Jyrki Rintala - Academia.edu (original) (raw)

Papers by Jyrki Rintala

Molecular Psychiatry, 2002

type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part... more type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA 2 and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.

NeuroReport, 1999

The mechanism by which chronic lithium exerts its therapeutic effect in brains of bipolar patient... more The mechanism by which chronic lithium exerts its therapeutic effect in brains of bipolar patients is not known. One possibility, suggested by our demonstration in the rat brain, is that chronic lithium inhibits turnover of arachidonic acid (AA) by reducing the activity of an AA-specific phospholipase A2 (PLA2). To test this further, mRNA levels of two AA-specific PLA2s, cytosolic PLA2 (cPLA2) type IV and intracellular PLA2 (iPLA2) type VIII, and protein level of cPLA2 were quantified in the brain of rats given lithium for 6 weeks. Chronic lithium markedly reduced brain mRNA and protein level of cPLA2, but had no effect on mRNA level of iPLA2. These results suggest that the final common path effect of chronic lithium administration is to reduce turnover of AA in brain by down-regulating cPLA2.

Molecular Psychiatry, 2002

type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part... more type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA 2 and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.

Journal of Neurochemistry, 2001

Both (Li 1 ) and valproic acid (VPA) are effective in treating bipolar disorder, but the pathway ... more Both (Li 1 ) and valproic acid (VPA) are effective in treating bipolar disorder, but the pathway by which either works, and whether it is common to both drugs, is not agreed upon. We recently reported, using an in vivo fatty acid model, that Li 1 reduces the turnover rate of the second messenger arachidonic acid (AA) by 80% in brain phospholipids of the awake rat, without changing turnover rates of docosahexaenoic or palmitic acid. Reduced AA turnover was accompanied by down-regulation of gene expression and protein levels of an AA-speci®c cytosolic phospholipase A 2 (cPLA 2 ). To see if VPA had the same effect on AA turnover, we used our in vivo fatty acid model in rats chronically administered VPA (200 mg/ kg, i.p. for 30 days). Like Li 1 , VPA treatment signi®cantly decreased AA turnover within brain phospholipids (by 28± 33%), although it had no effect on cPLA 2 protein levels. Thus, both mood stabilizers, Li 1 and VPA have a common action in reducing AA turnover in brain phospholipids, albeit by different mechanisms.

Alcoholism: Clinical and Experimental Research, 1997

Aging and chronic alcohol consumption can cause degenerative changes in the cerebellar cortex. In... more Aging and chronic alcohol consumption can cause degenerative changes in the cerebellar cortex. In this study, the effects of aging and lifelong alcohol consumption on cerebellar cortical layer volumes (molecular and granular) and also white matter layer volumes were studied in alcohol-preferring (AA) and nonpreferring (ANA) rats of both sexes. The ethanol-consuming animals (EtOH) had 12% (wlv) ethanol as the only available fluid from 4 to 22 months of age, whereas the young (3 month) and old controls (24 months) had only water to drink. The volumes of molecular, granular, and white matter layers of the cerebellar vermis in folia II, IV, VII, and X were measured by using systematic sampling and a point-counting method. The volumes of the granular and white matter layers showed consistent increase between 3 and 24 months of age, whereas the volume of the molecular layer remained unchanged with increasing age. Individual ethanol intake was measured over a 1-week period at the beginning and at the end of chronic ethanol exposure. Significant (ANOVA, p = 0.0oO) sex difference was found in the drinking behavior in both lines, with females consuming more alcohol than males (daily ethanol consumption at 22 months of age 3.2 f 0.3 vs. 7.1 f 0.3 glkg for AA males and females; 3.2 f 0.3 vs. 5.4 f 0.4 glkg for ANA males and females, respectively). The only ethanol-induced effect on the cerebellum was observed in ANA-EtOH females with a 15% reduction in the volumes of the molecular and granular layer in folium II compared with agematched controls and a significant ( p c 0.05, analysis of covariance with ethanol intake as a covariate) line difference in folium II (molecular and granular layers) was observed between ANA-EtOH females and AA-EtOH females. Furthermore, the volume of the molecular layer in folium II was significantly ( p c 0.05, analysis of covariance with ethanol intake and body weights as covariates) reduced for ANA-EtOH females, compared with ANA-EtOH males indicating a sex difference in the cerebellar degeneration due to chronic alcohol consumption. Of the three layers studied, the white matter layer was the most resistant layer to the effects caused by chronic alcohol consumption. In view of the fact that AA and ANA rats of both sexes differ regarding the drinking behavior and ethanol metabolism, they provide an important model for further research on ethanol-induced pathological changes in the central nervous system.

