Protection by prosaposin against ischemia-induced learning disability and neuronal loss

Sano, Akira; Matsuda, Seiji; Wen, Tong-Chun; Kotani, Yasunori; Kondoh, Keiji; Ueno, Shu‐ichi; Kakimoto, Yasuo; Yoshimura, Hidetoshi; Sakanaka, Masahiro

doi:10.1016/0921-8696(94)92683-2

Cited by 16 publications

(25 citation statements)

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“…In a similar way, saposin C itself was shown to prevent apoptosis in prostate cancer cells [128]. These effects are consistent with the observations that prosaposin addition rescues neuroblastoma cells, primary hippocampal neurons [129], Schwann cells [125], and PC12 pheochromocytoma cells [119] from apoptosis induced by various agens. Neurotrophic, neuroregenerative and anti-apoptotic effects of prosaposin are apparently mediated by modification of signaling pathways and prosaposin was shown to be involved in ERK phosphorylation [130].…”

Section: Prosaposin Is a Potential Catalyst Of Ganglioside Shedding Asupporting

confidence: 77%

Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Lauc

Heffer-Lauc

2006

Biochimica et Biophysica Acta (BBA) - General Subjects

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Section: Prosaposin Is a Potential Catalyst Of Ganglioside Shedding Asupporting

confidence: 77%

Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Lauc

Heffer-Lauc

2006

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…The CA1 region in particular is one of the most important areas for cognitive function and is noted for its susceptibility to ischemia. 21,22 Sakanaka and colleagues 23 have demonstrated that a relationship exists between the latency of the passive avoidance task and the cell density of the CA1 region. Our results for the cerebral function and morphological changes of the brain are in accordance with the previous studies.…”

Section: Parameters Indicating Renal Functionmentioning

confidence: 99%

“…Our results for the cerebral function and morphological changes of the brain are in accordance with the previous studies. [21][22][23] This structural difference in the vascular system may explain the difference in neuronal cell preservation between the CA1 region and the deep cortex.…”

Section: Parameters Indicating Renal Functionmentioning

confidence: 99%

Long-Term Inhibition of Renin-Angiotensin System Sustains Memory Function in Aged Dahl Rats

Hirawa¹,

Uehara²,

Kawabata³

et al. 1999

Hypertension

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Abstract-The Dahl salt-sensitive (DS) rat, a genetic model of salt-induced hypertension in humans, is more likely to develop severe vascular injuries than a rat with spontaneous hypertension. We designed an experiment to scrutinize the effects of renin-angiotensin inhibition on cognitive dysfunction in the aged, normotensive DS with a passive avoidance test. Eighteen months of treatment with a very low dose of the angiotensin-converting enzyme (ACE) inhibitor cilazapril (2.5 g/mL in drinking water) or the angiotensin II type 1 receptor antagonist E4177 did not reduce blood pressure throughout the experiment, although in the low dose cilazapril group (12.5 g/mL in drinking water), blood pressure dropped within 6 months after treatment began. The cilazapril treatments dose-dependently improved memory function in the aged, normotensive DS fed a low-salt diet compared with the untreated, control rats. This improvement was associated with significant increases in hippocampal CA1 cells and capillary densities in the CA1 regions compared with those in the untreated DS. Similarly, E4177 slightly improved the memory dysfunction observed in the aged DS. The cells in the hippocampal CA1 region were restored slightly, but the capillary densities were not influenced by the receptor antagonist. On the other hand, the ACE inhibitor and receptor antagonist both attenuated urinary protein excretions with an improvement of glomerular sclerosis. These data suggest that long-term treatment with an ACE inhibitor improves memory dysfunction probably through restoration of capillary and hippocampal cells. The effects are due to the inhibition of the angiotensin II type 1 receptor and probably to the enhancement of the kallikrein-kinin system. (Hypertension. 1999;34:496-502.)Key Words: cilazapril Ⅲ angiotensin-converting enzyme inhibitors Ⅲ receptors, angiotensin Ⅲ memory Ⅲ cognition Ⅲ rats, aging Ⅲ aging R ecent advances in vascular physiology have emphasized an integration of multiple risk factors that form vascular lesions in patients with various disorders that affect the cardiovascular system. The understanding of the process of vascular lesion development has led to the establishment of pharmacological and nonpharmacological strategies for the prevention of vascular damage in hypertension, hyperlipidemia, or abnormal glucose metabolism. In addition to such acquired forms of risk factors, some inevitable factors, eg, gender, genetic loading, and aging, contribute to the progression of vascular injuries. Among these factors, aging is particularly important. The development of a therapeutic strategy for the aging population is urgently needed. In Japan, by year 2015, people Ն65 years of age will constitute 25% of the population, and worldwide, by year 2025, this population will have doubled. In addition, Ϸ50% of dementia or cognitive dysfunction in the elderly are attributable to cerebrovascular lesions. 1 The elucidation of the mechanism of cerebrovascular lesions related to the process of aging provides a useful strategy to preven...

