Changes in Nitric Oxide Synthase Activities in the Cerebellum during Development and Aging of C57BL/6 Mice.

Abstract

Nitric oxide (NO) is one of the neurotransmitters in the cerebellum. Activities of NO synthase and densities of granule cells were determined in the cerebellum in an attempt to elucidate a mechanism of biochemical changes on the anatomical basis during aging. Activities of Cat+/calmoduline dependent NO synthase were measured in the cerebellum in male and female mice, from 18 gestation days to 28 months of age. There were significant differences in NO synthase activities among the groups of prenatal (18 gestation days), middle aged (5-18 months) and old aged (21-28 months) mice. Between groups of old and middle ages, a significant decrease with aging was found in the mean density of granular cells, which express NO synthase. Changes in NO synthase activities and granule cell densities occurred to a similar degree between old and middle ages. The present data suggest that an age-associated rise and fall of its activities likely occur in parallel with those of granule cell densities, and thus may represent impairment of cerebellar function during aging. NO synthase; cerebellum; development; aging Nitric oxide (NO) is a messenger molecule in many organs and systems (Bredt and Snyder 1992;Lowenstein and Snyder 1992;Snyder 1992). NO synthase generates NO and citrulline from arginine. Since NO has a very short half-life and is consumed immediately in situ after production, existence of NO synthase in a given micro environment is a predictor as to whether NO plays an important physiological role in it.Immunohistochemical and in situ hybridization studies have revealed that in the cerebellum, NO synthase localizes in granule and basket cells (Bredt et al. 1990). Its activity in the cerebellar cytosolic fraction in rats increased between 2 and 3 weeks after birth when granule cells migrate in the cerebellum (Matsumoto et al. 1993), suggesting that NO synthase activities in the cerebellum is a good marker of both anatomical and functional maturity of granule cells.

Brain Nitric Oxide and Its Dual Role in Neurodegeneration / Neuroprotection: Understanding Molecular Mechanisms to Devise Drug Approaches

“…Our own observation was that only striatum and olfactory cortex from aged rats showed a decrease in the activity and the expression of nNOS, but iNOS did not change in any of the considered areas [135]. Several other studies on aged animals have demonstrated regionally variable decrease of either catalytic activity or NOS expression/localization, with emerging discrepancies concerning the brain areas to which those alterations were located [234,[236][237][238][239]. Recently, it has been demonstrated that nNOS significantly decreases in the hippocampi from congnitively impaired aged rats only [240].…”

Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

“…There is a wealth of molecular and cellular phenomena, whose biological significance has been inferred experimentally, that could be incorporated into a realistic cerebellar model in order to investigate their implications for function. These include: the role of specific ionic channel properties in regulating neuronal excitation (amongst known examples see Jaeger et al, 1997 ; Bower and Beeman, 1998 ; Kubota and Bower, 2001 ; Ovsepian et al, 2013 ); the role of synaptic receptor properties in neuronal excitation and plasticity, like the voltage-dependence of NMDA receptor subtypes (Schwartz et al, 2012 ); the role of diffusible messengers like nitric oxide in coordinating long-term synaptic plasticity (Garthwaite, 2016 ); the role of intracellular biochemical cascades in the induction and expression of long-term synaptic plasticity (Tsukada et al, 1995 ; Schweighofer and Ferriol, 2000 ; Billings et al, 2014 ).…”

Differential expression of Na,K-ATPase ?-isoform mRNAs in aging rat cerebellum

“…Our finding of 84% declines in a3-mRNA content per PC supports a considerable alteration of some kind in neuronal activity before cell dropout. The 43% decline in granular cell a1-mRNA may be pertinent to the observed reduction in nitric oxide synthase (NOS) expression in granular cells (Tsukada et al, 1995) and the possible reduction in parallel fibers in the ML (Rogers et al, 1984). The reduced level of a1-mRNA may reflect a reduced granular cell activity that is critical to the level of activity in the PCs.…”