Molecular Psychiatry, 2002

type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part... more type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA 2 and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.

NeuroReport, 1999

The mechanism by which chronic lithium exerts its therapeutic effect in brains of bipolar patient... more The mechanism by which chronic lithium exerts its therapeutic effect in brains of bipolar patients is not known. One possibility, suggested by our demonstration in the rat brain, is that chronic lithium inhibits turnover of arachidonic acid (AA) by reducing the activity of an AA-specific phospholipase A2 (PLA2). To test this further, mRNA levels of two AA-specific PLA2s, cytosolic PLA2 (cPLA2) type IV and intracellular PLA2 (iPLA2) type VIII, and protein level of cPLA2 were quantified in the brain of rats given lithium for 6 weeks. Chronic lithium markedly reduced brain mRNA and protein level of cPLA2, but had no effect on mRNA level of iPLA2. These results suggest that the final common path effect of chronic lithium administration is to reduce turnover of AA in brain by down-regulating cPLA2.

Molecular Psychiatry, 2002

type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part... more type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA 2 and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.

Journal of Neurochemistry, 2001

Both (Li 1 ) and valproic acid (VPA) are effective in treating bipolar disorder, but the pathway ... more Both (Li 1 ) and valproic acid (VPA) are effective in treating bipolar disorder, but the pathway by which either works, and whether it is common to both drugs, is not agreed upon. We recently reported, using an in vivo fatty acid model, that Li 1 reduces the turnover rate of the second messenger arachidonic acid (AA) by 80% in brain phospholipids of the awake rat, without changing turnover rates of docosahexaenoic or palmitic acid. Reduced AA turnover was accompanied by down-regulation of gene expression and protein levels of an AA-speci®c cytosolic phospholipase A 2 (cPLA 2 ). To see if VPA had the same effect on AA turnover, we used our in vivo fatty acid model in rats chronically administered VPA (200 mg/ kg, i.p. for 30 days). Like Li 1 , VPA treatment signi®cantly decreased AA turnover within brain phospholipids (by 28± 33%), although it had no effect on cPLA 2 protein levels. Thus, both mood stabilizers, Li 1 and VPA have a common action in reducing AA turnover in brain phospholipids, albeit by different mechanisms.

Alcoholism: Clinical and Experimental Research, 1997

Aging and chronic alcohol consumption can cause degenerative changes in the cerebellar cortex. In... more Aging and chronic alcohol consumption can cause degenerative changes in the cerebellar cortex. In this study, the effects of aging and lifelong alcohol consumption on cerebellar cortical layer volumes (molecular and granular) and also white matter layer volumes were studied in alcohol-preferring (AA) and nonpreferring (ANA) rats of both sexes. The ethanol-consuming animals (EtOH) had 12% (wlv) ethanol as the only available fluid from 4 to 22 months of age, whereas the young (3 month) and old controls (24 months) had only water to drink. The volumes of molecular, granular, and white matter layers of the cerebellar vermis in folia II, IV, VII, and X were measured by using systematic sampling and a point-counting method. The volumes of the granular and white matter layers showed consistent increase between 3 and 24 months of age, whereas the volume of the molecular layer remained unchanged with increasing age. Individual ethanol intake was measured over a 1-week period at the beginning and at the end of chronic ethanol exposure. Significant (ANOVA, p = 0.0oO) sex difference was found in the drinking behavior in both lines, with females consuming more alcohol than males (daily ethanol consumption at 22 months of age 3.2 f 0.3 vs. 7.1 f 0.3 glkg for AA males and females; 3.2 f 0.3 vs. 5.4 f 0.4 glkg for ANA males and females, respectively). The only ethanol-induced effect on the cerebellum was observed in ANA-EtOH females with a 15% reduction in the volumes of the molecular and granular layer in folium II compared with agematched controls and a significant ( p c 0.05, analysis of covariance with ethanol intake as a covariate) line difference in folium II (molecular and granular layers) was observed between ANA-EtOH females and AA-EtOH females. Furthermore, the volume of the molecular layer in folium II was significantly ( p c 0.05, analysis of covariance with ethanol intake and body weights as covariates) reduced for ANA-EtOH females, compared with ANA-EtOH males indicating a sex difference in the cerebellar degeneration due to chronic alcohol consumption. Of the three layers studied, the white matter layer was the most resistant layer to the effects caused by chronic alcohol consumption. In view of the fact that AA and ANA rats of both sexes differ regarding the drinking behavior and ethanol metabolism, they provide an important model for further research on ethanol-induced pathological changes in the central nervous system.