In the present study the effects of long-term treatment with the 1,4-dihydropyridine calcium antagonist nimodipine on ultrastructural alterations of the microvascular morphology were examined in the frontoparietal cortex, entorhinal cortex and CA1 of the hippocampus in the aged rat. Qualitative observations of cerebral microvasculature of aged (30 months) Wistar rats revealed the presence of microvascular fibrosis, membranous inclusions within the basement membrane and basement membrane thickenings. In several cortical regions the percentage of aberrant microvessels was significantly reduced in the nimodipine-treated rats. The observed microvascular anomalies were classified into five distinct categories of which microvascular fibrosis type II, defined as collagen deposits up to 1 micron within the microvascular basement membrane, showed the strongest reduction in the nimodipine-treated cases. The decrement of the percentage of aberrant microvessels and the relative occurrence of several classes of microvascular deviations showed some variation in the various brain regions examined and was most pronounced in frontoparietal cortex layer III. These results may provide a morphological basis for the improved motor and cognitive performance in aged rats after long-term oral nimodipine administration.

Aging↗

PubMedDate not supplied

Beneficial effect of nimodipine on peripheral nerve function in aged rats.

In aged rats neuromuscular function and motor coordination is gradually impaired. Major motor deficits were seen in rats of more than 2 years of age; with increasing age, the incidence of abnormal footprints increased sharply. Oral nimodipine, a Ca2(+)-entry blocker of the dihydropyridine type, treatment suppressed and/or delayed the appearance of these abnormal footprints. In aged rats that already displayed a considerable amount of abnormal footprints in the free walking pattern, oral nimodipine treatment was similarly effective. Nimodipine not only delays the onset of age-related motor deficits, but also may counteract these deficits once already present. In aged rats the nerve conduction velocities were severely diminished. Nimodipine treatment resulted in an enhancement of the sciatic and caudal nerve conduction velocities. Histological analysis revealed a lower fiber density in aged rats compared to aged nimodipine-treated rats. Whether nimodipine acts directly on the peripheral nervous system is currently unclear. Nevertheless, the present study lends further support for the beneficial effects of nimodipine in age-related motor deficits in the rat.

Administration, Oral↗

PubMedDate not supplied

Expression of alpha 4-1 and alpha 5 nicotinic cholinoceptor mRNA in the aging rat cerebral cortex.

Although important in neurodegeneration, systematic studies of nicotinic acetylcholine receptor expression in normal aging human brains are difficult to perform. We have studied the expression of nicotinic receptor alpha 4-1 and alpha 5 mRNA in the frontal and parietal isocortex of 3- (young adult), 24- (late middle aged), and 33-month-old (old) rats by nonisotopic in situ hybridization. In all groups transcripts were mainly present in layer II/III and V pyramidal neurons. The numerical densities of alpha 4-1 mRNA-containing neurons with respect to those of cresyl violet-stained neurons decreased with aging in the rat frontal and parietal cortex, while those of alpha 5 mRNA-containing neurons were not affected. These findings point to an age-related decrease of the percentages of numerical densities of alpha 4-1 mRNA-containing neurons, which has to be taken into account as a possible substrate for the well-known decrease of nicotine binding sites in the aging cerebral cortex.

Aging↗

PubMedDate not supplied

[The presynaptic metabolic modulation of the impulse-dependent release of 3H-serotonin from rat brain slices by ipsapirone (TVX Q 7821) and other serotonin agonists].

The experiments with thin slices of the cortex and dorsal raphe nucleus of rat midbrain which were incubated with [3H]-hydroxytryptamine ([3H-]HT) have established that serotonin and its agonists inhibit 3H-HT release from the electrically stimulated slices. The serotonin agonists ipsapirone (TVX Q 7821), buspirone, gepirone, and 8-OH-DPAT which mainly stimulate the Type 1A serotonin receptors of somatodendritic synapses inhibit the release of [3H]-HT from the dorsal raphe nucleus slices to a greater extent rather from those of the cortex. On the contrary, the serotonin agonists TFMPP, mCPP, and Ru 24969 which predominantly affect 1B-HT receptors largely inhibit [3H]-HT release from the electrically stimulated cortical slices. Ipsapirone-induced inhibition of the impulse-dependent release of [3H]-HT has been found to be associated with changes in intracellular cAMP levels and protein kinase activity. The nature of serotonin agonist-induced modulation of the impulse-dependent release of [3H]-HT from serotoninergic neurons is discussed in the paper.

Animals↗