Johanna O Ojala - Academia.edu (original) (raw)

Papers by Johanna O Ojala

Acta Physiologica Scandinavica, Apr 1, 1989

Han-Wistar rats were exposed to a 194-200 h swimming protocol which caused a significant increase... more Han-Wistar rats were exposed to a 194-200 h swimming protocol which caused a significant increase in the cardiac weight. The levels of various tissue antioxidants were assayed from the myocardium of the right ventricle and from the left ventricle (subendo- and subepimyocardium). This endurance training decreased the activities of catalase in the right ventricle and in the subendo- and subepimyocardium and Cu,Zn-superoxide dismutase in the subendomyocardium as well as the concentration of vitamin E in the right ventricle and in the subendomyocardium. Also, the activity of thioredoxin reductase decreased in each part of myocardium and that of glutathione reductase in the right ventricle and in the subepimyocardium. The activity of glucose-6-phosphate dehydrogenase increased in the right ventricle and in the subepimyocardium. The activity of glutathione peroxidase and the total tissue contents of carnosine and anserine and tissue sulphydryl groups remained unchanged as compared to the control group. The endurance training caused only minor changes in the regional distribution of antioxidants. The major findings were the disappearance of the difference in the activity of catalase between the right and the left ventricle and the increase in the activity of glucose-6-phosphate dehydrogenase as compared to that of the left ventricle. The results show that endurance training by swimming decreases the level of cardiac antioxidants. This decrease may be due to the increased oxygen metabolism and the subsequent increase in the formation of oxygen free radicals, which could deplete the antioxidant pool.

Alzheimers & Dementia, Jul 1, 2006

The genetic component has shown to be one of the most important etiological factors in Alzheimer'... more The genetic component has shown to be one of the most important etiological factors in Alzheimer's disease (AD) due to a great number of cases presenting familial recurrence. Some studies show that the immunological system must play a role in the neurodegenerative process of Alzheimer's disease. The mutation of a single nucleotide on the 5' region of the interleukin-6 gene promoter (C or G on the base-174) has been identified. Individuals with the G allele on the position-174 have shown increased levels of interleukin 6 when compared to those with C/C genotype. Therefore, some studies correlate the presence of G allele to the risk factor for AD development, despite controversies on the literature. Objective: This study aims at investigating the inflammatory cytokine polymorphism distribution, interleukin 6 in an AD group and in two control groups. Whole blood DNA samples were obtained from 215 individuals, 78 Alzheimer's disease (AD) patients; 60 elderly controls (EC) and 77 young controls (YC). Methods: The polymorphism genotyping of interleukin 6 consisted of PCR-RFLP technique, where specific oligonucleotides and the PCR product was digested with NlaIII restriction enzyme. This material was submitted to GTG 4% agarose gel electrophoresis and stained with Ethidium Bromide for visualizing the mutation. Results: Our results showed that the genotype distribution of interleukin 6 gene in the samples was balanced with Hardy-Weinberg. Conclusions: Therefore, these results show no association of the genotype with Alzheimer's disease. Finally, it is necessary to elucidate risk factors, a better comprehension of the AD neuroimmune mechanisms.

Neurobiology of Aging, 2011

We have established a novel transgenic rat line carrying human microtubule-associated protein Tau... more We have established a novel transgenic rat line carrying human microtubule-associated protein Tau-40 with mutation P301L. hTau-40/P301L transgenic male and female rats were followed up to 2 years of age. The hTau-40/P301L rats expressed human tau mRNA and protein in the limbic cortex and associated white matter, hippocampus and spinal cord. With increasing age, the staining density for phosphorylated tau increased in all these areas. Neither silver stains nor Fluoro-Jade staining indicated the presence of dying neurons, or axonal degeneration, and there was no evidence of increased gliosis or inflammation. However, some neurons did display dendritic abnormalities, and immunoblots revealed the presence of sarcosyl insoluble tau. A large test battery revealed no behavioral abnormalities in these rats, except a mild hyperactivity in the elevated plus maze. In conclusion, this transgenic tau rat may be a useful model for 'pretangle' pathology, although in this study conditions were not sufficient to induce significant neuronal loss or behavioral deficits.

