Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats

Author(s):  
Milica R Prvulovic ◽  
Desanka J Milanovic ◽  
Predrag Z Vujovic ◽  
Milena S Jovic ◽  
Selma D Kanazir ◽  
...  

Abstract The current study aims to determine the potential benefits of calorie restriction (CR), one of the most promising paradigms for life span and healthspan extension, on cognitive performances in female Wistar rats during aging. As a measure of a healthspan, we evaluated the effects of different onset and duration of CR on frailty level. Female Wistar rats were exposed to either ad libitum (AL) or CR (60% of AL daily intake) food intake during aging. Two different CR protocols were used, life-long CR with an early-onset that started at the adult stage (6 months) and 3-month-long CR, started at the middle (15 months) and late-middle (21 months) age, thus defined as a late-onset CR. The effects of CR were evaluated using open-field, Y-maze, and novel object recognition tests. We broadened 2 tools for frailty assessment currently in use for experimental animals, and in alignment with our previous study, we created a physical–cognitive frailty tool that combines both physical and cognitive performances. Our results clearly showed that CR effects are highly dependent on CR duration and onset. While a life-long restriction with an early-onset has been proven as protective and beneficial, short-term restriction introduced at late age significantly worsens an animal’s behavior and frailty. These results complement our previous study conducted in males and contribute to the understanding of sex differences in a response to CR during aging.

1974 ◽  
Vol 63 (2) ◽  
pp. 285-298 ◽  
Author(s):  
F. DÖCKE ◽  
G. DÖRNER

SUMMARY Experiments were performed in female Wistar rats on the mode of action of oestrogen in affecting gonadotrophin secretion during infancy. Using an improved implantation method, former findings on a hypophysial site of oestrogen action in the Hohlweg effect were confirmed. The sensitivity to the ovulation-inducing effect of oestradiol benzoate (OB) increased as the rats approached the age of natural puberty. The first spontaneous ovulation could be suppressed by intrahypophysial, but not by intrahypothalamic, progesterone implants. A single s.c. injection or intracranial administration of OB at 25 or 26 days of age, although leading to premature vaginal opening (VO) and, in some of the animals, to one ovulation, did not induce true precocious puberty. To accelerate the onset of puberty, 0·05 μg OB/100 g body wt had to be injected daily from 5 days of age to VO, or from day 5 to day 10 and, additionally, from day 26 to VO. After long-term oestrogen treatment, the gonadotrophin-inhibiting effect of OB implanted into the middle hypothalamus from 26 to 34 days of age was significantly reduced in comparison with untreated control rats. A final experiment demonstrated that the first ovarian cycle was not prolonged after neonatal ovariectomy and implantation of ovaries at 24, 28 or 32 days of age. The results indicate that similar neurohormonal mechanisms are operational at the first pubertal and at later cyclic ovulations. They also indicate that the maturation of the gonadotrophin-controlling mechanisms continues during infancy in the absence of ovarian steroids. It can be accelerated in Wistar rats by long-term, but not by short-term prepubertal oestrogen treatment.


2021 ◽  
Author(s):  
Juan Qiu ◽  
Baoxuan Zhang ◽  
Bing Bu ◽  
Shu Fang ◽  
Lihua Song

Abstract Background Chemotherapy-induced neutropenia (CIN) has been shown to be associated with improved clinical outcomes in patients with various solid tumors. The aim of this study was to investigate the relationship between the timing and degree of chemo-induced neutropenia (CIN) and short-term efficacy and survival in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL).Methods A retrospective study was conducted on 236 newly diagnosed DLBCL patients who received at least 6 cycles of R-CHOP (like) or CHOP (like) between January 2012 and December 2018. According to the occurrence time of CIN, subjects were divided into CIN-absent group, early-onset CIN group and late-onset CIN group. According to the degree of CIN, they were divided into CIN-absent group, mild (grade 1-2) CIN group, and severe (grade 3-4) CIN group. Short-term efficacy was evaluated after 4 cycles of treatment. The Kaplan-Meier method was used to draw the survival curve, and the Cox proportional hazards model was applied to determine the correlation between the timing and extent of CIN and clinical features, short-term efficacy, progression-free survival (PFS) and overall survival (OS).Results After 4 treatment cycles, the objective response rate (ORR) of the early-onset group was higher than that of in the late-onset group and CIN absent group (95.7% VS 88.4% VS 81.0%). Multivariate analysis, Ann Arbor staging, choice of treatment plan and CIN timing were the independent prognostic factors for OS and PFS. OS and PFS in the early-onset group were longer than those of in the absent group [OS (HR:0.241; 95%CI: 0.110-0.530; P < 0.001), PFS (HR: 0.313; 95%CI: 0.169-0.579; P < 0.001)] and late-onset group [OS (HR: 0.332; 95%CI: 0.161- 0.685; P = 0.003), PFS (HR: 0.376; 95%CI: 0.204-0.693; P = 0.002)].Conclusions The timing of CIN is an independent predictor of prognosis in DLBCL patients treated with R-CHOP (like) or CHOP (like) regimens, and patients with early-onset CIN have longer survival times. The degree of CIN is not an independent predictor of prognosis in patients with DLBCL.


