Publications by authors named "Matias Röyttä"

38 Publications

Interaction between matrix metalloproteinase 3 and the epsilon4 allele of apolipoprotein E increases the risk of Alzheimer's disease in Finns.

Neurosci Lett 2004 Sep;367(3):336-9

Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Center for Laboratory Medicine, Tampere University Hospital, PO Box 2000, FIN-33521, Finland.

Polymorphisms affecting the expression of matrix metalloproteinases (MMPs), i.e. proteolytic enzymes that degrade intercellular material, have been found at position -1607 (1G/2G) in MMP1 and at -1171 (5A/6A) in MMP3. Interestingly, elevated levels of MMP1 and MMP3 have been observed in the brains of Alzheimer's disease (AD) patients and those of tissue inhibitors of MMPs in the cerebrospinal fluid of AD and Parkinson's disease (PD) patients, suggesting a role for MMPs in these disorders. The aim was to investigate a possible association between the afore-mentioned MMP1 and MMP3 polymorphisms and the risk of developing AD or PD. The polymorphisms were genotyped in 97 AD, 52 PD and 101 control patients. We found an interaction between MMP3*5A and APOE 4 alleles (P < 0.0001) which increases the risk of AD (OR: 23.7, 95% CI: 5.8-144.9, P < 0.0001) compared to those who possess neither MMP3*5A nor APOE 4. In conclusion, our finding suggests that the MMP3 gene, especially together with APOE 4, may contribute to the development of AD.
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http://dx.doi.org/10.1016/j.neulet.2004.06.027DOI Listing
September 2004

The perineurium modifies the effects of phenol and glycerol in rat sciatic nerve.

Acta Neuropathol 2004 Oct 5;108(4):319-31. Epub 2004 Aug 5.

Department of Pathology, Turku University Central Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland.

Endoneurial cell response and type of nerve fibre damage were studied after perineural injections of 7% phenol-aqua and pure glycerol. Our previous studies have shown that phenol and glycerol induce different types of nerve fibre degeneration after intraneural injections: phenol dissolves axons and Schwann cells inside the basal lamina tubes but glycerol breaks them down into cellular flakes. The current study investigated whether the difference in type of endoneurial damage also appears after perineural application and how the perineurium affects the effect of these neurolytic agents. Rat sciatic nerves were treated with perineural injections of 7% phenol-aqua or pure glycerol and were followed up to 6 months. The results support the previous findings that perineural phenol injection induces damage that covers almost the whole endoneurium, but glycerol injection results in minor subperineurial damage. An ultrastructural study showed that the endoneurial effects are much milder after perineural injection than after intraneural injections. Phenol-induced nerve fibre dissolving was only rarely seen and the nerve fibre damage appeared similar to that after regular Wallerian degeneration in both groups. Axonal regeneration began within 2 weeks of the injections. Endoneurial macrophages were numerous in the damaged area in many individual nerves even at 3-6 months in both groups, which may indicate impaired phagocytotic activity. Regenerating axonal sprouts were seen first at 1 week post injection and Schwann cells proliferated within 2 weeks in both groups. However, the number of axonal sprouts was higher (P=0.002) and the size of the sprouts appeared larger after glycerol injection at 4 weeks post injection. The present study shows that the effects of extraneurally applied neurolytic agents phenol and glycerol are modified by the perineurium. Phenol readily penetrates the perineurium, but glycerol causes only subperineurial damage. The type of damage is rather similar to regular Wallerian degeneration in both groups and the endoneurial effects differ from those seen after intraneural injections.
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http://dx.doi.org/10.1007/s00401-004-0896-1DOI Listing
October 2004

Herpesviruses in brains in Alzheimer's and Parkinson's diseases.

Ann Neurol 2003 Aug;54(2):267-71

Department of Virology, University of Turku, Turku, Finland.

