Tyrosine hydroxylase-like immunoreactivity and catecholamine fluorescence in ciliary ganglion neurons

In the ciliary ganglia of monkeys, dogs, cats and rats, some neuronal perikarya exhibited tyrosine hydroxylase-like immunoreactivity; neither dopamine-beta-hydroxylase-like immunoreactivity nor phenylethanolamine-N-methyltransferase-like immunoreactivity was found in perikarya. Some perikarya of ciliary ganglion neurons displayed catecholamine fluorescence; the fluorescent perikarya were significantly increased in number in dogs injected with nialamide. Thus the existence of dopamine-containing ciliary ganglion neurons was suggested.     

Age-related changes in noradrenergic sympathetic innervation of the rat spleen is strain dependent

Previous findings from our laboratory revealed an age-related decline in noradrenergic (NA) sympathetic innervation of the spleen in male Fischer 344 (F344) rats. The purpose of this study was to determine whether other rat strains also progressively lose NA sympathetic nerves in the aging spleen. Sympathetic innervation of spleens from 3- and 21-month-old male F344, Brown Norway (BN), BN X F344 (BNF(1)), and Lewis rats was examined using fluorescence histochemistry to localize catecholamines combined with morphometric analysis and using high-performance liquid chromatography with electrochemical detection for measuring norepinephrine (NE). Neurochemistry revealed a significant age-related decline in NE concentrations in spleens from F344 and Lewis rats. In contrast, there was no effect of age on splenic NE concentrations in BN or BNF(1) rats. Consistent with neurochemical analysis, fluorescence histochemistry revealed a striking decline in NA innervation of spleens from old F344 and Lewis rats not observed in the other two strains. However, in BN and BNF(1) rats, nerve fibers were diminished in distal portions of the spleen but not in the hilar regions. Morphometric analysis confirmed neurochemical and histological findings, revealing approximately 65-70% loss in NA nerve density in spleens from F344 and Lewis rats. These findings indicate that age-related changes in sympathetic innervation of the rat spleen are strain-dependent. Whether the loss of sympathetic nerves in spleens from F344 and Lewis rats is associated with age-related changes in the splenic microenvironment remains to be determined. The functional significance of altered sympathetic innervation of the spleen with advancing age is discussed.     

Enhanced effects of 6-hydroxydopamine on evoked overflow of striatal dopamine in aged rats

Nigrostriatal dopamine neurons degenerate during aging, and the excessive loss of dopamine neurons that occurs with Parkinson's disease is usually confined to older individuals. Although 6-hydroxydopamine lesioning of the nigrostriatal dopamine system is a common method for producing animal models of dopamine neuron degeneration, there have been relatively few studies that have examined the effects of 6-hydroxydopamine on the dopamine systems of aged animals. The present experiments were designed to determine if nigrostriatal dopamine neurons in aged rats are more sensitive to the neurotoxic effects of 6-hydroxydopamine than those of younger rats. Young (4-month-old), middle-aged (14-month-old) and aged (24-month-old) Fischer-344 rats were given a single injection of vehicle, 50 or 100 microg 6-hydroxydopamine into the right lateral ventricle. Three to four weeks later in vivo electrochemistry was used to measure potassium-evoked overflow of dopamine in the striatum. In the young rats the 50-microg dose had no significant effect on evoked overflow of dopamine in the striatum or on post-mortem levels of dopamine in the striatum or substantia nigra. The higher dose in the young animals diminished evoked overflow of dopamine as well as tissue levels of dopamine. In the aged rats both doses of 6-hydroxydopamine led to significant decreases in evoked overflow of striatal dopamine and in tissue levels of dopamine in the striatum and substantia nigra. These results suggest that dopamine neurons of aged Fischer-344 rats are more susceptible to the toxic effects of 6-hydroxydopamine than those of younger animals.     

Glial gene expression during aging in rat striatum and in long-term responses to 6-OHDA lesions