1996 ◽  
Vol 88 ◽  
pp. 67 ◽  
Author(s):  
Germán Chamorro ◽  
María Salazar ◽  
Silvia Salazar ◽  
Joaquín Tamariz

1973 ◽  
Vol 29 (1) ◽  
pp. 87-93 ◽  
Author(s):  
G. G. Birch ◽  
I. J. Etheridge ◽  
L. F. Green

1. Young female Wistar rats were fed for 18 d on diets containing dextrose, 43 dextrose equivalent (DE) glucose syrup, fractions of 43 DE glucose syrup of high and low molecular weight or sucrose.2. All rats gained weight and showed no gross external abnormalities or significant dental caries scores.3. The concentrations of cholesterol, triglycerides, free fatty acids and glucose were determined in samples of liver and serum. Generally, these values tended to increase with increasing molecular weight of dietary carbohydrate in the order dextrose, glucose syrup fraction of low molecular weight, and glucose syrup fraction of high molecular weight.4. Rats given the high-molecular weight glucose syrup fraction were found to have caecums twice the normal size.


1970 ◽  
Vol 18 ◽  
pp. 74-83
Author(s):  
FA Gbore ◽  
A Ologundudu ◽  
AO Arowosegbe ◽  
TM Ologun ◽  
FA Jolade ◽  
...  

Context: Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides and other Fusarium species that grow on maize worldwide, has been documented to cause various physiological responses in animals. Consumption of lesser amounts of fumonisins at levels below those that cause overt toxicity may exert haematological, serum biochemical and/or histopathological effects in animals.   Objective: The effects of dietary FB1 on haematology, serum biochemistry and histopathology were assessed in female Wistar rats in a short-term toxicity study.   Materials and Methods: Thirty-nine mature female Wistar rats (Rattus norvegicus) weighing between 167.5 – 170.5 g were used in the study. The rats were assigned to diets containing 0.2, 10.0 and 20.0 mg FB1/kg constituting diets 1, 2 and 3, respectively. After 14 days of feeding, blood samples were obtained from four rats per treatment. The rats were sacrificed by cervical dislocation, eviscerated for organ collections and subsequently processed for histology.   Results: Significant differences in feed consumption and body weight gains were not observed. The final live weight of the rats, however, seemed to decline with an increase in dietary FB1 levels. Significant (P<0.05) alterations were observed in the haematological and serum biochemical parameters with increasing levels of dietary FB1. Diets containing different FB1 concentrations, the decreased values of PCV, Hb, erythrocyte and monocyte counts could be attributed to the FB1 effects on the blood-forming tissues in animals placed on diets 2 and 3 as compared to those fed diet 1. Also, histopathological changes were observed in the livers, kidneys, spleens and hearts of rats fed diets 2 and 3.   Conclusion: This study revealed that the No-observable adverse effect level (NOAEL) of dietary FB1 above which may cause significant physiological changes without overt toxicity for short-term toxicity study in female Wistar rats is <0.74 mg/kg bw per day.   Keywords: Blood; Rat; Mycotoxin; Fusarium verticillioides; Fumonisin B1; Histopathology. DOI: http://dx.doi.org/10.3329/jbs.v18i0.8779 JBS 2010; 18(0): 74-83


2011 ◽  
Vol 63 (4) ◽  
pp. 1031-1036 ◽  
Author(s):  
M. Hogas ◽  
A. Ciobica ◽  
Simona Hogas ◽  
Veronica Bild ◽  
L. Hritcu

Manganese is a very well known neurotoxic agent. It has been mainly linked to impaired motor skills and disturbed psychomotor development. However, very few aspects are known about the cognitive deficits and behavioral consequences of chronic manganese exposure. In this context, we report herein our findings regarding short-term spatial memory, motor and anxiety-like behavior assessments in male Wistar rats exposed for 45 days to two different doses (3 mg/kg b.w., i.p. and 10 mg/kg b.w., i.p.) of manganese. Behavior testing (Y-maze task and elevated plus maze) was performed after 45 days of manganese administration. Chronic manganese exposure in Wistar rats led to behavioral alterations consisting of cognitive deficiencies in the Y-maze task and anxiety/compulsive-like behaviors in the elevated plus maze, but no motor disturbances as tested by the number of arm entries in the Y-maze. Additional work is necessary to understand the longterm effects of different doses and dosing regimens of manganese on cognitive/affective and motor functioning.


2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Nelson Inacio Pinto Neto ◽  
Maria Elizabeth Sousa Rodrigues ◽  
Ana Claudia Losinskas Hachul ◽  
Mayara Franzoi Moreno ◽  
Valter Tadeu Boldarine ◽  
...  

