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In order to detect the two splice variant forms of type-IVB cyclic AMP phosphodiesterase (PDE) activity, DPD (type-IVB1) and PDE-4 (type-IVB2), anti-peptide antisera were generated. One set (‘DPD/PDE-4-common’), generated against a peptide sequence found at the common C-terminus of these two PDEs, detected both PDEs. A second set was PDE-4 specific, being directed against a peptide sequence found within the unique N-terminal region of PDE-4. In brain, DPD was found exclusively in the cytosol and PDE-4 exclusively associated with membranes. Both brain DPD and PDE-4 activities, isolated by immunoprecipitation, were cyclic AMP-specific (KmcyclicAMP: approximately 5 microM for DPD; approximately 4 microM for PDE-4) and were inhibited by low rolipram concentrations (K1rolipram approximately 1 microM for both). Transient expression of DPD in COS-1 cells allowed identification of an approx. 64 kDa species which co-migrated on SDS/PAGE with the immunoreactive species identified in both brain cytosol and membrane fractions using the DPD/PDE-4-common antisera. The subunit size observed for PDE-4 (approx. 64 kDa) in brain membranes was similar to that predicted from the cDNA sequence, but that observed for DPD was approx. 4 kDa greater. Type-IV, rolipram-inhibited PDE activity was found in all brain regions except the pituitary, where it formed between 30 and 70% of the PDE activity in membrane and cytosolic fractions when assayed with 1 microM cyclic AMP, PDE-4 formed 40-50% of the membrane type-IV activity in all brain regions save the midbrain (approx. 20%). DPD distribution was highly restricted to certain regions, providing approx. 35% of the type-IV cytosolic activity in hippocampus and 13-21% in cortex, hypothalamus and striatum with no presence in brain stem, cerebellum, midbrain and pituitary. The combined type-IVB PDE activities of DPD and PDE-4 contributed approx. 10% of the total PDE activity in most brain regions except for the pituitary (zero) and the mid-brain (approx. 3%. The isolated cDNAs for DPD and PDE-4 appear to reflect transcription products which are expressed in vivo in brain. The unique N-terminal domain of PDE-4 is suggested to target this PDE to membranes in brain. Type-IVB PDEs are differentially expressed in various brain regions, indicating that there are tissue-specific controls on both the expression of the gene and the splicing of its products.

Speech and language-related functions tend to depend on the left hemisphere more than the right in most right-handed (dextral) participants. This relationship is less clear in non-right handed (adextral) people, resulting in surprisingly polarised opinion on whether or not they are as lateralised as right handers. The present analysis investigates this issue by largely ignoring methodological differences between the different neuroscientific approaches to language lateralization, as well as discrepancies in how dextral and adextral participants were recruited or defined. Here we evaluate the tendency for dextrals to be more left hemisphere dominant than adextrals, using random effects meta analyses. In spite of several limitations, including sample size (in the adextrals in particular), missing details on proportions of groups who show directional effects in many experiments, and so on, the different paradigms all point to proportionally increased left hemispheric dominance in the dextrals. These results are analysed in light of the theoretical importance of these subtle differences for understanding the cognitive neuroscience of language, as well as the unusual asymmetry in most adextrals.

