Regional alterations of the NO/NOS system in the aging brain: a biochemical, histochemical and immunochemical study in the rat

Necchi, Daniela; Virgili, Marco; Monti, Barbara; Contestabile, Antonio; Scherini, Elda

doi:10.1016/s0006-8993(02)02302-8

Cited by 47 publications

(37 citation statements)

References 44 publications

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“…Although the present findings generally appear to support the potential involvement of NOS/NO in brain aging, we question the potential contribution of iNOS to normal aging. Given the increasing evidence that NO plays an important role in the neurodegenerative process (for review, see Law et al, 2001), together with the results of Necchi et al (2002), the current findings suggest that NO may contribute differently to the normal physiological and pathological aspects of the aging process. Finally, our ageassociated changes in arginase have raised a novel issue of a possible contribution of this enzyme to aging.…”

Section: Age-related Changes In Nos and Arginase Activitymentioning

confidence: 61%

“…In contrast to the positive findings described above, it has recently been shown that there is a decreased number of NOS neurons in the aged hippocampus (Cha et al, 1998;Necchi et al, 2002). In addition, a parallel relationship between the decrement of NO production and the reduction of long-term potentiation in the aged hippocampus has also been reported (Mori et al, 2000).…”

Section: Age-related Changes In Nos and Arginase Activitymentioning

confidence: 82%

“…During the past few years, changes in NO in the hippocampus that occur during normal aging have received much attention. It has been demonstrated, for example, that the activity and/or mRNA expression of nNOS and iNOS protein expression increased significantly in the aged hippocampus (Sugaya et al, 1996;La Porta and Comolli, 1999;Law et al, 2000Law et al, , 2002, although a decreased number of NOS containing neurons and a decreased nNOS protein expression have also been reported (Cha et al, 1998;Law et al, 2002;Necchi et al, 2002). The observation of a correlation between changes in nNOS mRNA expression in the hippocampus and age-related cognitive impairments has provided strong support for the contribution of NO to the aging process (Sugaya et al, 1996;Law et al, 2000).…”

Section: Introductionmentioning

confidence: 95%

“…It has been proposed that NO is increased in the aged brain and that inducible nitric oxide synthase (iNOS) is likely to be responsible for the increased NO (McCann, 1997;McCann et al, 1998). Consistent with this hypothesis, it has been shown that there are increases in the number of NOS containing neurons, in NOS activity, and in mRNA and protein expression of neuronal nitric oxide synthase (nNOS) and/or iNOS in the aged brain (Sugaya et al, 1996;Uttenthal et al, 1998;Vernet et al, 1998;La Porta and Comolli, 1999;Cha et al, 2000;Law et al, 2000Law et al, , 2002, although some conflicting results have also been reported (Yamada et al, 1996;Cha et al, 1998;Yu et al, 2000;Necchi et al, 2002).…”

Section: Introductionmentioning

confidence: 98%

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Nitric oxide synthase and arginase in the rat hippocampus and the entorhinal, perirhinal, postrhinal, and temporal cortices: Regional variations and age‐related changes

et al. 2003

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Increasing evidence suggests that nitric oxide synthase (NOS)/nitric oxide (NO) contributes to the aging process. By contrast, the role of arginase, which shares a common substrate with NOS, has not been determined. In the present study, regional variations and age-related changes in NOS and arginase in the hippocampus and its neighboring structures were investigated for the first time. In young adult rats, high levels of NOS activity were found in the entorhinal, perirhinal, and postrhinal cortices, whereas low values were located in the hippocampus and the temporal cortex. Interestingly, arginase activity showed an overall inverse pattern with the lowest levels in the entorhinal and perirhinal cortices. When a comparison was carried out between young (4-month-old) and aged (24-month-old) rats, significant increases in total NOS activity were found in the aged entorhinal and temporal cortices, and a significant decrease in arginase activity was observed in the aged postrhinal cortex. Western blotting demonstrated significant decreases in both neuronal and endothelial NOS expression in the aged hippocampus and postrhinal cortex, whereas arginase I and II expression did not show age-related changes in any region examined. Activity and protein expression of inducible NOS were not detected in any tissue from either group. The present findings of region-specific changes in NOS and arginase appear to support the potential involvement of NOS/NO in the aging process and raise the issue of a possible contribution of arginase to aging.

