represented a positive result. Four children could not be tested with the complete panel because of insufficient serum. The prevalence of sensitization was highest for cow's milk (45.9%) followed by egg white (38.7%), dust mites Dermatophagoides pteronyssinus (31.4%) and Blomia tropicalis (25.5%). Sensitization to ingested allergens was significantly more prevalent in children aged 1 year or younger than in the older children (70.4% of those below 1 year, and 50% of those aged 1-3 years; p < 0.02). Sensitization to inhaled allergens, such as dust mites, was more likely to manifest as respiratory symptoms (allergic rhinitis and asthma), while ingested allergens were associated with gastrointestinal symptoms and eczema (p < 0.001). It was concluded that infants and young children are at high risk of sensitization to common environmental substances. Allergen avoidance is therefore important even in the very young. The prevalence of sensitization to food allergens is higher compared to inhalant allergens in young children.     

Sex-difference in the age related change of cholesterol metabolism in rats

In Sprague-Dawley rats at the ages of 5 weeks (young) and 9 months (adult), the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in age-matched animals was significantly higher in females than in males. The magnitude of the age-related decrease in the reductase activity was also greater in female rats. When rats were fed a cholesterol-enriched (1%) diet for 30 h as cholesterol challenge, the reduction of reductase activity depended more on sex than on age. The activity of cholesterol 7 alpha-hydroxylase was also higher in female than in male rats and it apparently remained unchanged with age in female rats while it decreased in male rats. With a cholesterol-enriched diet, the hydroxylase exhibited a significant age- and sex-dependent difference and it increased only in young males and adult females. In male rats, the concentration of hepatic cholesterol was significantly higher in adult than in young rats while it was comparable in female rats. The increase in hepatic cholesterol with dietary cholesterol was observed only in male adult rats. A significant age-related difference was observed in the concentration of serum cholesterol. The results suggest an existence of sex-dependent compensatory mechanism for maintenance of hepatic cholesterol homeostasis with age.     

不同鼠龄大鼠颈总动脉内膜弹力纤维退行性变性的实验研究

目的 探讨颈总动脉分叉处内弹力膜超微结构的增龄变化,为临床防治老年性脑血管(多发)病提供实验依据.方法 24只Wistar大鼠,按月龄分为青年组、成年组和老年组,每组8只,快速分离各年龄组Wistar大鼠的颈总动脉分叉,热碱消化提纯内弹力膜,运用扫描电镜结合图像分析仪测量内弹力膜的窗孔数目和窗孔面积.结果 内弹力膜窗孔总数成年组(964.00±4.13)大于青年(710.00±1.22)和老年组(624.00±2.54),P<0.01,老年和青年组间差异无统计学意义(P>0.05);大窗孔数老年组(105.20±8.78)大于青年(13.00±1.10)和成年组(52.40±2.79),P<0.01,成年组大于青年组(P<0.01);窗孔面积百分比老年组(39.86±3.51)大于青年(15.52±1.70)和成年组(23.58±2.12),P<0.01,成年与青年组间差异无统计学意义(P>0.05).结论 随增龄颈总动脉分叉处弹性减少、窗孔变大,内膜对大分子物质的屏障性降低,可能是动脉粥样硬化和动脉瘤好发于颈总动脉分叉处的重要原因.     

Vasopressin prolongs behavioral and cardiac responses to mild stress in young but not in aged rats.

In young male Wistar rats sudden silence superimposed on low intensity background noise evokes a relative decrease in heart rate. This bradycardia is accompanied by immobility behavior. In the present study, involving young (3 month), late-adult (14 month), aged (20 month), and senescent (25 month) rats the magnitude of the stress-induced bradycardia shows an age-related reduction while the behavioral immobility response remained unchanged during the process of aging. Arginine-8-vasopressin (AVP, 6 micrograms/kg SC) administered 60 min prior to the experiment led to a prolonged behavioral and cardiac stress response in young and late-adult rats, but not in aged and senescent animals. The peripheral and central mechanisms possibly involved in the failure of systemically applied AVP to improve bradycardiac stress responses in aged rats are discussed.     

Social recognition memory: influence of age, sex, and ovarian hormonal status

Social recognition memory underlies many forms of rodent interaction and can be easily tested in the laboratory. Sex differences in aspects of this memory have been reported among young adults, and some studies indicate an age-related decline among male rats. In contrast, neither the impact of natural fluctuations in ovarian hormones nor the performance of aged female rats on social recognition memory has been previously evaluated. In experiments 1 and 2, the social recognition memory of young adult female Long-Evans rats (age 3-5 months) was compared during proestrus and estrus, and performance was found to be stable across estrous cycle phases. In experiment 3, the social recognition memory of young adults as compared to aged (16.5-19.5 months) rats was tested using the social discrimination procedure, following delays of 15, 45, 90 or 120 min. The estropausal status of aged female rats was tracked during the experiment but was not found to influence memory ability. Males of both ages investigated juveniles (both novel and familiar) more than did females, although despite this difference, both sexes demonstrated robust memory. Interestingly, only young adult females were capable of demonstrating memory following the longest delay. Collectively, our findings indicate that the pattern of age-related changes in social recognition memory is subtle and that aging does not greatly alter the behavioral sex differences observed among young adults.     

