Spermidine/spermine N1-acetyltransferase overexpression in mice induces hypoactivity and spatial learning impairment

Kaasinen, Selma K.; Oksman, Mari; Alhonen, Leena; Tanila, Heikki; Jänne, Juhani

doi:10.1016/j.pbb.2004.02.001

Cited by 31 publications

(22 citation statements)

References 53 publications

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“…In addition, the intracerebroventricular administration of spermidine antagonizes the deficits in working memory induced by 7-chlorokynurenic acid, a NMDA receptor antagonist, in the radial maze (Nishiga and Kamei 2003) and attenuates the memory impairment induced by olfactory bulbectomy in the passive avoidance task (Tadano et al 2004). Interestingly, female transgenic mice overexpressing the polyamine catabolic enzyme, spermidine/spermine N-1-acetyltransferase, perform worse than syngenic females in a radial maze task (Kaasinen et al 2004). Previous studies have shown that the NMDA receptor is involved in the acquisition of inhibitory avoidance (Roesler et al 2003) and fear conditioning, but the role of NMDA in its consolidation is not established.…”

Section: Discussionmentioning

confidence: 99%

Systemic administration of polyaminergic agents modulate fear conditioning in rats

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Systemic administration of polyaminergic agents modulate fear conditioning in rats

et al. 2007

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“…Kainate-induced seizures increase SSAT activity (72), and transgenic overexpression of SSAT protects from kainate (77) and epilepsy-like seizure activity induction by pentylenetetrazol (77). These SSAT transgenic mice also showed a reduced activity and spatial learning impairment (78).…”

Section: Physiological or Pathophysiological Effects Of Altered Ssat mentioning

confidence: 99%

Spermidine/spermine-N¹-acetyltransferase: a key metabolic regulator

Pegg¹

2008

American Journal of Physiology-Endocrinology and Metabolism

298

305

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Spermidine/spermine-N(1)-acetyltransferase (SSAT) regulates cellular polyamine content. Its acetylated products are either excreted from the cell or oxidized by acetylpolyamine oxidase. Since polyamines play critical roles in normal and neoplastic growth and in ion channel regulation, SSAT is a key enzyme in these processes. SSAT is very highly regulated. Its content is adjusted in response to alterations in polyamine content to maintain polyamine homeostasis. Certain polyamine analogs can mimic the induction of SSAT and cause a loss of normal polyamines. This may have utility in cancer chemotherapy. SSAT activity is also induced via a variety of other stimuli, including toxins, hormones, cytokines, nonsteroidal anti-inflammatory agents, natural products, and stress pathways, and by ischemia-reperfusion injury. These increases are initiated by alterations in Sat1 gene transcription reinforced by alterations at the other regulatory steps, including protein turnover, mRNA processing, and translation. Transgenic manipulation of SSAT activity has revealed that SSAT activity links polyamine metabolism to lipid and carbohydrate metabolism by means of alterations in the content of acetyl-CoA and ATP. A high level of SSAT stimulates flux through the polyamine biosynthetic pathway, since biosynthetic enzymes are induced in response to the fall in polyamines. This sets up a futile cycle in which ATP is used to generate S-adenosylmethionine for polyamine biosynthesis and acetyl-CoA is consumed in the acetylation reaction. A variety of other effects of increased SSAT activity include death of pancreatic cells, blockage of regenerative tissue growth, behavioral changes, keratosis follicularis spinulosa decalvans, and hair loss. These are very likely due to changes in polyamine and putrescine levels, although increased oxidative stress via the oxidation of acetylated polyamines may also contribute. Recently, it was found that the SSAT protein and/or a related protein, thialysine acetyltransferase, interacts with a number of other important proteins, including the hypoxia-inducible factor-1 alpha-subunit, the p65 subunit of NF-kappaB, and alpha9beta1-integrin, altering the function of these proteins. It is not yet clear whether this functional alteration involves protein acetylation, local polyamine concentration changes, or other effects. It has been suggested that SSAT may also be a useful target in diseases other than cancer, but the wide-ranging physiological and pathophysiological effects of altered SSAT expression will require very careful limitation of such strategies to the relevant cells to avoid toxic effects.

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“…Brain tumors in general are an uncommon cause of acute brain hemorrhage. It is estimated that hemorrhage occurs in approximately 0.8 to 10.2% of brain tumors and is the presenting sign in an even fewer number of cases [13]. Intracranial tumors that have a recognized tendency to bleed include metastatic neoplasms; most commonly clear cell renal cell carcinoma, melanoma, choriocarcinoma, and bronchogenic carcinoma [14].…”

Section: Discussionmentioning

confidence: 99%

Anaplastic Astroblastoma Presenting as Massive, Sudden-Onset, Intraparenchymal Hemorrhage

Johnson¹,

Bonnin²,

Boaz

et al. 2010

Pediatr Neurosurg

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Astroblastoma is a rare primary glial tumor of children and young adults, typically located in the cerebral hemispheres and presenting as a well-circumscribed, nodular, often cystic enhancing mass. The existence of astroblastoma as a distinct clinicopathologic entity has long been debated but is recognized in the 2007 WHO classification of CNS tumors. The grading of these tumors remains unsettled. Currently, no grade has been established and there are no clearly defined diagnostic criteria for low- or high-grade tumors. Astroblastomas in general are thought to have a favorable outcome with low rates of recurrence following gross total resection. We report a case of astroblastoma with ‘high-grade/anaplastic’ histology in a 12-year-old, previously healthy girl. The patient experienced severe, sudden-onset headache, and quickly became comatose. Head CT showed a massive intraparenchymal hemorrhage in the right frontal lobe with surrounding edema. She underwent emergent posterior frontal craniotomy for decompression and hematoma evacuation. Pathologic examination revealed a sharply demarcated hemorrhagic heterogeneous glial tumor with focal papillary architecture, densely hyalinized blood vessels, and intensely GFAP-positive perivascular cells. The tumor showed unequivocal high-grade features including an elevated proliferative index. The diagnosis of anaplastic astroblastoma was rendered. The patient expired on postoperative day 30. This case illustrates the potential poor outcome of high-grade astroblastoma and highlights the morphologic heterogeneity of this rare neoplasm.

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Spermidine/spermine N1-acetyltransferase overexpression in mice induces hypoactivity and spatial learning impairment

Cited by 31 publications

References 53 publications

Systemic administration of polyaminergic agents modulate fear conditioning in rats

Systemic administration of polyaminergic agents modulate fear conditioning in rats

Spermidine/spermine-N¹-acetyltransferase: a key metabolic regulator

Anaplastic Astroblastoma Presenting as Massive, Sudden-Onset, Intraparenchymal Hemorrhage

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Spermidine/spermine N1-acetyltransferase overexpression in mice induces hypoactivity and spatial learning impairment

Cited by 31 publications

References 53 publications

Systemic administration of polyaminergic agents modulate fear conditioning in rats

Systemic administration of polyaminergic agents modulate fear conditioning in rats

Spermidine/spermine-N1-acetyltransferase: a key metabolic regulator

Anaplastic Astroblastoma Presenting as Massive, Sudden-Onset, Intraparenchymal Hemorrhage

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Spermidine/spermine-N¹-acetyltransferase: a key metabolic regulator