The male rat striatum was examined for age-related changes in mRNAs expressed in astrocytes and microglia in two rat genotypes that differ by 35% in mean and maximum life spans: F344 and the longer-lived F1 (BN x F344) hybrid. The findings extend the established age-related increases in GFAP (glial fibrillary acidic protein) to other glial mRNAs: two lipoprotein mRNAs that are predominantly expressed in striatal astrocytes, apoE (apolipoprotein E) and apoJ (apolipoprotein J, clusterin, CLI, or SGP-2), and two mRNAs expressed in striatal microglia, TGF-beta1 and complement C1qB. By Northern blot hybridization, both genotypes showed progressive increases of GFAP mRNA to > 2.5-fold by the lifespan. Although the rat strains differed 35% in life span, the slope of the GFAP mRNA regression on age did not differ. Relative to GFAP, the increases of apoE, apoJ, C1q, and TGF-beta1 mRNAs were smaller, < or = 1.5-fold. Because prior studies showed that acute damage to striatal afferents induced astrocyte gene expression increases resembling those that also occur during aging, we examined long-term effects of damage to substantia nigra neurons on striatal astrocyte changes during aging. Young F344 rats were given 6-OHDA lesions that cause striatal dopamine deficits and induce GFAP. When examined 15 months later at age 18 months, there was no effect during prior lesions on the age-related elevation of GFAP mRNA. We conclude that aging changes in striatal GFAP mRNAs do not interact with loss of dopaminergic output to the striatum from 6-OHDA lesions and may be independent of the relatively modest dopaminergic losses during normal aging.     

Extracellular glutamate levels increase with age in the lateral striatum: Potential involvement of presynaptic D-2 receptors

In the lateral striatum of aged rats, dopamine D-2 receptor density is reduced and glutamate tissue content is elevated. D-2 receptor agonists have been shown to inhibit stimulated glutamate release. In the present study, microdialysis was used to investigate a potential role for D-2 receptors in the modulation of striatal glutamate efflux from 4-, 12-, 18-, and 24–26-month-old Fischer 344 rats. Extracellular basal glutamate concentrations significantly increased as a function of age in the lateral, but not medial, striatum. Neither the D-2 agonist, LY 163502, nor the D-2 antagonist, sulpiride, influenced basal glutamate efflux, suggesting that the dopaminergic system is not involved in the observed age-related increase in extracellular basal glutamate levels. In contrast to basal efflux, potassium-evoked glutamate release was not altered with age. However, LY 163502 significantly inhibited stimulated glutamate release in 4-month-old rats. This inhibitory action was not observed at any other age. Sulpiride alone did not alter stimulated glutamate release, but it did block the inhibitory effect of LY 163502 in the 4-month-old rats. These results provide in vivo evidence for an age-related functional loss in the modulation of striatal glutamate release by dopamine D-2 receptors in addition to increased basal glutamate efflux, which is not related to D-2 receptor modulation. Such mechanisms could be important in the pathophysiology of striatal cell death during aging and age-related neurodegenerative diseases. © 1993 Wiley-Liss, Inc.     

Normal and drug-induced locomotor behavior in aging: comparison to evoked DA release and tissue content in Fischer 344 rats

The consequences of aging on dopamine (DA) regulation within the nigrostriatal and mesolimbic systems were investigated with a combination of behavioral, in vivo electrochemical, and high-performance liquid chromatography measurements using 6-, 12-, 18- and 24-month old male Fischer 344 (F344) rats. Spontaneous locomotor testing demonstrated that aged (18- and 24-month) rats moved significantly less and at a slower speed than younger (6- and 12-month) animals. Additionally, systemic injection (intraperitoneal) of the DA uptake inhibitor, nomifensine, was significantly less efficacious in augmenting the locomotor activity of aged rats compared to the younger animals. Age-dependent alterations in the release capacity of DA neurons within the regions involved in movement were investigated using in vivo electrochemistry. These recordings indicated that both the magnitude and temporal dynamics of potassium (70 mM)-evoked DA overflow were affected by the aging process. Signal amplitudes recorded in the 24-month rats were 30–60% reduced in both the striatum and nucleus accumbens as compared to the young adult groups. In addition, the duration of the electrochemical DA signals recorded within the striatum of 24-month old rats was twice that in the younger animals (6- and 12-month). Whole tissue measurements of DA and DA metabolites suggest age-related deficits in locomotion and DA release were not related to decreases in the storage or synthesis of DA within the striatum, nucleus accumbens, substantia nigra, ventral tegmental area or medial prefrontal cortex. Taken together, these results indicate age-dependent deficits in movement are related to the dynamic properties of DA release and not static measures of DA content.     