We evaluated the association of HSV-1, HHV-6, and VZV with Alzheimer's disease (AD) and Parkinson's disease (PD). Brain specimens for viral DNA polymerase chain reaction represented 34 patients with AD, 40 with PD, and 40 controls. One AD patient (2.9%) was positive for HSV-1 DNA, 88.2% for HHV-6 DNA, and 26.5% for VZV DNA; 17.5% of PD patients were HSV-1 DNA-positive and 75% HHV-6-positive, whereas 40% had VZV DNA. Twenty-five percent of the controls were positive for HSV-1 DNA, 87.5% for HHV-6, and 27.5% for VZV. HSV-1, VZV, or HHV-6 DNA in brains was no additional risk factor for AD.
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http://dx.doi.org/10.1002/ana.10662DOI Listing
August 2003

The effect of combined neurolytic blocking agent 5% phenol-glycerol in rat sciatic nerve.

Acta Neuropathol 2003 Sep 10;106(3):261-70. Epub 2003 Jul 10.

Department of Anaesthesiology, Loimaa District Hospital, 32200 Loimaa, Finland.

Combined 5% phenol-glycerol has been used to treat cancer pain or spasticity and as sympathetic blocks. The major clinical problems have been the unpredictable effects on pain and on the duration of the blocks. Previously we have shown that intraneurally injected phenol induces haemorrhagic necrosis as well as dissolving of the nerve fibres. Glycerol, on the other hand, induces dispersion of nerve fibre debris into the endoneurium. We have now studied the effects of a combination of these two chemically different agents. The endoneurial and epineurial responses of rat peripheral nerve were followed after intraneural and perineural injections. Samples for electron microscopic and immunohistochemical studies were taken at 1-26 weeks after the injection. The intraneural phenol-glycerol injection resulted in gross endoneurial damage with partly or totally dissolved nerve fibres. Totally dissolved nerve fibres showed empty, collapsed basal lamina tubes and partly dissolved nerve fibres showed breaching of remaining degenerative debris into the endoneurial space. Axonal regeneration was delayed and was observed first after 2 weeks and it took 4 months before most of the nerve fibres were myelinated. The perineural injections resulted in partial subperineurial damage of the endoneurium morphologically similar to the results caused by the intraneural injection. An initial high accumulation of epineurial macrophages was noted at 1 and 2 weeks. An invasion of macrophages into the endoneurium occurred within 1 week after the intraneural and perineural injections and the number of endoneurial macrophages remained high for up to 6 months. The present study shows that glycerol added to phenol diminishes the necrotizing effect of phenol after an intraneural injection. Combined phenol-glycerol-induced nerve injury is reversible and the axons regenerate but residual morphological changes can be observed even after 6 months.
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http://dx.doi.org/10.1007/s00401-003-0730-1DOI Listing
September 2003

Absence of association between an intercellular adhesion molecule 1 gene E469K polymorphism and Alzheimer's disease in Finnish patients.

Neurosci Lett 2003 Jan;337(1):61-3

Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital, Finland.

Increased expression of intercellular adhesion molecule 1 (ICAM1), a protein known to contribute to inflammatory responses, has been detected in the brain tissue of patients with Alzheimer's disease (AD) and animals modelled to mimic AD or Parkinson's disease (PD). ICAM1 may, thus, be implicated in the pathogenesis of these disorders. Our purpose was to investigate whether genetic variants of the ICAM1 gene have a role in causing susceptibility to AD and/or PD. We genotyped the E469K polymorphism of ICAM1 in 196 AD, 52 PD and 202 control patients of Finnish origin. The distributions of the genotype and allele frequencies of the polymorphism did not differ significantly between the AD, PD or the control patients. We therefore conclude that the E469K polymorphism of ICAM1 is not a risk factor for AD or PD.
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http://dx.doi.org/10.1016/s0304-3940(02)01296-xDOI Listing
January 2003

Contralateral non-operated nerve to transected rat sciatic nerve shows increased expression of IL-1beta, TGF-beta1, TNF-alpha, and IL-10.

J Neuroimmunol 2002 Nov;132(1-2):11-7

Department of Pathology, University of Turku, Kiinanmyllynkatu 10, FIN-20520 Turku, Finland.

