Age‐related changes in uptake and release on l‐[³H]noradrenaline in brain slices of senescence accelerated mouse

Abstract

High K+ and N-methyl-D-aspartate (NMDA) evoked L-[3H]noradrenaline (NA) release to a similar degree in the brain slices of 1-month-old senescence-accelerated resistant mice (SAM-R/1) and senescence-accelerated prone mice (SAM-P/8). However, 30 mM KCl-induced L-[3H]NA release significantly diminished in SAM-P/8 from 3 to 12 months without changing in SAM-R/1. In addition, NMDA-induced L-[3H]NA release was also reduced at 3 months and lowered to a level of spontaneous release at 12 months in SAM-P/8, but no age-related changes in SAM-R/1 were observed. It is suggested that NA release from NA nerve terminals responsive to depolarization is reduced in SAM-P/8 at an earlier stage than in SAM-R/1. Furthermore, NMDA receptors which could be localized in the soma and/or nerve terminals, seem to be involved in NA release and to be decreased with advancing age in SAM-P/8.

Senescence-Accelerated Mouse (SAM) with Special References to Neurodegeneration Models, SAMP8 and SAMP10 Mice

“…Biochemical studies done by Nomura and his colleagues demonstrated that there was an age-associated reduction in K ? -or NMDA-evoked release of noradrena1in and an increase in a 2 receptors in the brain of SAMP8 [22,23]. From these results, Miyamoto suggested that the deterioration in the noradrenergic system may participate in reduced anxiety-like behavior [15].…”

“…Cerebral cortical [ 3 H]MK-801 binding for N-methyl-D-aspartate (NMDA) receptor/channels in the SAMP8 mouse was lower than that in the SAMR1 mouse, indicating that NMDA receptor functions seem to be deficient in neurons of the SAMP8 mouse brain [51]. NMDA-induced release of [ 3 H]acetylcholine (ACh) and [ 3 H]noradrenaline (NA) was markedly reduced in the brains of SAMP8 mice [23,52]. Since NMDA receptor/ channels are found on both soma and terminals of ACh and NA-containing neurons, these results in the brains of SAMP8 mice strongly suggest functional deterioration of glutamatergic, cholinergic, and noradrenergic neurotransmission in the SAMP8 brain [53].…”

Age-related changes in the brains of senescence-accelerated mice (SAM): Association with glial and endothelial reactions

“…This morphological analysis was followed by a series of studies focusing on alterations of the cell membrane or on the numbers of neurotransmitter receptors (binding sites) (Flood et al, 1992(Flood et al, , 1993Kitamura et al, 1989Kitamura et al, , 1992Nomura et al, 1996Nomura et al, , 1997Zhao and Nomura, 1990;Zhao et al, 1992). Age-related changes were found in receptors for N-methyl-D-aspartate (NMDA), acetylcholine (M 1 ), serotonin, dopamine, opioids, and ␥-aminobutyric acid (GABA), as well as in ␣-adrenoreceptors.…”

Senescence-Accelerated Mice P8: A Tool to Study Brain Aging and Alzheimer's Disease in a Mouse Model

“…SAMP8 presented not only similar characteristics to aged humans, such as shorter lifespan, lordosis, reduced physical activity, and hair loss [46,47], but also some neurodegenerative features, such as early onset of learning and memory deficits [48], altered emotions and abnormal circadian rhythm [49,50], neuronal cell loss [51], and reduction in the release of neurotransmitters in the brain [52,53]. Besides, impairment of mitochondrial functions has been shown in SAMP8 brain at a relatively early age compared to SAMR1 mice [29].…”