Effect of prolonged physical training on the histochemically demonstrable catecholamines in the sympathetic neurons,the adrenal gland and extra-adrenal catecholamine storing cells of the rat

The effect of daily physical training for 24 months on the sympathetic neurons, adrenal gland, extra-adrenal catecholamine storing cells and on the heart was investigated in rats. The tissue catecholamine fluorescence intensity was determined by microfluorimetric quantitation of catecholamines. The maximal and final body weights were significantly lower in trained animals. The trained rats showed prominent increase of heart weight relative to body weight, while the adrenals did not enlarge. The adrenergic nerve fiber density of the heart and the fluorescence intensity of the terminal axons were significantly increased. There were no changes in the fluorescence intensity of the perikarya of the sympathetic neurons and the amount of extra-adrenal catecholamine storing cells after physical exercise. The volume of the superior cervical ganglion was doubled and the neuronal perikarya were enlarged in trained animals. The prolonged physical training throughout the life span of the rat gave new information about the reactions of the sympathetic nervous system to physical exercise.     

Transplantation of norepinephrine neurons into aged rats improves performance of a learned task

A reproducible behavioral correlate of aging in rodents is deficient performance of inhibitory avoidance memory tasks. Impaired performance has been attributed, in part, to age-related changes in brain norepinephrine (NE) system function. To determine whether supplementation of brain NE can ameliorate avoidance deficits in aged animals, we transplanted noradrenergic locus coeruleus neurons from fetal rat donors into the third cerebral ventricle of 24-month-old male F344 rats. Aged rats that received NE-containing grafts exhibited significant improvement of inhibitory avoidance retention performance compared to both unoperated aged animals and aged animals that received grafts of cerebellar tissue. Improved behavioral performance was prevented by pretreatment of NE graft recipients with the beta-adrenergic receptor blocking agent, propranolol, and was mimicked by chronic intraventricular infusion of NE. Taken together, our findings support the view that age-related declines in brain NE content contribute to age-related deficits in inhibitory avoidance performance, and that NE replacement therapy can improve performance of this task in aged rats.     

Selective reduction of glucocorticoid receptor immunoreactivity in the hippocampal formation and central amygdaloid nucleus of the aged rat.

Hippocampal cell loss during aging has been related to the toxic effects of corticosterone on this cell population. It is not known which receptor mediates corticosterone cytotoxicity. At least two types of receptors for corticosterone have been recognized in the rat brain, type I (corticosterone preferring receptor, CR) and type II (glucocorticoid receptor, GR). In the present study the possible changes in GR immunoreactivity (IR) in various tel- and diencephalic regions of the aged rat have been investigated using immunocytochemistry coupled with computer-assisted image analysis. Male Sprague-Dawley rats of 3, 12 and 24 months of age were used (n = 5/group). A selective decrease of GR-IR was observed in the CA1 hippocampal field and central amygdaloid nucleus of the 24-month-old with respect to both 3- and 12-month-old rats. While in the former region GR-IR decrease was paralleled by a decrease of IR field area, no age-related decrease of GR-IR profile number was detected in central amygdaloid nucleus. A significant decrease of GR-IR and IR field area was also observed in the dentate gyrus of 24- vs 12-month-old rats but not vs 3-month-old rats. The analysis of adjacent sections stained with Cresyl violet showed a pattern of age-related changes (decrease of neuronal profiles in CA1 field pyramidal layer and dentate gyrus granular layer, and no change in the central amygdaloid nucleus of aged rats) which paralleled the observed changes in GR-IR in the same areas. This study provides evidence that GR are selectively decreased in the hippocampal formation and in the central amygdaloid nucleus of the aged rat.(ABSTRACT TRUNCATED AT 250 WORDS)     

Region-specific decline in the expression of metabotropic glutamate receptor 7 mRNA in rat brain during aging

Age-dependent changes in the expression of group III metabotropic glutamate receptors (mGluR4 and mGluR7) were studied by quantitative in situ hybridization using male Fisher 344 rats 3, 12 and 25 months of age. Results indicate an early decrease in mGluR7 mRNA level in several cortical areas including the frontal, parietal and temporal cortices. In the hippocampus, mGluR7 mRNA levels decreased in the CA1 region and the lower blade of the dentate gyrus. Moreover, significant decrease was found in the laterodorsal thalamic nucleus at 12 months of age. Other regions such as the caudate putamen and nucleus accumbens showed no age-related changes in mGluR7 mRNA levels. Analysis of emulsion autoradiograms revealed a 36% decrease of mGluR7 mRNA in Purkinje neurons in the 12-month-old group and a 48% decline in the 25-month-old group as compared to the 3-month-old group. A substantial decrease in mGluR4 mRNA level was found in the granule cell layer of the cerebellum during aging. The difference between the young and aged groups exceeded 35%. These region-specific decreases may have important implication in some of the age-related changes in cognitive, motor and/or sensory functions.     

