Immunocytochemical study of catecholaminergic neurons in the senescence-accelerated mouse (SAM-P8) brain

Abstract

The catecholaminergic neurons of senescence-accelerated mice (SAM-P8) were analyzed by immunohistochemical microphotometry in terms of immunoreactivities to aromatic L-amino acid decarboxylase (AADC), dopamine (DA), or noradrenaline (NA). Accelerated senescence-resistant mice (SAM-R1) were used as control mice. The immunoreactivities to AADC, DA, and NA of the catecholaminergic neurons of the SAM-P8 mice were weaker than those of the SAM-R1 mice in all the brain regions. Immunoelectron microscopy revealed progressive degeneration of dopaminergic neurons and their terminal fibers in the substantia nigra as well as in noradrenergic neurons and their proximal dendrites in the locus coeruleus of the SAM-P8 mice. In contrast, there was no difference between the SAM-P8 and SAM-R1 mice in the distribution of AADC-only positive neurons (designated as D neurons in the rat brain by Jaeger et al.) nor in their immunoreactivities. These results may indicate that DA neurons in the substantia nigra and NA neurons in the locus coeruleus degenarate more rapidly during aging in SAM-P8 mice than in control SAM-R1 mice and that D neurons may function as a part of a compensatory system for the decreases in catecholaminergic neurons during aging.

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

“…Recently, Zhu et al [45] revealed using the methods of histological silver staining and TUNEL that some Purkinje cells in the medial cerebellum and the vermis appeared to disappear during aging in SAMP8 mice, consistent with the findings in Alzheimer brains [46,47] . d. Other findings: In addition, an immunohistochemical study by Karasawa et al revealed that dopamine neurons in the substantia nigra and noradrenaline neurons in the locus coeruleus degenerated more rapidly during aging in SAMP8 mice than in control SAMR1 mice [48]. On the other hand, Tanaka et al [49] investigated the changes in oligodendrocytes in the brains of SAMP8 mice using immunohistochemistry for myelin basic protein (MBP) and 2 0 3 0 -cyclic nucleotide 3 0 -phosphodiesterase (CNP) as the oligodendrocyte markers.…”

Sensitivity of Serotonin Synthesis to Synthesis Inhibitor GTP Cyclohydrolase I in Senescence-Accelerated Mouse-Prone Inbred Strain (SAMP8)

“…Reports on 5-HT neurons have described the regional specificity of degeneration [6,17]. We have previously reported decrease in IR-Is and morphological change to DA neurons in aged SAMP8 [4] and noted the sensitivity of DA neurons to an inhibitor of monoamine synthesis. Tetrahydrobiopterin (BH4) is a coenzyme of both TH and tryptophan hydroxylase (TrH), the rate-limiting enzymes in catecholamine and indolamine syntheses, respectively.…”

“…We have previously reported decreased immunoreactive intensity (IR-Is) and morphological changes in dopaminergic (DA) neurons in senescenceaccelerated mouse-prone (SAMP8) mice [4]. Regarding the changes in monoamine synthesis in relation to aging, we have also reported the sensitivity of CA neurons to inhibitor of monoamine synthesis [5].…”

Modulation of Signal Transduction Pathways in Senescence-Accelerated Mice P8 Strain: A Useful Tool for Alzheimer’s Disease Research

“…However, there is a decrease in the number of dopamine (DA) neurons and the associated ultrastructural changes in the neurons of the nigrostriatal system in SAMP8 as compared with SAMR1. This reduction is even greater in aged SAMP8 mice (8-10 months old) (Karasawa et al, 1997), suggesting a reduced DA level in SAMP8 worsened by age. The administration of 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, to inhibit DA and serotonin syntheses in young mice (2 months old) and aged mice (10 months old), revealed that DA turnover is lower in aged mice than in young mice (Karasawa et al, 1999).…”