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Section: Age-related Changes In Nos and Arginase Activitymentioning

confidence: 61%

Section: Age-related Changes In Nos and Arginase Activitymentioning

confidence: 82%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Nitric oxide synthase and arginase in the rat hippocampus and the entorhinal, perirhinal, postrhinal, and temporal cortices: Regional variations and age‐related changes

et al. 2003

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“…The experimental protocols were approved by a local bioethical committee, and the experiments were performed under the supervision of a veterinary commission. The age-related neurochemical alterations of these animals have been extensively studied from our group during the last few years (Virgili et al, 2001a,b;Necchi et al, 2002;.…”

Section: Subjectsmentioning

confidence: 99%

Dysregulation of memory-related proteins in the hippocampus of aged rats and their relation with cognitive impairment

2005

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In the present experiments, we used conditioned fear to study whether changes in expression or functional state of proteins known to be involved in hippocampal learning could suggest correlation with age-related memory deficits. We focused on both alterations constitutively present in the hippocampus of aged rats and alterations related to different learning responses. Our results point at the dysregulation of the phosphorylation state of CREB in the hippocampus of aged rats as a primary biochemical correlate of their impaired memory. Other proteins, known to be important for various steps of memory formation and consolidation and linked to CREB, are to some extent altered in their constitutive expression or in the response to learning in the aged hippocampus. In particular, phosphorylated CREB and Arc, a protein functionally related to CREB in memory consolidation, are both present at constitutively higher levels in the hippocampus of aged rats, but they are not susceptible to the learning-related up-regulation occurring in young adults. Two other CREB-regulated proteins involved in memory consolidation, the neurotrophin BDNF and the transcription factor C/EBPbeta, are expressed at similar levels in the hippocampus of young-adult and aged rats, but their response to conditioned fear learning appears dysregulated by aging. Calcineurin, a protein phosphatase having CREB among its substrates and whose expression negatively correlates with learning, is more expressed in the hippocampus of aged rats. However, while calcineurin expression decreases in the hippocampus of young adults after learning, no changes are observed in the hippocampus of aged, learning-impaired rats.

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Hippocampal nitric oxide synthase and arginase and age-associated behavioral deficits

et al. 2005

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The present study investigated age-related changes in nitric oxide synthase (NOS) and arginase in the subregions of the hippocampus and their correlations with animals' performance in the open field, T-maze, and water maze tasks. Aged rats (24 months old) showed reduced exploratory activity and poorer spatial learning relative to the young adults (4 months old). Significant increases in total NOS activity were found in the aged dentate gyrus and a dramatic decrease in endothelial NOS expression was observed in the aged CA2/3. Activity or protein expression of inducible NOS was not detected in any subregion of the hippocampus. There were no age-related changes in total arginase activity or arginase I and arginase II protein expression. Correlation analysis revealed that animals' motor ability was associated with CA1 NOS and arginase, as well as hippocampal function. The present findings provide further support for the involvement of NOS/NO and arginase in the normal aging process. A strong positive correlation between CA1 eNOS protein expression and swimming speed in the water maze task may reflect a relationship between the local cerebral blood flow and neuronal activity.

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Regional alterations of the NO/NOS system in the aging brain: a biochemical, histochemical and immunochemical study in the rat

Cited by 47 publications

References 44 publications

Nitric oxide synthase and arginase in the rat hippocampus and the entorhinal, perirhinal, postrhinal, and temporal cortices: Regional variations and age‐related changes

Nitric oxide synthase and arginase in the rat hippocampus and the entorhinal, perirhinal, postrhinal, and temporal cortices: Regional variations and age‐related changes

Dysregulation of memory-related proteins in the hippocampus of aged rats and their relation with cognitive impairment

Hippocampal nitric oxide synthase and arginase and age-associated behavioral deficits

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