Regulation of SSAT expression by synaptic activity

Ingi, Tatsuya; Worley, Paul F.; Lanahan, Anthony A.

doi:10.1046/j.0953-816x.2001.01529.x

Cited by 20 publications

(14 citation statements)

References 26 publications

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“…The gene product implicated in SRS may be directly or indirectly involved in synaptic plasticity-based learning mechanisms [24, 25]. Thus, alteration of signaling pathway function as a result of genetic mutations in the SMS gene may disrupt the mechanisms necessary for the development and maintenance of new synapses.…”

Section: Discussionmentioning

confidence: 99%

The impact of spermine synthase (SMS) mutations on brain morphology

et al. 2009

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Snyder-Robinson syndrome (SRS) is a form of X-linked mental retardation resulting from mutations in spermine synthase (SMS), which impact neurodevelopment and cognitive outcome. We obtained cerebral, cerebellum, hippocampus, and red nucleus volumes from two males with SRS and 24 age-and gender-matched typically developing controls using volumetric neuroimaging analyses. Total brain volume was enlarged in males with SRS while cerebellum, hippocampus, and red nucleus volumes tended to be reduced compared to controls. Mutations of the X chromosome may modulate the risk for mental retardation through altered early neurodevelopment, disruption in receptor function, and ongoing neural organization and plasticity. Disruption of SMS function may negatively affect regional brain volumes that subserve cognitive and motor abilities. This research provides valuable insight into the effects of polyamine function on brain development.

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Section: Discussionmentioning

confidence: 99%

The impact of spermine synthase (SMS) mutations on brain morphology

et al. 2009

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“…SSAT-induced alterations in polyamine content could therefore alter brain function. 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: 97%

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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“…Despite the fact that L-LTP inducing stimuli or learning turns on (or off) the expression of a set of common genes in the hippocampal neurons involved, the specific genes that mediate specific aspects of LTM have not been fully established (Ingi, Worley, and Lanahan, 2001;Matsuo, Murayama, Saitoh, Sakaki, and Inokuchi, 2000;Qian, Gilbert, Colicos, Kandel, and Kuhl, 1993). Nevertheless, evidence seems quite strong that BDNF is critically involved in LTM.…”

Section: Formation (Acquisition or Encoding) Of Ltmmentioning

confidence: 99%

BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory?

Lü

Christian

2008

Neurobiology of Learning and Memory

672

464

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It is generally believed that late-phase long-term potentiation (L-LTP) and long-term memory (LTM) require new protein synthesis. Although the full complement of proteins mediating the long-lasting changes in synaptic efficacy have yet to be identified, several lines of evidence point to a crucial role for activity-induced brain derived neurotrophic factor (BDNF) expression in generating sustained structural and functional changes at hippocampal synapses thought to underlie some forms of LTM. In particular, BDNF is sufficient to induce the transformation of early to late phase LTP in the presence of protein synthesis inhibitors, and inhibition of BDNF signaling impairs LTM. Despite solid evidence for a critical role of BDNF in L-LTP and LTM, many issues are not resolved. Given that BDNF needs to be processed in Golgi outposts localized at the branch point of one or few dendrites, a conceptually challenging problem is how locally synthesized BDNF in dendrites could ensure synapse-specific modulation of L-LTP. An interesting alternative is that BDNF-TrkB signaling is involved in synaptic tagging, a prominent hypothesis that explains how soma-derived protein could selectively modulate the tetanized (tagged) synapse. Finally, specific roles of BDNF in the acquisition, retention or extinction of LTM remain to be established.

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Regulation of SSAT expression by synaptic activity

Cited by 20 publications

References 26 publications

The impact of spermine synthase (SMS) mutations on brain morphology

The impact of spermine synthase (SMS) mutations on brain morphology

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

BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory?

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Regulation of SSAT expression by synaptic activity

Cited by 20 publications

References 26 publications

The impact of spermine synthase (SMS) mutations on brain morphology

The impact of spermine synthase (SMS) mutations on brain morphology

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

BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory?

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