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“…Several studies demonstrated that prosaposin prevents nerve degeneration and promotes nerve regeneration in animal models of nerve injuries, including a strong protective action against ischemic and wound stab damage of hippocampal neurons (24,30,43,54). The relative abundance of the exon 8-containing prosaposin isoform was recently shown to sharply decline following ischemia and stab wound in rat brain (19).…”

Section: Vol 25 2005 Exon 8-containing Prosaposin Gene Splice Variamentioning

confidence: 99%

“…Many functions have been attributed to the secreted form, mainly in the nervous and the reproductive systems. It is a neurotrophic and myelinotrophic factor (18,45), preventing apoptosis of neuronal cells in tissue culture (22,60), and a neuroprotective and regenerative agent in vivo (30,54).…”

mentioning

confidence: 99%

The Exon 8-Containing Prosaposin Gene Splice Variant Is Dispensable for Mouse Development, Lysosomal Function, and Secretion

Cohen¹,

Auerbach

Ravid³

et al. 2005

Molecular and Cellular Biology

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Prosaposin is a multifunctional protein with diverse functions. Intracellularly, prosaposin is a precursor of four sphingolipid activator proteins, saposins A to D, which are required for hydrolysis of sphingolipids by several lysosomal exohydrolases. Secreted prosaposin has been implicated as a neurotrophic, myelinotrophic, and myotrophic factor as well as a spermatogenic factor. It has also been implicated in fertilization. The human and the mouse prosaposin gene has a 9-bp exon (exon 8) that is alternatively spliced, resulting in an isoform with three extra amino acids, Gln-Asp-Gln, within the saposin B domain. Alternative splicing in the prosaposin gene is conserved from fish to humans, tissue specific, and regulated in the brain during development and nerve regeneration-degeneration processes. To elucidate the physiological role of alternative splicing, we have generated a mouse lacking exon 8 by homologous recombination. The exon 8 prosaposin mutant mice are healthy and fertile with no obvious phenotype. No changes were detected in prosaposin secretion or in accumulation and metabolism of gangliosides, sulfatides, neutral glycosphingolipids, neutral phospholipids, other neutral lipids, and ceramide. These data strongly indicate that the prosaposin variant containing the exon 8-encoded three amino acids is dispensable for normal mouse development and fertility as well as for prosaposin secretion and its lysosomal function, at least in the presence of the prosaposin variant missing the exon 8-encoded three amino acids.

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Protection by prosaposin against ischemia-induced learning disability and neuronal loss

Cited by 16 publications

References 0 publications

Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Long-Term Inhibition of Renin-Angiotensin System Sustains Memory Function in Aged Dahl Rats

The Exon 8-Containing Prosaposin Gene Splice Variant Is Dispensable for Mouse Development, Lysosomal Function, and Secretion

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