Normal Aged Rats Research Articles

Spatial learning impairment in aged rats: comparing between aged basal forebrain lesioned and normal aged rats

Normal aged rats (26 months) displayed significant impairments in learning the Morris water maze task as compared with young adult rats (3 months). The learning deficits of aged basal forebrain (BF)-lesioned rats (26 months; ethylcholine aziridinium ion was injected into the bilateral basal forebrain at 3 months age) were more severe than those of normal aged rats. Choline acetyltransferase (ChAT) in the frontal cortex of aged BF-lesioned rats activity was significantly reduced, but not in normal aged rats which level was almost the same as that in young adult rats. Histological examination showed that cholinergic fibers (acetylcholinesterase staining) in the frontal cortex reduced in aged BF-lesioned rats, but not in normal aged rats. The number of binding sites ( B max) for [ 3H]vesamicol, a ligand for the vesicular acetylcholine transporter, in the frontal cortex of normal aged rats was significantly less than that in young adult rats, while the B max of aged BF-lesioned rats was higher than that of normal aged rats. The levels of monoamines and their metabolites in the frontal cortex and striatum but not hippocampus of aged BF-lesioned rats were markedly reduced as compared with those of normal aged and young adult rats. These results taken together indicate that normal aged and aged BF-lesioned rats exhibit learning deficits and that the differences of the severity of spatial learning deficits between normal aged and aged BF-lesioned rats may be due to, at least in part, the different properties of cathecolaminergic, serotonergic and cholinergic dysfunctions in the discrete brain sites.

Increased NGF-like activity in young but not aged rat hippocampus after septal lesions

Sympathetic sprouting in the hippocampus following septal denervation is thought to involve nerve growth factor (NGF). This sprouting response is dramatically reduced in aged rats, but immunological assays reveal no age-related decline in hippocampal NGF levels. In the present study, both a bioassay and an immunoassay were used to examine the effect of a medial septal lesion on hippocampal NGF levels in young adult (2–5 months) and aged (24 months) Fischer 344 rats. No significant differences were detected between normal young and aged rats, in agreement with earlier results. Following medial septal lesions, however, only young rats demonstrated significant increases in hippocampal NGF-like activity. These results support the hypothesis that the age-related deficit in sympathetic sprouting results from an attenuated neurotrophic response to hippocampal denervation.

Effects of nicotinic agonists and antagonists on spatial working memory in normal adult and aged rats

AbstractThe present study had two goals (1) to examine the effects of treatments with nicotinic agonist (nicotine) and antagonist (mecamylamine) on working memory in normal adult rats (14 months of age), and (2) to determine if treating aged (36 to 42 months of age), memory‐impaired rats with nicotine could improve their memory function. Memory testing was carried out using a delayed non‐matching to position paradigm in a T‐maze. Rats were trained to run down one arm of the maze (e.g., right) on an information run and then, after a variable memory delay period of 10, 90, or 180 sec, run down the other arm (e.g., left). In normal adult rats after water injection, memory accuracy was inversely related to memory delay (> 90, 75, and 67% accuracy at the 10, 90, and 180 sec delays, respectively). Administration of nicotine (0.1 or 0.4 mg/kg), or mecamylamine (2.5 or 5 mg/kg), or combinations of these drugs had no significant effects on memory in these rats. However, mecamylamine alone or in combination with nicotine reduced running speed in the T‐maze in normal adults, indicating that the drugs did produce some behavioral effects. In aged rats, memory accuracy after water injection was much lower than that of younger adults, averaging 64, 57, and 50% at 10, 90, and 180 sec delays. Interestingly, nicotine injections of 0.1 or 0.4 mg/kg resulted in highly significantly improved accuracy in the memory task. The deficit in memory accuracy in aged rats, evident even at the shortest delay period (10 sec), suggests that the rats may have had impairments in attention or visual discriminatory ability. If this is so, then the beneficial effects of nicotine observed in this study may be more related to its effects on attention rather than memory directly. © 1994 Wiley‐Liss, Inc.

Controlled neonatal exposure to estrogens: a suitable tool for reproductive aging studies in the female rat.