Four-week-old female Wistar rats were divided into two groups and fed a control diet (C) or a hyperlipidic diet (H) for 4 weeks. Rats from each group underwent ovariectomy (OVX) or sham surgery (SHAM). They received C or H for the next four weeks. The body weight gain (BW), food efficiency (FE), and carcass lipid content were higher in the OVX H than in the SHAM H. The OVX H exhibited a higher serum leptin level than other groups. IL-6, TNF-α, and IL-10 content of mesenteric (MES) adipose tissue was lower in the OVX H than in the OVX C. IL-6, TNF-α, and IL-10 content of retroperitoneal (RET) adipose tissue was lower in the SHAM H than in the SHAM C. The SHAM H showed decreased TG relative to the SHAM C. Similar results were obtained in relation to IL-6Rα, TNFR1, TLR-4, and MyD88 contents in the MES and RET white adipose tissue among the groups. A hyperlipidic diet for 8 weeks combined with short-term ovariectomy decreases the cytokine content of MES adipose tissues but increases BW, enhancing FE and elevating serum leptin levels. These suggest that the absence of estrogens promotes metabolic changes that may contribute to installation of a proinflammatory process induced by a hyperlipidic diet.


Author(s):  
D.N. Collins ◽  
J.N. Turner ◽  
K.O. Brosch ◽  
R.F. Seegal

Polychlorinated biphenyls (PCBs) are a ubiquitous class of environmental pollutants with toxic and hepatocellular effects, including accumulation of fat, proliferated smooth endoplasmic recticulum (SER), and concentric membrane arrays (CMAs) (1-3). The CMAs appear to be a membrane storage and degeneration organelle composed of a large number of concentric membrane layers usually surrounding one or more lipid droplets often with internalized membrane fragments (3). The present study documents liver alteration after a short term single dose exposure to PCBs with high chlorine content, and correlates them with reported animal weights and central nervous system (CNS) measures. In the brain PCB congeners were concentrated in particular regions (4) while catecholamine concentrations were decreased (4-6). Urinary levels of homovanillic acid a dopamine metabolite were evaluated (7).Wistar rats were gavaged with corn oil (6 controls), or with a 1:1 mixture of Aroclor 1254 and 1260 in corn oil at 500 or 1000 mg total PCB/kg (6 at each level).


Author(s):  
Pramod P. Singhavi

Introduction: India has the highest incidence of clinical sepsis i.e.17,000/ 1,00,000 live births. In Neonatal sepsis septicaemia, pneumonia, meningitis, osteomyelitis, arthritis and urinary tract infections can be included. Mortality in the neonatal period each year account for 41% (3.6 million) of all deaths in children under 5 years and most of these deaths occur in low income countries and about one million of these deaths are due to infectious causes including neonatal sepsis, meningitis, and pneumonia. In early onset neonatal sepsis (EOS) Clinical features are non-specific and are inefficient for identifying neonates with early-onset sepsis. Culture results take up to 48 hours and may give false-positive or low-yield results because of the antenatal antibiotic exposure. Reviews of risk factors has been used globally to guide the development of management guidelines for neonatal sepsis, and it is similarly recommended that such evidence be used to inform guideline development for management of neonatal sepsis. Material and Methods: This study was carried out using institution based cross section study . The total number neonates admitted in the hospital in given study period was 644, of which 234 were diagnosed for neonatal sepsis by the treating pediatrician based on the signs and symptoms during admission. The data was collected: Sociodemographic characteristics; maternal information; and neonatal information for neonatal sepsis like neonatal age on admission, sex, gestational age, birth weight, crying immediately at birth, and resuscitation at birth. Results: Out of 644 neonates admitted 234 (36.34%) were diagnosed for neonatal sepsis by the paediatrician based on the signs and symptoms during admission. Of the 234 neonates, 189 (80.77%) infants were in the age range of 0 to 7 days (Early onset sepsis) while 45 (19.23%) were aged between 8 and 28 days (Late onset sepsis). Male to female ratio in our study was 53.8% and 46% respectively. Out of total 126 male neonates 91(72.2%) were having early onset sepsis while 35 (27.8%) were late onset type. Out of total 108 female neonates 89(82.4%) were having early onset sepsis while 19 (17.6%) were late onset type. Maternal risk factors were identified in 103(57.2%) of early onset sepsis cases while in late onset sepsis cases were 11(20.4%). Foul smelling liquor in early onset sepsis and in late onset sepsis was 10(5.56%) and 2 (3.70%) respectively. In early onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 21(11.67%), 19 (10.56%), 20(11.11%) and 33 (18.33%) cases respectively. In late onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 2 (3.70%), 1(1.85%), 3 (5.56%) and 3 (5.56%) cases respectively. Conclusion: Maternal risk identification may help in the early identification and empirical antibiotic treatment in neonatal sepsis and thus mortality and morbidity can be reduced.


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