Reduced calcium uptake by rat brain mitochondria and synaptosomes in response to aging

Synaptosomes were isolated from cerebral cortex of 3-, 18- and 24-month-old male, Fisher 344 rats and 45Ca2+ uptake was measured at 1, 3, 5, 15 and 30 s time periods following 65 mM KCl depolarization. Identical experiments were performed in which 5 mM KCl was added to examine age-related changes in resting 45Ca2+ accumulation by synaptosomes. Both 'fast-' and 'slow-phase' voltage-dependent 45Ca2+ uptake were significantly reduced in synaptosomes from 18- and 24- vs 3-month-old rats. No age-related change in resting (5 mM KCl) 45Ca2+ accumulation was observed. ATP-dependent and respiration-linked 45Ca2+ uptake was examined in mitochondria isolated from whole brains of 3- and 28-month-old male, hooded Long-Evans rats. Both ATP-dependent and glutamate-malate-ADP stimulated 45Ca2+ uptake by mitochondria were markedly reduced in response to aging. Respiratory control ratios were the same for 3- and 28-month-old mitochondria, suggesting that the decrement in 45Ca2+ uptake was not caused by an age-related decline in respiratory activity of mitochondria. The results of this study show that both voltage-dependent calcium entry into presynaptic nerve terminals and calcium uptake by mitochondria in brain decline with advanced aging. Age-related changes in cytosolic calcium levels could underlie, at least in part, cellular decrements in brain observed with aging.     

Age-related changes in the Purkinje's cells in the rat cerebellar cortex: a quantitative electron microscopic study

The present study was undertaken to assess age-related changes in the Purkinje's cells in the rat cerebellar cortex. The cellular and nucleolar volumes and the volume percentage of lipofuscin per cytoplasma were measured in six age groups. The number of Purkinje's cells was also counted. The cellular volume of rats aged 18, 24 and 30 months decreased significantly as compared with that of 3-month-old rats. The nucleolar volume of rats aged 12, 18, 24 and 30 months decreased significantly as compared with that of 3-month-old rats. The accumulation of lipofuscin in the cytoplasma of the Purkinje's cells was observed more or less in all ages. The degree of accumulation of lipofuscin in the Purkinje's cells increased with aging. The number of Purkinje's cells at the ages of 24 and 30 months decreased significantly as compared with that of 3-month-old rats.     

Aging is neuroprotective during global ischemia but leads to increased caspase-3 and apoptotic activity in hippocampal neurons

Previously, we found a significantly greater number of surviving CA1 neurons to global ischemia in the aged (24-month-old) F344 rats than in young (4-month-old) rats. The present study tests the hypothesis that aging retards neuronal death in the hippocampal CA1 region following cerebral ischemia. The CA1 "living cell ratio" was significantly greater in aged than in young rats at three days (62+/-8% vs. 30+/-8%) and at eight days (36+/-6% vs. 17+/-5%), but not at 14 days (15+/-12% vs. 18+/-12%) following ischemia. The number of the CA1 cells exhibiting co-localized TdT-mediated X-dUTP nick end labeling reaction and caspase-3 active peptide (C3AP) immunoreactivity was greater in aged than young animals at three and eight days following ischemia (36+/-8/mm vs. 3+/-1/mm and 36+/-14 vs. 0+/-0, p<0.05 respectively). Also, the total number of C3AP-positive cells in the CA1 region in the aged group was significantly greater than in the young group at three and eight days post-ischemia (p<0.05). Aging appears to delay caspase-3-dependent apoptotic cell death induced by global ischemia in the CA1 region of the hippocampus, consistent with an age-induced neuroprotective process.     

Selective changes in the contents of noradrenaline, dopamine and serotonin in rat brain areas during aging

This study examines the age-associated changes in noradrenaline (NA), dopamine (DA), 3,4-dihydroxyphenyl-acetic acid (DOPAC), serotonin (5-HT) and 5-hydroxy-3-indoleacetic acid (5-HIAA) in different brain areas of rats. DA and DOPAC concentrations in striatum increased at third month of age, remaining without significant variations until 12th month of age, and decreasing in 24-month-old rats. DA concentration dropped in hippocampus, amygdala and brainstem of 24-month-old-rats, whereas DOPAC levels decreased only in hippocampus. These changes suggest an age-dependent deficit of the dopaminergic system, presumably related to a reduced number/activity of DA nigrostriatal and mesolimbic neurons. An age-induced decline in NA content was found in the pons-medulla, the area containing NA neuronal bodies. Concentrations of 5-HT were reduced with aging in frontal cortex, showing a tendency to decrease in all brain areas examined. The increased 5-HIAA/5-HT ratio found in frontal cortex, amygdala and striatum suggests an age-related decreased synthesis and an accelerated 5-HT metabolism. The 5-HIAA content decreased in brainstem of the oldest rats. These findings point to a selective impairment of nigrostriatal and mesolimbic DA in aging rats, whereas reductions in NA were restricted to cell bodies region and 5-HT showed changes of different extent in areas of terminals and neuronal cell bodies.     