Reactive Oxygen Species

In stroke, increased oxidative stress (OS), mediated by reactive oxygen species (ROS) including H... more In stroke, increased oxidative stress (OS), mediated by reactive oxygen species (ROS) including H2O2 release, can induce changes that lead to neural production of amyloid-β (Aβ), a hallmark protein in the brains of Alzheimer's disease (AD) patients. Aβ peptide can also induce OS by itself or by activating microglia to release ROS. Estrogenic compounds can protect neurons against Aβ-and OS-induced cell death. Aβ-and OS-induced cell death is another hallmark of AD. We have studied OS-related cell damage by exposing rat primary hippocampal neurons and differentiated human SH-SY5Y neuroblastoma cells to H2O2 or Aβ1-42 and evaluated the neuroprotective potential of 17β-estradiol (E2), estrone (E1), tamoxifen (Tam), 4-OH-tamoxifen (4-OH-Tam), diethylstilbestrol (Des) and genistein (Gen) against OS. These compounds have differences in estrogen receptor (ER) binding affinities and their number of antioxidative-OH groups varies. The cell damage indicator was the lactate dehydrogenase release into culture medium. Treatment with 5 nM E2, Gen, or 4-OH-Tam for 24 h before and after the H2O2 insult was neuroprotective in both hippocampal and SH-SY5Y cultures. E2 and Gen were neuroprotective against Aβ1-42-mediated toxicity. Protection by E2 was partially mediated by Bcl-2, Bcl-xL, and BAG-1. Tam also increased Bcl-2 and Bcl-xL but was much less neuroprotective. Gen increased amyloid precursor protein (APP) synthesis, but γ-secretase component PS-1 was reduced, suggesting that Gen can increase the production of neurotrophic soluble APP. Des increased Aβ production. In conclusion, Gen shows comparable neuroprotective efficacy to E2, and seems also to reduce Aβ production in our study. However, other neuroprotective mechanisms may exist, and further studies on this subject will enhance our understanding in this respect.

Journal of clinical medicine, Jan 21, 2017

The role of interleukins (ILs) and oxidative stress (OS) in precipitating neurodegenerative disea... more The role of interleukins (ILs) and oxidative stress (OS) in precipitating neurodegenerative diseases including sporadic Alzheimer's disease (AD), requires further clarification. In addition to neuropathological hallmarks-extracellular neuritic amyloid-β (Aβ) plaques, neurofibrillary tangles (NFT) containing hyperphosphorylated tau and neuronal loss-chronic inflammation, as well as oxidative and excitotoxic damage, are present in the AD brain. The pathological sequelae and the interaction of these events during the course of AD need further investigation. The brain is particularly sensitive to OS, due to the richness of its peroxidation-sensitive fatty acids, coupled with its high oxygen demand. At the same time, the brain lack robust antioxidant systems. Among the multiple mechanisms and triggers by which OS can accumulate, inflammatory cytokines can sustain oxidative and nitrosative stress, leading eventually to cellular damage. Understanding the consequences of inflammation an...

Journal of Neuroinflammation, 2012

Background Alzheimer’s disease (AD) involves increased accumulation of amyloid-β (Aβ) plaques and... more Background Alzheimer’s disease (AD) involves increased accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles as well as neuronal loss in various regions of the neocortex. Neuroinflammation is also present, but its role in AD is not fully understood. We previously showed increased levels of pro-inflammatory cytokine interleukin-18 (IL-18) in different regions of AD brains, where it co-localized with Aβ-plaques, as well as the ability of IL-18 to increase expression of glycogen synthase kinase-3β (GSK-3β) and cyclin dependent kinase 5, involved in hyperphosphorylation of tau-protein. Elevated IL-18 has been detected in several risk conditions for AD, including obesity, type-II diabetes, and cardiovascular diseases as well as in stress. Methods We differentiated SH-SY5Y neuroblastoma cells as neuron-like and exposed them to IL-18 for various times. We examined the protein levels of amyloid-β precursor protein (APP) and its processing products, its cleaving enzymes, involve...

Current Pharmaceutical Design

Background: A diverse array of data has been associated with autism spectrum disorder (ASD), refl... more Background: A diverse array of data has been associated with autism spectrum disorder (ASD), reflecting the complexity of its pathophysiology as well as its heterogeneity. Two important hubs have emerged, the placenta/prenatal period and the postnatal gut, with alterations in mitochondria functioning crucial in both. Methods: Factors acting to regulate mitochondria functioning in ASD across development are reviewed in this article. Results: Decreased vitamin A, and its retinoic acid metabolites, lead to a decrease in CD38 and associated changes that underpin a wide array of data on the biological underpinnings of ASD, including decreased oxytocin, with relevance both prenatally and in the gut. Decreased sirtuins, poly-ADP ribose polymerase-driven decreases in nicotinamide adenine dinucleotide (NAD+), hyperserotonemia, decreased monoamine oxidase, alterations in 14-3-3 proteins, microRNA alterations, dysregulated aryl hydrocarbon receptor activity, suboptimal mitochondria functioning...