The present study was designed to determine whether the modification of exposure time to large doses of estrogens provided a reliable model for early changes in reproductive aging. Silastic implants containing estradiol benzoate (EB) in solution were placed into 5-day-old female Wistar rats and removed 1 day (Ei1 group) or 5 days (Ei5) later. In addition, 100 micrograms [corrected] EB dissolved in 100 microliters corn oil was administered s.c. to another group (EI). Control rats received either vehicle implants or 100 microliters corn oil. Premature occurrence of vaginal opening was observed in all three estrogenized groups independently of EB exposure. However, females bearing implants for 24 h had first estrus at the same age as their controls and cycled regularly, and neither histological nor gonadal alterations could be observed at 75 days. Interestingly, they failed to cycle regularly at 5 mo whereas controls continued to cycle. On the other hand, the increase of EB exposure (Ei5, EI) resulted in a gradual and significant delay in the onset of first estrus and in a high number of estrous phases, as frequently observed during reproductive decline. At 75 days, the ovaries of these last two groups showed a reduced number of corpora lutea and an increased number of large follicles. According to this histological pattern, ovarian weight and progesterone (P) content gradually decreased whereas both groups showed higher estradiol (E2) content than controls. This resulted in a higher E2:P ratio, comparable to that observed in normal aging rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oestrogen on hypothalamic β-endorphin in ovariectomized and old rats

Immunocytochemical β-endorphin (β-EP) staining and ultrastructual observations in the hypothalamus were compared in normal mature female rats, ovariectomized rats, and aged female rats. The effects of oestradiol benzoate (EB) on the hypothalamus were studied. The female Wistar rats were divided into seven groups, as follows: 40-day-old rats (Mature), 54-day-old rats ovariectomized at 40 days (Ovx), rats ovariectomized at 40 days and injected with 0.1 mg EB daily for 7 days (Ovx + e), rats ovariectomized and injected with one dose of 1 mg EB (Ovx + E), 500-day-old (Old), old rats injected with 0.1 mg EB daily for 7 days (Old + e), and old rats injected with 1 mg EB (Old + E). In the Ovx and Old groups, β-EP-positive cells in the arucuate nucleus were rarely seen, as compared with the Mature group. The staining of β-EP-positive cells in Ovx + e was slightly recovered and that in Ovx + E was almost completely recovered. However, no recovery of β-EP-positive cells was seen in the Old + e or Old + E groups. The number of nerve fibers in the median eminence were reduced in both the Ovx and Old groups, as compared with the Mature group. There was no relationship between changes in these numbers and oestrogen replacement in the Old group, but in the Ovx group oestrogen replacement brought about recovery of these numbers. The number of glial cells increased after oestrogen replacement in both the Ovx and Old groups. The frequency of giant mitochondria in the neurons in the arcuate nucleus decreased after oestrogen replacement in the Old group.

Amyloid β protein precursor accumulates in swollen neurites throughout rat brain with aging

We immunocytochemically studied the expression of amyloid β protein precursor (APP) in the brains of normal aged rats, and found APP accumulation in swollen neurites, most of which were axons. These swollen neurites appeared throughout the central nervous system of aged rats; most of them were negative for neurofilament, ubiquitin, and tau. Such widely distributed APP accumulation in swollen neurites may reflect impaired fast axonal transport due to aging. APP immunostaining may be a good method to detect widely distributed age-related changes.

IMMUNOCYTOCHEMICAL STUDY OF AMYLOID β PROTEIN PRECURSOR IN MOUSE AND RAT BRAINS

We studied the immunocytochemical distribution of amyloid β protein precursor (APP) in the nervous systems of the mouse and the rat, and changes with aging and brain damage induced by intraventricular injection of kainic acid in the rat brains. We used three different antisera against synthetic peptides of APP and one monoclonal antibody against APP. On Western blot analysis, both antisera against carboxyl-and amino-terminal regions of APP recognized the same 106-122 KDa proteins from mouse brain. Immunocytochemically, APP immunoreactivity was located in all types of neurons and some glial cells in both the central and peripheral nervous systems. In the brains of normal aged rats, APP accumulated in swollen neurites, most of which were axons. These swollen neurites appeared throughout the central nervous system. In the rat brains injected with kainic acid, APP positive dystrophic neurites appeared around the track of the cannula after 3 h, neurons near the lesion showed increased APP immunoreactivity after 6 h, and reactive astrocytes expressed APP with Kunitz-type protease inhibitor domain in the lesion and ipsilateral hippocampus after 3 days. APP was expressed by neurons and glial cells throughout nervous systems, and these distributions changed with aging and brain damage.