Relationship between catecholamine neurons and cerebral blood vessels studied by their simultaneous fluorescent revelation in the rat brainstem

In order to study the relationship between catecholamine neurons and cerebral blood vessels, a technique was developed which permitted the simultaneous visualization of blue-green fluorescent catecholamine neurons and red fluorescent stained blood vessels in the brain of the normal rat. Sympathetic nerve fibers were found on the major arteries and in the pia-arachnoid at the base of the brainstem and also along paramedial and lateral perforating arteries as small as 10–12 μm within the brain. Running within the parenchyma, central catecholamine nerve fibers occasionally approached and intersected smaller blood vessels, either arterioles or venules of 8–12 μm, and infrequently climbed along or encircled these vessels for a limited distance, particularly within the lateral tegmentum. Across the nuclei of the brainstem, no overall contiguity of catecholamine terminals with capillaries was apparent, and no correlation between the density of catecholamine varicosities and that of capillaries existed. Only in regions with a high density of both catecholamine varicosities and capillaries, such as in the principal olivary nucleus, did a significant overlap of the two occur. But in most cases of moderately to densely innervated and vascularized regions, such as the solitary tract nuclei, the greatest concentration of terminals appeared over the parenchyma. Regarding the blood supply to the catecholamine neurons, their perikarya did not receive a particularly dense capillary supply relative to other nuclei. However, a special relationship of catecholamine cells to blood vessels was suggested, particularly in the case of dopamine neurons in the substantia nigra by the close apposition of cellular processes to adjacent small vessels. This morphological study was undertaken to determine whether central catecholamine neurons may significantly innervate cerebral blood vessels and accordingly, may function analogously to the peripheral sympathetic adrenergic neurons in the regulation of the vascular system. Although a limited number of associations between central catecholamine nerve terminals and small blood vessels suggested the possibility of an innervation in a few regions, the lack of an overall correspondence and correlation between the two across brainstem nuclei indicated that the analogy of central catecholamine neurons to the sympathetic nervous system was inappropriate. On the other hand, evidence of contact with vessels by presumed dendrites of the catecholamine neurons suggested a possible vascular sensory function.     

Impact of very old age on hypothalamic dopaminergic neurons in the female rat: a morphometric study

Dopaminergic neurons of the A(12) (tuberoinfundibular dopaminergic system) and A(14) (periventricular dopaminergic system) hypothalamic areas exert a tonic inhibitory control of prolactin secretion. Tuberoinfundibular dopaminergic system neuron function is known to decline during aging in rats, but little is known about the impact of extreme age on neuron number and morphology in the two systems. We morphometrically assessed the neurons of the tuberoinfundibular dopaminergic system and the periventricular dopaminergic system in female rats 6 (young, Y), 24 (old, O), and 30-32 (senescent, S) months old. Serial coronal sections of fixed hypothalami were immunohistochemically labeled for tyrosine hydroxylase, and immunoreactive perikarya from the A(12) and A(14) areas were quantitatively characterized and compared among the three age groups. Radioimmunoassay was used to measure serum prolactin. The number of A(12) tyrosine hydroxylase-immunoreactive perikarya showed a steady decline with age, whereas the number of A(14) tyrosine hydroxylase-immunoreactive perikarya remained stable from young to old age but showed a sharp drop in the senescent rats. In the old rats, tyrosine hydroxylase-immunoreactive neuronal area (A(12) = 135.37 and A(14) = 158.79 microm(2)) was significantly higher than that of young (A(12) = 72.56 and A(14) = 99.7 microm(2)) and senescent animals (A(12) = 95.5 and A(14) = 106.5 microm(2)). Densitometric assessment of median eminence tyrosine hydroxylase immunoreactivity revealed a steady age-related reduction of tyrosine hydroxylase content in the median eminence. Serum prolactin levels increased steadily with age. We conclude that, in the female rat, aging brings about a progressive loss of both tuberoinfundibular dopaminergic system and periventricular dopaminergic system neurons, which becomes more conspicuous at extreme ages.     

