Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy

Table 1 Summary of polyamine-related findings in human schizophrenia studies

No significant differences in the distribution of the genotypes of the SAT-1415 T/C SNP between schizophrenia patients and healthy controls[54].

CFG study identified AZIN 1 as a candidate gene for schizophrenia[55].

DNA microarray and in situ hybridization studies show decreased AZIN 1 expression in schizophrenia. No influence of neuroleptic treatment[56].

OAT expression is reduced in samples of schizophrenia individuals[56,57].

No differently expressed genes implicated in PA metabolism in two large schizophrenia cohorts[58].

PAO activity is lower in blood plasma of acute and chronic schizophrenia patients[59-62].

PAO activity increased in blood sera of schizophrenic patients[64,65], reduction by electroconvulsive therapy[62].

ODC activity and cellular expression is normal in brain autopsy samples from people who suffered from schizophrenia[65,66].

SMOX activity is markedly higher in sera of schizophrenic patients[67].

AMDI and SAT1 activities are unaltered in brain tissue of schizophrenia individuals[65].

Density of AGMAT-containing interneurons is reduced in the hippocampus of schizophrenia patients[43].

Increased ARG activity in the CSF of schizophrenia patients[67].

Increased ARGII activity and protein expression in postmortem brain tissue in schizophrenia[68].

ARG activity is lower in plasma of schizophrenia individuals[71].

Elevated blood concentrations of spermine and/or spermidine in drug-naïve and treated schizophrenia patients[73-75].

Long-term neuroleptic treatment reduces spermine levels[76,77].

Increased concentrations of spermidine and total PA in fibroblasts from schizophrenia patients (reviewed in[11]).

PA levels normal in postmortem brain tissue of schizophrenia persons[65].

Elevated levels of spermine, spermidine and putrescine in brains of psychotic individuals[77].

Increased agmatine concentrations in blood plasma and postmortem brains of individuals with first episode and chronic schizophrenia[68,78-80].

Antipsychotic treatment decreases blood agmatine levels[77].

Reduced blood agmatine concentrations in early-onset schizophrenia[81].

Increased concentrations of SAM in brain samples of schizophrenia patients[82].

SNP: Singlenucleotide polymorphism; OAT: Ornithine aminotransferase; ODC: Ornithine decarboxylase; SMOX: Spermine oxidase; AGMAT: Agmatinase; AMD: S-adenosylmethionine decarboxylase; ARG: Arginase; PA: Polyamines; CSF: Cerebrospinal fluid; CFG: Convergent functional genomics; SAM: S-adenosylmethionine; SAT1: Spermidine/Spermine N1 acetyltransferase; PAO: Polyamine oxidase; AZIN: Antizyme inhibitor.

Table 2 Summary of polyamine-related findings in studies of animal models

Neuronal expression of ODC increased in rats with neonatal lesion of the ventral hippocampus[85].

Neuronal expression of SMOX increased in rats with neonatal lesion of the ventral hippocampus (unpublished).

Increased brain levels of putrescine, spermidine, spermine and arginine but decreased levels of agmatine were measured in rat offspring after maternal immune activation[86].

Agmatine disrupts prepulse inhibition in rats[87].

Agmatine attenuates the disruptive effects of phencyclidine on prepulse inhibition[88,89].

Injection of phencyclidine alters arginine metabolism in rat brain[90].

Withdrawal from repeated phencyclidine administration alters ARG activity and the levels of arginine metabolites in rat brain tissue[91,92].

No schizophrenia-like behavior in transgenic animals that overexpress ODC and/or SAT1[91].

SMOX overexpression in mice leads to glutamate excitotoxicity[91,92], a characteristic feature of “human” schizophrenia.

ARG: Arginase; ODC: Ornithine decarboxylase; SAT1: Spermidine/SpermineN1 acetyltransferase; SMOX: Spermine oxidase.