Leupeptin causes an accumulation of lipofuscin-like substances in liver cells of young rats

Leupeptin, a thiol protease inhibitor, has previously been shown to cause a dense accumulation of substances resembling age pigment and called ceroid-lipofuscin, in brain cells of young rats [1]. Thus far, however, attempts to produce age pigments in hepatocytes of normal young rats with protease inhibitor(s) have not been successful. The present study provides the first demonstration that leupeptin induces lipofuscin-like substances in normal young rat hepatocytes. Male Fischer-344 rats (age 4–6 weeks) were continuously infused with leupeptin or saline i.p. for 2 weeks by an osmotic minipump (dosage, 1–50 mg/100 g per day). Liver tissues were then examined by light, fluorescence and electron microscopy. Both hepatocytes and non-parenchymal cells of livers treated with leupeptin, but not saline, showed a dense accumulation of pigments which stained deeply with toluidine blue, were PAS-positive and were brightly autofluorescent. After UV excitation the pigments had an emission spectrum with a broad peak at 480–540 nm extending to 650 nm resembling the spectrum of age pigment from livers of normal aged rats. Electron microscopic examination revealed numerous lipofuscin-like deposits with heterogeneous morphology in the cytoplasm of both hepatocytes and non-parenchymal cells; lipid and myelin-like bodies were also present in hepatocytes. The results indicate that the perturbation of proteolytic activity in liver by leupeptin causes an accumulation of substances which by several criteria resemble lipofuscin. These results thus provide further support for the ‘Protease Inhibitor Model of Lipofuscin Formation’ [2] as well as a potential experimental model for studying hepatocellular aging processes.

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, neon 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 μg 15 hours before pup presentation) to chronically ovariectomized aged rats was not sufficient to reestablish significantly t 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.

Anomalous accumulation of τ and ubiquitin immunoreactivities in rat brain caused by protease inhibition and by normal aging: a clue to PHF pathogenesis?

Rats received intraventricular infusion of leupeptin or saline and brain sections were immunostained with antibodies to τ (anti-HFoPHF) or ubiquitin. Results were compared with immunostaining on normal aged rat brains and Alzheimer's disease (AD) brains. Both antibodies stained Purkinje cell perikarya and dendrites of leupeptin (bu not salin)-treated and aged rat brains, as well as senile plaque neurites and neurofibrillary tangles in AD brains. The results are consistent with the hypothesis that paired helical filament (PHF) formation involves defective protein degradation.

Effects of antioxidants on the TBA reaction of various rat liver homogenates

The TBA reaction of physiologically normal (young and aged) rat liver homogenate appears to be catalyzed mainly by nonheme iron which is sensitive to EDTA, whereas some iron species which are not affected by EDTA seem to be functioning as catalysts in the TBA reaction of drug-intoxicated (CCl 4, HCB) liver homogenates.

Peripheral nerve abnormalities in aging rats.

The sciatic/tibial/plantar nerve complex of normal aged rats displays striking morphological changes that are most pronounced distally. Nerve fiber abnormalities include: (a) large numbers of axonal glycogenosomes, mitochondria, dense membranous bodies, and decorated particles; (b) adaxonal Schwann cell processes sequestering portions of axoplasm; (c) swollen demyelinated and remyelinated axons, some encircled by supernumerary cellular processes; and (d) collagen pockets, denervated Schwann cell columns, and empty basal laminae. Abnormalities a and b were encountered with increasing frequency on descent through the tibial and plantar nerves. Abnormalities b, c, and d were found in lateral and medial plantar nerves, where they were associated with an enlarged endoneurial space. Found in animals kept in cages with smooth or wire-mesh floors, the incidence of these changes increased with advancing age. They are attributed to trauma and ischemia from chronic pressure on the plantar nerve.

Comment on “Evapotranspiration from a small clay catchment” by R. K. Pegg and R. C. Ward”

Probiotic administration has been associated with enhanced immune function in elderly subjects. However, approaches for selection of an “ideal” strain of bifidobacteria are still difficult. The aim of the present study is to investigate the possible modulatory effects of three strains of Bifidobacterium species (Bifidobacterium adolescentis ATCC 15704, Bifidobacterium breve ATCC 15700 and Bifidobacterium longum ATCC 15707) on haematological and immunological parameters of aged albino rats corresponding to normal adult ones. The animals were divided into six groups; three groups of aged rats were fed yoghurt inoculated with one of the Bifidobacterium strains; one group of aged rats was fed yoghurt alone (control aged); two groups of adult and aged rats were provided with normal diet and assigned as normal groups. The total leucocyte count was significantly increased in the three bifidobacteria-treated aged groups as compared with both normal and control aged rats. Serum IgA level was considerably increased in all treated rats. On the contrary, serum IgE level was significantly decreased in rats supplemented with yoghurt inoculated with B. adolescentis or B. breve. Both B. adolescentis and B. breve groups showed significant enhanced production of TNF-α. Furthermore, the production of cytokine IL-8 was significantly increased in the B. adolescentis group. Interestingly, it was apparent that only B. adolescentis had the most pronounced effect on aged rats to regain nearly normal values as measured in normal adult rats. Conclusively, the present work indicates that dietary consumption of selected bifidobacteria strains may have a particular application in the elderly especially in terms of immunomodulation.