Diets rich in cholesterol and/or saturated fats have been shown to be detrimental to cognitive performance. Therefore, we fed a cholesterol (2%) and saturated fat (hydrogenated coconut oil, Sat Fat 10%) diet to 16-month old rats for 8 weeks to explore the effects on the working memory performance of middle-aged rats. Lipid profiles revealed elevated plasma triglycerides, total cholesterol, HDL, and LDL for the Sat-Fat group as compared to an iso-caloric control diet (12% soybean oil). Weight gain and food consumption were similar in both groups. Sat-Fat treated rats committed more working memory errors in the water radial arm maze, especially at higher memory loads. Cholesterol, amyloid-β peptide of 40 (Aβ40) or 42 (Aβ42) residues, and nerve growth factor in cortical regions was unaffected, but hippocampal Map-2 staining was reduced in rats fed a SatFat diet, indicating a loss of dendritic integrity. Map-2 reduction correlated with memory errors. Microglial activation, indicating inflammation and/or gliosis, was also observed in the hippocampus of Sat-Fat fed rats. These data suggest that saturated fat, hydrogenated fat and cholesterol can profoundly impair memory and hippocampal morphology.

Although research suggests that ovariectomy (ovx) is detrimental to spatial cognition in young rats, little work has evaluated the cognitive effects of ovx in aged rats. The authors investigated the effects of ovx in aged rats using the water radial-arm maze. In Study 1, young rats and aged rats receiving ovx 1.5 months before testing outperformed aged rats receiving sham surgery or ovx 21 days before testing. In Study 2, young rats and aged rats receiving ovx 2.0 or 6.0 months before testing outperformed aged sham rats. Aged rats exhibited estradiol and elevated progesterone levels comparable to those of young rats. The findings suggest that 1.5-6.0 months, but not 21 days, of ovx improves spatial memory in aged rats. The hypothesis that long-term ovarian hormone loss is detrimental to spatial memory in aged rats was not supported. The authors hypothesize that removal of elevated progesterone levels is related to the ovx-induced cognitive enhancement.

The objective was to determine whether exogenous insulin and dietary energy interact to affect follicular development in gilts. In a 2 x 2 x 2 completely randomized design, main effects were level of dietary energy (5771 or 9960 kcal metabolizable energy/day beginning on Day 12 of the estrous cycle), insulin dosage (0 or 0.4 IU/kg twice daily beginning on Day 15 of the cycle), and day of cycle at ovary removal (Day 17 or Day 19). Percentage of follicles designated small (less than or equal to 3 mm diameter) decreased from Day 17 to Day 19 of the cycle, and the percentage of large follicles (greater than or equal to 7 mm) increased (p less than 0.05). Insulin interacted with day of the cycle (p less than 0.05) to affect distribution of medium (4-6 mm) and macroscopically atretic follicles. Percentage of atretic follicles increased from Day 17 to Day 19 in saline-treated (from 15.5% to 38.2%) but not in insulin-treated animals (6.3% to 10.7%). Percentage of medium (4-6 mm) follicles decreased from Day 17 to Day 19 in saline-treated gilts (from 41.7 to 16.6%) but not in insulin-treated gilts (39.8% to 35.1%). Intrafollicular testosterone and progesterone concentrations were not affected by treatments. In medium follicles, the ratio of estradiol to progesterone was greater (p less than 0.05) for insulin-treated gilts on Day 17 than for the other treatment combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Transplantation of neural tissue has been explored as a potential therapy to replace dead or dying cells in the brain, such as after brain injury or neurodegenerative disease. However, survival of transplanted tissue is poor, especially when the transplant recipient is of advanced age. Recent studies have demonstrated improvement of neuronal deficits in aged animals given a diet supplemented with blueberry extract. The present study focuses on the survival of fetal hippocampal transplants to young (4 months) or middle-aged (16 months) animals with or without dietary supplementation with blueberry extract. Results indicate that fetal hippocampus transplanted to middle-aged host animals exhibits poor survival characterized by reduced growth and compromised tissue organization. However, when middle-aged animals were maintained on a diet supplemented with 2% blueberry extract, hippocampal graft growth was significantly improved and cellular organization of grafts was comparable to that seen in tissue grafted to young host animals. Thus, the data suggest that factor(s) in blueberries may have significant effects on development and organization of this important brain region.

Fourteen lactating and cycling Holsteins in each of two summers were assigned randomly to pens in a free-stall barn either with or without overhead fans to study the effect of fan cooling on certain endocrine and behavioral responses during the estrous cycle. After an adjustment period of 8 d in the first summer and 21 d in the second summer, jugular cannulas were inserted, and 25 mg of PGF2 alpha were injected. After injection, blood samples were collected frequently for 84 h in the first summer and 88 h in the second summer, followed by collection three times weekly for 3 wk thereafter each summer. Rectal temperatures were lower in the group cooled by fans than in the control group each summer. Luteal progesterone secretion tended to be greater in the fan group each summer; area under the luteal phase curve was significantly higher than for controls during the second summer. There was tendency for more preovulatory surges of LH and higher estrous responses rates in the fan group during the second summer. Thus, fan cooling of lactating dairy cows for several weeks before anticipated breeding provides potential for more efficient reproductive performance during the summer.