Recent reports indicate that after a peripheral nerve injury, the uninjured contralateral nerve is also affected. Because cytokines play an important role in the peripheral nerve injury, we studied the expression of five different mRNAs (interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-beta1) and interleukin-4 (IL-4)) in the contralateral, non-operated, left sciatic nerve when the right rat sciatic nerve was transected. This study extended up to 42 days after the transection. No IL-4 expression was noted. During the first 3 days, high expression of the other studied cytokines was noted in the endoneurium. At day 7, the expression diminished to the control levels. After this, a cyclic expression pattern appeared, which was most pronounced in the endoneurium at 35 days. We also show that the expression pattern in the endoneurium is different from that in the surrounding epi- and perineurium. Also, our present study shows clearly that contralateral nerves are poor controls after injury.
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http://dx.doi.org/10.1016/s0165-5728(02)00281-3DOI Listing
November 2002

The endoneurial response to microsurgically removed epi- and perineurium.

J Peripher Nerv Syst 2002 Sep;7(3):155-62

Department of Pathology, University of Turku, Kiinanmyllynkatu, Finland.

The purpose of the study was to examine the response of the endoneurium of the rat sciatic nerve after removal of the epi- and perineurium. For this purpose, segments (4-5 mm long) of the whole epi- and perineurium around the rat sciatic nerve were microsurgically removed (the peel-off area) and the endoneurium was left intact. The post-operative changes were followed up to 5 weeks post-operatively (PO) by histo- and immunohistochemical studies. Additionally, neuromorphometric analyses considering the number of Schwann cells, axons, macrophages and endothelial cells were examined in the peel-off area. The results showed that at the operative area the central part of the endoneurium (65% of the total area of the endoneurium) remained morphologically intact, but the outer part of the endoneurium (35% of the total area) reacted strongly and showed Wallerian type of degeneration. The number of axons and Schwann cells decreased 3 days PO. However, after 2 weeks the number of Schwann cells increased markedly and the highest number was noted 5 weeks PO. A great number of capillaries were observed in the outer part 1 week PO. A rapid invasion of macrophages was noted at the outer part of the endoneurium immediately after the operation. During the regeneration the endoneurial fibroblasts in the peripheral zone started to form minifascicle-like formations, which resulted in a distinct dense outer part of the endoneurium. This dense outer zone was preserved up to 5 weeks PO and participated in the formation of a new perineurium-like structure, but no distinct new perineurium was formed. At the border zone, areas beside the normal epi- and perineurium proliferation of preserved perineurial cells were noted, which fused to the outer part of the dense endoneurium. On focal areas, an attachment of the operated area to the adjoining muscle was observed. This study shows for the first time that despite the microsurgical removal of epi- and perineurium, the inner part of the endoneurium stays intact, but in the outer part of the endoneurium marked reactive changes ensue, probably to protect the injured peripheral nerve.
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http://dx.doi.org/10.1046/j.1529-8027.2002.02015.xDOI Listing
September 2002

Herpes simplex virus type 1 infection induces upregulation of interleukin-23 (p19) mRNA expression in trigeminal ganglia of BALB/c mice.

J Interferon Cytokine Res 2002 Jun;22(6):641-51

Department of Virology, the MediCity Research Laboratory, and the Turku Graduate School of Biomedical Sciences, University of Turku, FIN-20520 Turku, Finland.

We investigated the expression kinetics of several cytokines in trigeminal ganglia (TG) and in brains of BALB/c mice during the course of ocular herpes simplex virus type 1 (HSV-1) infection. All mice recovered from the infection within 2 weeks. The quantitative rapid real-time RT-PCR method was used to analyze interleukin-4 (IL-4), interferon-gamma (IFN-gamma), IL-12p35, IL-12p40, and the recently described IL-23 (p19) mRNA in TG, brain, and splenocyte samples. In TG, we found elevated expression of mRNA for IL-23 (p19) from early acute infection (day 3) to the beginning of the latent phase (day 14). The increase was not detected in brain or in the spleen. IL-4 expression occurred in both TG and brain from the beginning of the experiment to the latent phase. During the latent phase (days 14 and 31), IL-4 expression was significantly elevated in the brain when compared with the uninfected controls (p < 0.05). Considerable expression of IFN-gamma mRNA was detected in TG of mice during acute HSV-1 infection. The expression of IL-23 was detected also in the brains of the mice, even though no significant changes were found during the acute HSV-1 infection. This is, to our knowledge, the first report to show elevated expression of IL-23 (p19) mRNA (p < 0.05) during viral infection in TG of mice.
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http://dx.doi.org/10.1089/10799900260100123DOI Listing
June 2002