Molecular Cloning and Characterization of a Novel Sequence, vof-16, with Enhanced Expression in Permanent Ischemic Rat Brain

Abstract

Studies are underway to clarify the molecular mechanisms of dementia. Especially in the case of Alzheimer's disease, 1) some kinds of related molecules have been isolated: amyloid precursor protein, 2) presenilin 1/2, 3,4) tau 5,6) and others. The disease-generating mechanisms involving these molecules are under vigorous investigation, and it has been found that some kinds of mutations and phosphorylations of these moleculues stimulate formation of neurofibrillary tangles, resulting in Alzheimer's disease. In the case of cerebrovascular dementia, causal mechanisms have also been studied, especially with respect to apoptosis. Although many molecules which are involved in apoptosis have been identified, 7) there is no evidence yet about which factors are specifically involved in vascular dementia. Furthermore, the moleculues involved in non-diathetic dementia with normal aging still remain to be identified.We previously demonstrated that chronic hypoperfusion induced by permanent occlusion of the bilateral common carotid arteries (2VO) in rats caused progressive and longlasting cognitive deficits, 8,9) dysfunction of new information learning in the early stage, and memory loss in the late stage, suggesting that those deficits are due to impairment of memory retention and/or the memory recall process. We also found progressive neuronal damage in the hippocampus and the white matter: neuronal cell loss in the CA1 subfield appeared 4 months but not 1 month after permanent 2VO, and rarefaction of the white matter was observed 1 month after permanent 2VO and markedly increased 4 months after the operation.10) White matter lesions are common findings in elderly persons and in patients with cognitive impairment. 11)These lesions also appear in vascular dementia 11) and Alzheimer's disease patients, 12) suggesting that this 2VO model is useful for investigating molecular mechanisms of the generation of dementia. We have also reported that a decrease of microtubule-associated protein 2 (MAP-2) and an increase of glial fibrillary acidic protein (GFAP) immunoreactivity are observed at an early stage of 2VO treatment. 13)Since it has been reported that MAP-2 is preferentially associated with dendritic processes as a marker for detection of early ischemic damage 14,15) and an increase of GFAP-positive cells accompanies reactive changes in astroglia after cerebral ischemia, 16) some kinds of molecular changes appear to occur in this 2VO model. In the present study, we tried to isolate genes related to this neuronal damage using the differential display reverse transcription-polymerase chain reaction (RT-PCR) method, and obtained more than 20 clones which had different expression levels in 2VO-and sham-operated rats. One of these clones, which we called vof-16, has a novel sequence of which the expression is markedly enhanced by 2VO treatment, and may be related to the cognitive impairment after chronic ischemia induced by 2VO. Here, the sequence of vof-16, and its distributions and characteristics are presented. We previously r...

Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood

“…For example, enhanced expression levels of ischemia-related factor vof-16 (probe set ID 1377778 at) is associated with neuronal damage and impairment of learning and memory performance (20); hippocampal ATRX (probe set ID 1385006 at) dysregulation is associated with numerous forms of X-linked mental retardation (21); overexpression of S100 calciumbinding protein A4 (probe set ID 1367846 at) is observed in several neurodegenerative disorders (22); and reduced dihydropyrimidinase-related protein 2 (probe set ID 1380728 at) is associated with age-related dementia. Therefore, the rat model of natural variations in maternal care could be potentially useful in the study of gene- environment-therapeutic interactions of genomic regions known to be involved in human disease.…”

Common prefrontal cortical gene expression profiles between adolescent SHR/NCrl and WKY/NCrl rats which showed inattention behavior

“…Vof-16, Thrsp). Vof-16, of which mRNA expression is enhanced in the permanent ischemic brain [51], has recently been associated with neuronal damage and impairment of learning and memory performance [51,52]. Thrsp, a gene previously implicated in lipid metabolism, has been shown to modulate the activity of thyroid hormone receptor ␤ (THRB) [53].…”

Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation

“…In IPC-treated glands, the expression of Vof16 was increased. The expression of Vof16 , encoding for the ischemia related factor Vof-16, has been described in the rat brain following chronic ischemia (63).…”

“…been described in the rat brain following chronic ischemia (63). Molecular arrays have become accessible research tools to assist in the study of the mechanisms underlying Pancreatic IPC was associated with a sharp reduction of Ncf1 expression.…”