The neuropeptide galanin is implicated in regulation of affective behavior, including modulation of 5-HT signaling. Here, we investigated, by use of microdialysis in freely moving rats, the effects of intracerebral (i.c.) and intracerebroventricular (i.c.v.) infusions of galanin on basal extracellular 5-HT levels in medial prefrontal cortex (mPFC), CA1 area of ventral hippocampus (vHPC), central amygdaloid nucleus (CeA), ventromedial hypothalamic nucleus ventrolateral part (VMHvl), and ventromedial caudate putamen (CPu). These results were compared with a parallel immunohistochemical analysis of the distribution of galanin, 5-HT, and noradrenaline (NA) nerve terminals, and with data on galanin receptors. Galanin i.c.v. significantly decreased the 5-HT levels in mPFC to 79% and in vHPC to 72%. Local infusions of galanin caused a long-lasting decrease in 5-HT levels in vHPC to 88%, and a moderate decrease in CeA, whereas the 5-HT levels in mPFC significantly increased to 121%. These effects of i.c. galanin correlated well with the density of 5-HT and galanin nerve terminals and galanin receptors autoradiography in mPFC, vHPC, and CeA. No effects of i.c. or i.c.v. galanin on 5-HT levels were observed in CPu or VMHvl, in agreement with the low numbers of galanin-positive terminals and low/moderate galanin receptor density. Galanin was often found to coexist in NA, but could never be detected in 5-HT terminals. Together the results show a neuroanatomical correlation between the effects of galanin infusions on 5-HT release and distribution of galanin and its receptors, and that i.c.v. and i.c. administration can give opposite effects on 5-HT release.

© 2020, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Purpose of Review: This paper aims to review novel trends in cholinergic neuroimaging in Alzheimer and Lewy body parkinsonian disorders. Recent Findings: The spectrum of cholinergic imaging is expanding with the availability of spatially more precise radioligands that allow assessment of previously less recognized subcortical and cortical structures with more dense cholinergic innervation. In addition, advances in MRI techniques now allow quantitative structural or functional assessment of both the cholinergic forebrain and the pedunculopontine nucleus, which may serve as non-invasive prognostic predictors. Multimodal imaging approaches, such as PET-MRI or multiligand PET, offer new insights into the dynamic and interactive roles of the cholinergic system at both local and larger-scale neural network levels. Summary: Our understanding of the heterogeneous roles of the cholinergic system in age-related diseases is evolving. Multimodal imaging approaches that provide complimentary views of the cholinergic system will be necessary to shed light on the impact of cholinergic degeneration on regional and large-scale neural networks that underpin clinical symptom manifestation in neurodegeneration.

Neuroimaging is traditionally divided into structural and functional imaging. Structural imaging looks at brain structure or anatomy and includes computed tomography (CT) and magnetic resonance imaging (MRI). Functional techniques seek to examine the physiological functioning of the brain, either at rest or during activation, and include single photon emission computed tomography (SPECT), positron emission tomography (PET), MRI spectroscopy, functional MRI (fMRI) and encephalographic brain mapping. Although fMRI, MRI spectroscopy and brain mapping are likely to have clinical applications in the near future, the main imaging modalities of current clinical relevance to psychiatrists are CT, MRI and SPECT, which will be the focus of this article.

We evaluated the detection of gastric varices, inflowing blood vessels to gastric varices, and outflowing blood vessels from gastric varices via magnetic resonance (MR) angiography in 31 patients with gastric varices. Twenty-four patients had F2 type varices and 7 had F3 type, classified according to the Japanese Research Society for Portal Hypertension. Seventeen patients had cardiofornical varices, and 14 had fundal varices. All patients were examined with an MR system operating at 1.5T. MR angiography was performed using the two-dimensional time-of-flight method. With MR angiography, the imaging of gastric varices was clearly delineated in 28 of the 31 patients (90.3%). From the images of MR angiography, flow direction itself cannot be determined. The outflowing blood vessels of gastric varices were reported to be the gastro-renal shunt and the subphrenic vein, and angiographic findings have shown the inflowing blood vessels to be the left gastric vein (LGV), the short gastric vein (SGV), and the posterior gastric vein (PGV). In 25 of the 31 patients (80.7%), the outflowing blood vessels from gastric varices were detected (gastro-renal shunt in 24; subphrenic vein in 1). MR angiography provided clear images of the inflowing blood vessels to gastric varices in 18 of the 31 patients (58.1%). These inflowing vessels were categorized as SGV in 7 patients, LGV in 5, LGV and SGV in 4, and LGV and PGV in 2. We suggest that MR angiography be used as a routine method for detecting and diagnosing collateral veins in patients with gastric varices.