Journal of Neuroimmunology, 2010

Immunology Letters, Jun 15, 2007

Journal of Neuroimmunology, 2012

Background: Emergent seizures are common in Alzheimer’s disease (AD) in both humans and animal mo... more Background: Emergent seizures are common in Alzheimer’s disease (AD) in both humans and animal models [1,2], although the mechanisms mediating this are unknown. It seems that about 1.5% to 10% of AD patients experience seizure activity, with the highest prevalence in early onset AD [3]. This raises the question as to whether there is a subtype of AD that is seizure associated and may be linked to differential changes and possibly to differential treatment. Induction of kynurenine pathway member indoleamine 2,3-dioxygenase (IDO) in the brain can lead subsequent quinolinic acid (QA) production (Fig. 1). QA mediates neuronal excitotoxicity via the N-methyl-D-aspartate receptor (NMDAr) [6] and thus is a possible mediator of both seizures and neuronal loss [4,5]. IDO is induced at least by interferon-γ (IFNγ), but other inflammatory factors may also contribute to its increase [7,8]. One such factor is Interleukin-18 (IL-18; former IFNγ inducing factor IGIF, IL-1γ). IL-18 is induced by st...

International journal of tryptophan research : IJTR, 2010

Emergent seizures are common in Alzheimer's disease (AD), although the mechanisms mediating t... more Emergent seizures are common in Alzheimer's disease (AD), although the mechanisms mediating this are unknown. It is proposed that stress induced interleukin-18 (IL-18), via interferon-gamma (IFNy) and independently, increases indoleamine 2,3-dioxygenase (IDO) and subsequent quinolinic acid (QA) in microglia. QA increases seizures and concurrently contributes to neuronal loss via excitotoxicity. The ApoE4 allele interacts with IL-18 polymorphisms to increase the risk of AD, and seems likely to potentiate the emergence of seizures. Concurrent changes in IDO and the kynurenine pathways at the blood-brain-barrier (BBB) have implications for treatment, including in the efficacy of different anti-hypertensives. Melatonin is proposed to inhibit these overlapping excitotoxic and neurodegenerative processes, and would be a useful adjunctive treatment.

Progress in neurobiology, 2011

Alzheimer's disease is a tauopathy which involves the deposition of microtubule-associated ta... more Alzheimer's disease is a tauopathy which involves the deposition of microtubule-associated tau proteins into neurofibrillary tangles. Post-translational modifications, in particular site-specific phosphorylations, affect the conformation of tau protein which is an intrinsically disordered protein. These structural changes significantly increase the affinity of tau protein for certain molecular chaperones. Hsp90 is a major cellular chaperone which assembles large complexes with a variety of co-chaperones. The main function of Hsp90 complexes is to maintain protein quality control and assist in protein degradation via proteasomal and autophagic-lysosomal pathways. Tau protein is a client protein for these Hsp90 complexes. If the tau protein is in an abnormal or modified form, then it can trigger the recruitment of CHIP protein, a co-chaperone with E3 activity, to the complex which induces the ubiquitination of tau protein and activates its downstream degradation processes. Large i...

Frontiers in cellular neuroscience, 2014

Chronic inflammation and oxidative stress (OS) are present in Alzheimer's disease (AD) brains... more Chronic inflammation and oxidative stress (OS) are present in Alzheimer's disease (AD) brains in addition to neuronal loss, Amyloid-β (Aβ) plaques and hyperphosphorylated tau-protein neurofibrillary tangles (NFTs). Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18), are elevated in post-mortem AD brains. IL-18 can modulate the tau kinases, Cdk5 and GSK3β, as well as Aβ-production. IL-18 levels are also increased in AD risk diseases, including type-2 diabetes and obesity. Here, we explored other IL-18 regulated proteins in neuron-like SH-SY5Y cells. Differentiated SH-SY5Y cells, incubated with IL-18 for 24, 48, or 72 h, were analyzed by two-dimensional gel electrophoresis (2D-DIGE). Specific altered protein spots were chosen and identified with mass spectrometry (MS) and verified by western immunoblotting (WIB). IL-18 had time-dependent effects on the SH-SY5Y proteome, modulating numerous protein levels/modifications. We concentrated on thos...

Progress in Neurobiology, 2013