Phosphodiesterase and adenyl-cyclase activities in the cerebral cortex of the aging rat

Zimmerman, Irwin D.; Berg, A.

doi:10.1016/0047-6374(75)90010-x

Cited by 25 publications

(4 citation statements)

References 13 publications

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“…The cAMP-protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway mediates long-term neuronal plasticity and memory in various species from Aplysia ( Goelet et al, 1986 ; Bartsch et al, 1995 ) to mammals ( Florian et al, 2006 ; Brightwell et al, 2007 ; Ota et al, 2008 ). Because the physiological functions served by this pathway decrease in an age-dependent manner ( Zimmerman and Berg, 1975 ; Sugawa and May 1993 ; Karege et al, 2001 ), cAMP is likely an ideal molecule to target for the treatment of age-related memory impairment. Recently, strategies centering on the maintenance of pre-senescence cAMP levels have received much attention, with the goal of increasing the intracellular levels of cAMP in a spatiotemporally regulated manner upon memory formation ( Heckman et al, 2015 ; Yanai and Endo, 2019 ; Sanders and Rajagopal, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Reversal of spatial memory impairment by phosphodiesterase 3 inhibitor cilostazol is associated with reduced neuroinflammation and increased cerebral glucose uptake in aged male mice

et al. 2022

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The nucleotide second messenger 3′, 5′-cyclic adenosine monophosphate (cAMP) and 3′, 5′-cyclic guanosine monophosphate (cGMP) mediate fundamental functions of the brain, including learning and memory. Phosphodiesterase 3 (PDE3) can hydrolyze both cAMP and cGMP and appears to be involved in the regulation of their contents in cells. We previously demonstrated that long-term administration of cilostazol, a PDE3 inhibitor, maintained good memory performance in aging mice. Here, we report on studies aimed at determining whether cilostazol also reverses already-impaired memory in aged male mice. One month of oral 1.5% cilostazol administration in 22-month-old mice reversed age-related declines in hippocampus-dependent memory tasks, including the object recognition and the Morris water maze. Furthermore, cilostazol reduced neuroinflammation, as evidenced by immunohistochemical staining, and increased glucose uptake in the brain, as evidence by positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). These results suggest that already-expressed memory impairment in aged male mice that depend on cyclic nucleotide signaling can be reversed by inhibition of PDE3. The reversal of age-related memory impairments may occur in the central nervous system, either through cilostazol-enhanced recall or strengthening of weak memories that otherwise may be resistant to recall.

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Section: Introductionmentioning

confidence: 99%

Reversal of spatial memory impairment by phosphodiesterase 3 inhibitor cilostazol is associated with reduced neuroinflammation and increased cerebral glucose uptake in aged male mice

et al. 2022

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“…Zimmermann and Berg (15) demonstrated that the kinetic parameters as well as the activities of adenyl cyclase and PE in rat brain cortex are not changed during the lifetime of the animal (24 months). However, these authors have recently demonstrated (16) an age-dependent influence on the low-Km PE of an endogenous activator protein, described in detail by Cheung (3).…”

Section: Different Investigators Such As De Robertis Et Al (4) Flormentioning

confidence: 99%

The Influence of Dihydroergotoxine Mesylate on the Low-K Phosphodiesterase of Cat and Rat Brain <i>in vitro</i>

Enz¹,

Iwangoff²,

Chappuis³

1978

Gerontology

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Dihydroergotoxine mesylate (DHET; active substance of Hydergine®) was shown to be a stronger inhibitor of the low-K_m than of the high-K_m phosphodiesterase (PE) in cat and rat brain homogenates. The inhibition due to DHET was greater when a purified low-K_m PE preparation originating from a sonicated pellet (100,000 ¿r) of rat brain tissue was used. The drug alters the kinetic properties of the enzyme, producing a lowering of the negative cooperativity effect. This kind of PE inhibition is of particular importance at normal cellular cAMP levels, but does not interfere with cAMP production by hormonal stimulation.

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“…and cyclic nucleotide levels iir i.ii.0 a r e unchanged in almost all regions of the aged brain (Schmidt et al, 1979ti). Cyclic AMPdegradation is also unaffected by aging (Zimmerman and Berg, 1975;Puri and Volicer, 1977). The phosphorylating system in the brain also appears stable in senescence, a s evidenced by substantial cyclic AMP-dependent protein kinase and phosphoprotein phosphatase activities in the brains of aged rats (Schmidt et al, 1980).…”

mentioning

confidence: 99%

Cyclic AMP‐Dependent Protein Kinase Activity in Human Brain Across Age

Schmidt¹,

Truex²,

Ghetti

et al. 1980

Journal of Neurochemistry

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Cyclic AMP-dependent protein kinase activity was measured in the cerebral cortex of humans 2 days to 83 years of age and in the cortex of F344 rats 3, 22, or 30 months of age. Protein kinase activity was detected in the human brain, but no age-related differences in activity were observed in the presence or absence of cyclic AMP. Age differences were also not seen in protein kinase in the rat cerebral cortex. Enzyme activities in rat and human brain were similar.

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Phosphodiesterase and adenyl-cyclase activities in the cerebral cortex of the aging rat

Cited by 25 publications

References 13 publications

Reversal of spatial memory impairment by phosphodiesterase 3 inhibitor cilostazol is associated with reduced neuroinflammation and increased cerebral glucose uptake in aged male mice

Reversal of spatial memory impairment by phosphodiesterase 3 inhibitor cilostazol is associated with reduced neuroinflammation and increased cerebral glucose uptake in aged male mice

The Influence of Dihydroergotoxine Mesylate on the Low-K Phosphodiesterase of Cat and Rat Brain <i>in vitro</i>

Cyclic AMP‐Dependent Protein Kinase Activity in Human Brain Across Age

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