Involvement of catecholaminergic nerve fibers in angiotensin II-induced drinking in the Japanese quail, Coturnix coturnix japonica

Monamine distribution in a septohypothalamic area was investigated in the Japanese quail using a histochemical fluorescence method. This area includes the subfornical organ (SFO) and the preoptic area (POA) which are inferred dipsogenic receptor sites for angiotensin II (AII) in the Japanese quail. Nerve fibers showing yellow-green fluorescence were found between the POA and the SFO. Thwy traversed from the POA to the SFO, and some fibers seemed to terminate on the neurons in the SFO. After a low dose of reserpine, a considerable number of fluorescent perikarya were found in the POA. These fibers and perikarya appeared to be of primary catecholamine judging from the fluorescence color. Following transection of these fibers, fluorescence disappeared from the fibers located on the SFO side of the transection plane, while it became a little more intense on the POA side. After transection, microinjection of AII into the POA was no longer effective in induction of drinking. On the other hand, sham operation or transection in areas other than between the POA and the SFO produced only minute changes in those fluorescent fibers and had little effect on the dipsogenic potency of AII injected into the POA. These results suggest that information of AII perceived at the POA is transferred to the SFO via those primary catecholamine-containing nerve fibers, which effect induced drinking.     

How does prolonged caloric restriction ameliorate age-related impairment of long-term potentiation in the hippocampus?

Prolonged dietary restriction has been reported to suppress age-induced phenomena. In order to investigate how prolonged caloric restriction reduces age-related deterioration of hippocampal synaptic transmission, we compared the levels of major hippocampal polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid between 4- and 26-month-old rats. The Ca(2+) responses upon perfusion of NMDA or 30 mM K(+) between 4- and 26-month-old rats with prolonged dietary restriction were also compared using the fluorescent probe Fura-2. A decrease in membrane arachidonic acid is thought to be a major causal factor in the age-related impairment of long-term potentiation. Long-term caloric restriction seems to increase arachidonic acid levels regardless of age. However, there is no significant difference of hippocampal arachidonic acid levels between in freely feeding 4- and 26-month-old rats. Similar results were obtained from the measurement of hippocampal docosahexaenoic acid levels. Under caloric restriction, the 500 microM N-methyl-D-aspartate-induced Ca(2+) response was greatly reduced by aging, while the 30 mM K(+)-induced Ca(2+) response was not affected. In our preliminary data, the amplitude of the population spike after tetanic stimulation did not differ between 4- and 26-month-old rats under caloric restriction, while 50 microM of 2-amino-5-phosphonovaleric acid, a N-methyl-D-aspartate antagonist, markedly inhibited a potentiation of the population spike in 4-month-old rats, but with negligible inhibition in 26-month-old rats. From these results, an age-related impairment of hippocampal excitatory synaptic transmission may not be solely due to the reduction of membrane arachidonic acid. Caloric restriction might prevent age-related reduction in hippocampal synaptic transmission by enhancing non-N-methyl-D-aspartate mechanisms.     

Age-related changes in the antioxidative potential of cerebral microvessels

To determine if aging in rats is associated with increased susceptibility of cerebral microvessels to oxidative damage microvessels from the cerebrum of 4-, 12-, 18- and 26-month-old male Fischer 344 rats were studied. The malondialdehyde (MDA) (μg/mg protein) content of cerebral microvessels from 12-month-old rats (0.032 ± 0.002) was significantly higher than that in 4-month-old rats (0.020 ± 0.015) P < 0.01. The difference between 26-month-old (0.025 ± 0.002) and 4-month-old rats did not reach statistical significance. The antioxidative potential was measured in the presence of a peroxy radical generator 2,2′-azobis(2-amidionopropane)hydrochloride (AAPH) with monitoring of the fluorescence of phycoerythrin at 37°C. The free radical quenching activity of cerebral microvessels expressed as % inhibition of phycoerythrin oxidation by AAPH was significantly reduced in 12-month-old (33.6 ± 4.6%) and 18-month-old rats (26.9 ± 1.4%) compared with 4-month-old rats (54.3 ± 4.9%) (P < 0.01). The 26-month-old rats (46.4 ± 4.6%) were not significantly different from 4-month-old rats. It is concluded that aging is associated with increased lipid peroxidation byproducts in cerebral microvessels along with a transient decrease in their antioxidative capacity.