The current study assessed neurotrophin protein levels in male and female rat brain tissues at four different ages ranging from postpuberty to senescence. In both sexes nerve growth factor (NGF) increased, and brain-derived neurotrophic factor (BDNF) decreased, from 4 to 24 months of age. Using a slightly older age for the young group, or a slightly younger age for the aged group, had profound effects on whether age effects were realized. There were no sex differences in the pattern of change in neurotrophin levels across age, and neurotrophin levels did not correlate with estrogen levels in females or estrogen or testosterone levels in males. The current findings suggest that profound changes in neurotrophin protein levels can occur within only a few months time, and that these changes influence whether age-related neurotrophin alterations are realized.Survival and functional maintenance of cholinergic neurons are dependent upon neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) (Granholm, 2000;Levi-Montalcini, 1987;Woolf, 1991). Given recent evidence that neurotrophins are related to cognition in rodents, changes in neurotrophin levels may be a critical link in the cascade of biological alterations resulting in cognitive deterioration that occurs in aging and age-related neurodegenerative disorders (Kaisho, Ohta, Miyamato, & Igarashi, 1999;Mizuno, Yamada, Olariu, Nawa, & Nabeshima, 2000;Sugaya et al., 1998). Some studies show that patients with Alzheimer's disease (AD) exhibit alterations in NGF and BDNF in various brain regions compared to age-matched controls, although such effects are not consistently reported (see Siegel & Chauhan, 2000, for review (Nishizuka et al., 1991) or no change (Alberch, Perez-Navarro, Arenas, & Marsal, 1991;Crutcher & Weingartner, 1991;Katoh-Semba, Semba, Takeuchi, & Kato, 1998;Narisawa-Saito & Nawa, 1996;Scott, Liang, Weingartner, & Crutcher, 1994;Taglialatela, Robinson, Gegg, & Perez-Polo, 1997) in hippocampal NGF. Although strain differences in age-related neurotrophin changes may account for some of the discrepancy between rat studies, there are conflicting findings even when comparing studies using the same rat strain (Larkfors et al., 1988).Differences in the age of respective young and old groups may account for some variability in the findings. Showing substantial variability, the age of the "aged" group has ranged from 18 to 33 months in different studies (Narisawa-Saito & Nawa, 1996;Yurek & Turner, 2001). The age of the young comparison group could also impact the young versus aged comparison, as underscored by research showing significant alterations in NGF and BDNF concentrations during early development (Katoh-Semba, 1997;Nishizuka et al., 1991). In some studies the age of the "young" group was 1 month (Katoh-Semba et al., 1998), 3 to 4 months (Nishizuka et al., 1991), 3 to 5 months (Bimonte, Nelson, & Granholm, 2002), or 4 to 5 months (Yurek & Turner, 2001), whereas others collapsed across 2 to 5 months olds (Scot...

Given the established importance of glial cell line-derived neurotrophic factor (GDNF) in maintaining dopaminergic neurotransmitter systems, the nigrostriatal system and associated behaviors of mice with genetic reduction of its high-affinity receptor, GDNF receptor (GFR)α-1 (GFRα-1 +/− ), were compared with wild-type controls. Motor activity and the stimulatory effects of a dopamine (DA) D1 receptor agonist (SKF 82958) were assessed longitudinally at 8 and 18 months of age. Monoamine concentrations and dopaminergic nerve terminals in the striatum and the number of dopaminergic neurons in the substantia nigra (SN) were assessed. The results support the importance of GFRα-1 in maintaining normal function of the nigrostriatal dopaminergic system, with deficits being observed for GFRα-1 +/− mice at both ages. Motor activity was lower and the stimulatory effects of the DA agonist were enhanced for the older GFRα-1 +/− mice. DA in the striatum was reduced in the GFRα-1 +/− mice at both ages, and tyrosine hydroxylase-positive cell numbers in the SN were reduced most substantially in the older GFRα-1 +/− mice. The combined behavioral, pharmacological probe, neurochemical and morphological measures provide evidence of abnormalities in GFRα-1 +/− mice that are indicative of an exacerbated aging-related decline in dopaminergic system function. The noted deficiencies, in turn, suggest that GFRα-1 is necessary for GDNF to maintain normal function of the nigrostriatal dopaminergic system. Although the precise mechanism(s) for the aging-related changes in the dopaminergic system remain to be established, the present study clearly establishes that genetic reductions in GFRα-1 can contribute to the degenerative changes observed in this system during the aging process.

Transplantation of neural tissue has been attempted as a treatment method for neurodegenerative disorders. Grafted neurons survive to a lesser extent into middle-aged or aged hosts, and survival rates of < 10% of grafted neurons is common. Antioxidant diets, such as blueberry, can exert powerful effects on developing neurons and blood vessels in vitro, but studies are lacking that examine the effects of these diets on transplanted tissues. In this study, we examined the effects of a blueberry diet on survival, growth, and vascularization of fetal hippocampal tissue to the anterior chamber of the eye of young or middle-aged female rats. Previous work from our group showed significant increase in neuronal survival and development with blueberry diet in grafts. However, the effects of antioxidant diet on vascular development in grafts have not been explored previously. The age of the host affected individual vessel morphology in that aged hosts contained grafts with thick, undeveloped walls, and wider lumen. The blood-brain barrier also appeared to be affected by the age of the host. The blueberry diet did not affect vessel morphology or density of vessel-associated protein markers but gave rise to significantly increased growth capacity, cytoarchitecture, and the final size of hippocampal grafts.