雄性大鼠大脑半球白质及其内有髓神经纤维老年改变的侧别差异

目的 探讨雄性大鼠左右大脑半球白质及其内有髓神经纤维是否存在显著性差异,以及每侧大脑半球白质及其内有髓神经纤维的老年性改变是否一致.方法运用透射电子显微镜和体视学方法分别对5只年轻(6～8月龄)和4只老年(18月龄)雄性Long-Evans大鼠左侧、右侧大脑半球白质体积及白质内有髓神经纤维体积、长度和直径进行定量研究.结果年轻组大鼠和老年组大鼠左右大脑半球白质体积及白质内有髓神经纤维体积、长度和直径均不存在显著性差异.每侧大脑半球白质及其内有髓神经纤维总长度和总体积均随年龄增加而降低,右侧半球白质体积、右侧半球白质内有髓神经纤维总体积和左侧半球白质内有髓神经纤维总长度随年龄增长分别显著性降低32.9%、28.6%和49.3%.结论正常年轻和老年雄性Tong-Evans大鼠两侧大脑半球的白质及其内有髓神经纤维均不存在显著性侧别差异.老年雄性Long-Evans大鼠右侧大脑半球白质体积、右侧大脑半球白质内有髓神经纤维的总体积和左侧大脑半球白质内有髓神经纤维总长度存在显著老年性改变.     

Cytotoxic effects of erythromycin estolate and chlorpromazine on hepatocytes isolated from rats of varying ages: A brief note

Hepatocytes isolated from young (1 month) rats were as sensitive to the cytotoxic effects of erythromycin estolate and chlorpromazine as were liver cells obtained from older (3, 10 and 24 months) rats. The hepatocytes from the 24-month-old rats released aspartate transaminase more slowly than did parenchymal cells isolated from the younger rats.     

Undernutrition in early life: lasting effects on activity and social behavior of male and female rats.

The growth-retarded offspring of mother rats undernourished throughout pregnancy and lactation were fed ad libitum from weaning. Males were tested at 100 days of age, and ovariectomized females at 150 days. After 2 weeks of isolation, pairs of males consisting of 1 control (C) and 1 previously undernourished (PU) rat were observed for 10 min on each of 9 consecutive days. Similarly paired and treated female rats were tested a total of 8 times, the first 3 tests being separated from the last 5 by a 10-day interval. The PU rats, whether male or female, performed more rearing responses and PU male rats ambulated more in the social situation than C rats. The PU males also performed more of the social responses allogroom, walk over, and mount than C males. Similarly, PU females performed more allogroom and crawl under than C females. In general, PU rats were more active than C rats and more socially responsive.     

慢性脑缺血对青年和老年大鼠海马NOS阳性神经元的影响

本文利用组织化学方法观察了慢性脑缺血对青、老年大鼠海马ＮＯＳ阳性神经元的影响。慢性脑缺血采用双侧颈总动脉永久性结扎模型。结果：青年缺血１ 月组大鼠海马ＣＡ１、ＣＡ２～３ 和ＤＧ 亚区ＮＯＳ阳性神经元面数密度分别为２９．１±２．３、２３．５±２．１ 和３９．３±２．８,小于对照组相应三个亚区（４９．６±１．３、４９．３±２．１ 和６４．７±２．１）,Ｐ＜ ０．０１;青年缺血３ 月组大鼠ＣＡ１、ＣＡ２～３ 和ＤＧ 亚区ＮＯＳ阳性神经元面数密度分别为４０．２±１．６、３９．３±２．５ 和４８．４±１．８,和对照组者相近,但大于缺血１ 月组（Ｐ＜ ０．０１）。老年缺血１ 月组大鼠海马各区ＮＯＳ阳性神经元面数密度分别为３９．６±１．５、３５．６±２．１ 和５４．７±２．５,小于老年对照组相应三个亚区（５５．８±１．７、５１．３±１．７ 和６４．９±１．９）,Ｐ＜ ０．０１;老年缺血３ 月组大鼠各亚区ＮＯＳ阳性神经元面数密度分别为４３．１±２．４、３８．７±３．４ 和５４．７±３．２,仍然小于对照组,Ｐ＜ ０．０１。结果提示：慢性脑缺血可以影响大鼠海马ＮＯＳ阳性神经元,但青年和老年大鼠海马ＮＯＳ神经元对慢性脑缺血损伤的易感性和反应性不同。     

Effect of stressor intensity on habituation and sensitization of glucocorticoid responses in rats

This experiment was designed to study the effect of stressor intensity on habituation/sensitization of the adrenocortical stress response in rats. Rats were given 18 shocks in 3-hr daily sessions for 8 days, and a single shock probe before the sessions was used to determine how adrenocortical responsiveness changed with repeated exposure to the stress sessions. When lower intensity shock was given, the changes in plasma corticosterone response to shock probes followed a U-shaped curve--with a response that first habituated to no-shock control levels but later returned to the same magnitude as seen on the 1st probe day. Plasma corticosterone responses in rats given higher intensity shock never habituated and instead demonstrated an increased response indicative of sensitization; a temporal delay of 1 week occurred before sensitization developed. Responsiveness to exogenous adrenocorticotropin 24 hr after the last stress session was monotonically related to the intensity of the stressor presented during the experimental sessions. These data are consistent with the rule from the habituation literature that stimulus intensity is inversely related to the magnitude of habituation. Thus the data extend the dual process theory of Groves and Thompson (1970) to an endocrine respondent. The data also suggest that an explanation as to discrepancies in the literature concerning adrenocortical response to repeated presentation of stressors may relate to differences in the stressor parameters used.