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Background: Fractalkine (CX3CL1; FKN) is a chemokine expressed by neurons that mediates communication between neurons and microglia. By regulating microglial activity, CX3CL1 can mitigate the damaging effects of chronic microglial inflammation within the brain, a state that plays a major role in aging and neurodegeneration. CX3CL1 is present in two forms, a full-length membrane-bound form and a soluble cleaved form (sFKN), generated by a disintegrin and metalloproteinase (ADAM) 10 or 17. Levels of sFKN decrease with aging, which could lead to enhanced inflammation, deficits in synaptic remodeling, and subsequent declines in cognition. Recently, the idea that these two forms of CX3CL1 may display differential activities within the CNS has garnered increased attention, but remains unresolved., Methods: Here, we assessed the consequences of CX3CL1 knockout (CX3CL1 -/- ) on cognitive behavior as well as the functional rescue with the two different forms of CX3CL1 in mice. CX3CL1 -/- mice were treated with adeno-associated virus (AAV) expressing either green fluorescent protein (GFP), sFKN, or an obligate membrane-bound form of CX3CL1 (mFKN) and then subjected to behavioral testing to assess cognition and motor function. Following behavioral analysis, brains were collected and analyzed for markers of neurogenesis, or prepared for electrophysiology to measure long-term potentiation (LTP) in hippocampal slices., Results: CX3CL1 -/- mice showed significant deficits in cognitive tasks for long-term memory and spatial learning and memory in addition to demonstrating enhanced basal motor performance. These alterations correlated with deficits in both hippocampal neurogenesis and LTP. Treatment of CX3CL1 -/- mice with AAV-sFKN partially corrected changes in both cognitive and motor function and restored neurogenesis and LTP to levels similar to wild-type animals. Treatment with AAV-mFKN partially restored spatial learning and memory in CX3CL1 -/- mice, but did not rescue long-term memory, or neurogenesis., Conclusions: These results are the first to demonstrate that CX3CL1 knockout causes significant cognitive deficits that can be rescued by treatment with sFKN and only partially rescued with mFKN. This suggests that treatments that restore signaling of soluble forms of CX3CL1 may be a viable therapeutic option for aging and disease.

Chromatography of brain and liver 100,000 g supernatants over HPLC molecular sieve columns revealed striking differences in the molecular weight distribution of ATP-sulfurylase and APS-kinase of the two tissues, pointing to different enzymic species for both enzymes in brain and liver. This was further substantiated by kinetic characterization of the two enzymes of both tissues. APS-kinase of liver is allosterically activated by ATP, while the brain enzyme is not. ATP-sulfurylase of brain is activated at high, but still physiological concentrations of ATP. Brain ATP-sulfurylase is inhibited by phenylalanine.

The ultrasonographic image of the fetal head at the appropriate level for determination of the biparietal diameter reveals an apparent asymmetry of the cerebral hemispheres. This was confirmed and analyzed in 49 sequential fetuses who had no neurologic deficits at birth and in the autopsy specimen of an 8-month-old infant without any anatomic abnormalities of the head. In the hemisphere farthest from the transducer, a crescent-shaped echo-poor region was visualized abutting the calvarium. This resembles an abnormal fluid collection but represents normal anatomy. High-amplitude reflections were observed on the medial side of the crescent and were produced by the combination of the sylvian fissure and the choroid plexus of the lateral ventricle. The fine echo pattern of the near hemisphere, which appeared to represent normal anatomy, was artifactual. The cerebral asymmetry seen by conventional ultrasonographic imaging after the 15th gestational week should not suggest an underlying pathologic process. The studies suggest that a higher-quality examination of the near hemisphere of the fetal cranium can be performed with properly focused transducers.

A sensitive and rapid assay method method for cysteic acid decarboxylase was develped which combined the selectivity of ion exchange resin (a complete retention of the substrate, cysteic acid, and exclusion of the product, taurine) with the speed of a vacuum filtration. The synthesis and purification of 35S-labeled cysteic acid were described. The validity of the assay was established by the identification of the reaction product as taurine. With this new method, the decarboxylase activity was measured in discrete regions of bovine brain. Putamen had the highest activity, 172 pmol taurine formed/min/mg protein (100%), followed by caudate nucleus, 90%; cerebral cortex, 82%; hypothalamus, 81%; cerebellar cortex, 79%; cerebellar peduncle, 59%; thalamus, 42%; brain stem, 25%; pons, 10%; and corpus callosum, 3%. The decarboxylase activity in various mouse tissues was also determined as follows: liver, 403; brain, 145; kidney, 143; spinal cord, 59; lung, 21; and spleen, 10 pmol taurine formed/min/mg. No activity could be detected in skeleton muscle and heart, suggesting a different biosynthetic pathway for taurine synthesis in these tissues. The advantages and disadvantages of the new assay method are also discussed.

The development of the enzymes of sulfate activation, ATP-sulfurylase and APS-kinase has been studied in rat cerebrum and, for comparison, in rat liver as well. Cerebrum contains a species of ATP-sulfurylase which can be inhibited by phenylalanine. The activity of this form of ATP-sulfurylase is high in oligodendroglial cells and parallels the rate of myelination.