| 1 | Schizophr. Res. 2007 Nov 96: 257-66 |
|---|---|
| PMID | 17644312 |
| Title | The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients. |
| Abstract | schizophrenic brains exhibit various neuro-pathological changes in size, volume and structure as compared to normal brains. These structural abnormalities could be the result of apoptotic cell death. ARTS/SEPT4 protein plays an important role in induction and promotion of apoptosis. Though ARTS is highly expressed in the healthy human brain, most of tested schizophrenic brain samples showed no expression of ARTS protein. Specifically, using Western blot analysis with monoclonal anti-ARTS antibody we found that only 1 out of 14 schizophrenic samples (7%) showed a strong ARTS signal as compared to 10 out of 15 (66.6%) found in the normal controls group. Furthermore, using immunohistochemistry assay only 33.3% (5 of 15) (SE+/-12.5) of the schizophrenic patients samples showed any ARTS immunoreactivity as compared to (13 of 15) 87% (SE+/-9) of bipolar, (11 of 14) 78% (SE+/-11.3) of major depression and (10 of 14) 71% (SE+/-12.5) of normal controls. A four-fold reduction in apoptosis rate was measured in these schizophrenic samples as compared to average apoptosis rate found in all other samples. These data support the linkage between loss of ARTS expression and the loss of sensitivity towards apoptosis. Interestingly, levels of ARTS were significantly lower in male schizophrenic patients as compared to female schizophrenic patients, and males of all other control groups. We propose that ARTS may play an important role in the pathogenesis of schizophrenia and could be used as a marker for this disease. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Schizophr. Res. 2007 Nov 96: 257-66 |
| PMID | 17644312 |
| Title | The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients. |
| Abstract | schizophrenic brains exhibit various neuro-pathological changes in size, volume and structure as compared to normal brains. These structural abnormalities could be the result of apoptotic cell death. ARTS/SEPT4 protein plays an important role in induction and promotion of apoptosis. Though ARTS is highly expressed in the healthy human brain, most of tested schizophrenic brain samples showed no expression of ARTS protein. Specifically, using Western blot analysis with monoclonal anti-ARTS antibody we found that only 1 out of 14 schizophrenic samples (7%) showed a strong ARTS signal as compared to 10 out of 15 (66.6%) found in the normal controls group. Furthermore, using immunohistochemistry assay only 33.3% (5 of 15) (SE+/-12.5) of the schizophrenic patients samples showed any ARTS immunoreactivity as compared to (13 of 15) 87% (SE+/-9) of bipolar, (11 of 14) 78% (SE+/-11.3) of major depression and (10 of 14) 71% (SE+/-12.5) of normal controls. A four-fold reduction in apoptosis rate was measured in these schizophrenic samples as compared to average apoptosis rate found in all other samples. These data support the linkage between loss of ARTS expression and the loss of sensitivity towards apoptosis. Interestingly, levels of ARTS were significantly lower in male schizophrenic patients as compared to female schizophrenic patients, and males of all other control groups. We propose that ARTS may play an important role in the pathogenesis of schizophrenia and could be used as a marker for this disease. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Brain Nerve 2009 Apr 61: 419-28 |
| PMID | 19378812 |
| Title | [Functions of the septin cytoskeleton and its roles in dopaminergic neurotransmission]. |
| Abstract | Cytoskeletal polymers are component of cellular infrastructure that are required for fundamental biological processes ranging from cell division to brain functions. Unlike the knowledge available for tubulin and actin, our understanding of unconventional cytoskeletal structures composed of GTP-binding proteins belonging to the septin family is limited, despite their ubiquity and implications in human diseases. Recent studies have revealed that septin plays unique modulatory roles as an accessory component of microtubules and the actin cytoskeleton. Morphological analyses of the mammalian brain and neural cells have revealed that septins preferentially cluster beneath the extra-synaptic membrane domains in dendritic shafts and spine necks, presynaptic terminals of major neurons, and astroglial processes. Live imaging analysis revealed that septin polymers are remarkably stable in these clusters, which may serve as local cytoskeleton and/or scaffold for the organization of specialized cortical domains in neurons and glia. This hypothesis has been supported by the hypo-dopaminergic phenotype of mice that lack the SEPT4 subunit and the hyper-dopaminergic phenotype of those with excess SEPT4. In these cases, the septin scaffold in the dopamine neurons is considered as a determinant of the quantity of a subset of presynaptic molecules, including tSNAREs (membrane-fusion machinery) and the dopamine transporters. This finding in mouse models is in agreement with the recent findings that qualitative and/or quantitative dysregulation of septins is involved in neurodegenerative disorders such as Parkinson disease and psychological disorders such as schizophrenia and bipolar disorder. Studies on tubulin/actin indicate that a better understanding of the septin family of proteins will improve our insight into neuropathological phenomena in neurodegenerative and psychological disorders, which may help develop diagnostic markers and therapeutic strategies for such diseases. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Mol Brain 2013 -1 6: 35 |
| PMID | 23938054 |
| Title | Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice. |
| Abstract | In autosomal recessive early-onset Parkinsonism (PARK2), the pathogenetic process from the loss of function of a ubiquitin ligase parkin to the death of dopamine neurons remains unclear. A dominant hypothesis attributes the neurotoxicity to accumulated substrates that are exempt from parkin-mediated degradation. Parkin substrates include two septins; SEPT4/CDCrel-2 which coaggregates with ?-synuclein as Lewy bodies in Parkinson's disease, and its closest homolog SEPT5/CDCrel-1/PNUTL1 whose overload with viral vector can rapidly eliminate dopamine neurons in rats. However, chronic effects of pan-neural overload of septins have never been examined in mammals. To address this, we established a line of transgenic mice that express the largest gene product SEPT4(54kDa) via the prion promoter in the entire brain. Histological examination and biochemical quantification of SEPT4-associated proteins including ?-synuclein and the dopamine transporter in the nigrostriatal dopamine neurons found no significant difference between SEPT4(Tg/+) and wild-type littermates. Thus, the hypothetical pathogenicity by the chronic overload of SEPT4 alone, if any, is insufficient to trigger neurodegenerative process in the mouse brain. Intriguingly, however, a systematic battery of behavioral tests revealed unexpected abnormalities in SEPT4(Tg/+) mice that include consistent attenuation of voluntary activities in distinct behavioral paradigms and altered social behaviors. Together, these data indicate that septin dysregulations commonly found in postmortem human brains with Parkinson's disease, schizophrenia and bipolar disorders may be responsible for a subset of behavioral abnormalities in the patients. |
| SCZ Keywords | schizophrenia, schizophrenic |