Phenotypical manifestations of partial trisomy 9 and monosomy 4 in two siblings

In this case report, we describe two siblings with a previously unreported partial monosomy 4q and partial trisomy 9q. The sibling karyotypes were determined to be 46,XX,der(4)t(4;9)(q33;q33)pat and 46,XY,der(4)t(4;9)-(q33;q33)pat. The siblings share several common pathological features, including VSD, PDA, low-set ears and digit anomalies as well as features consistent with Pierre-Robin syndrome and hydrocephalus. We review previously reported phenotypes associated with monosomy 4q and partial trisomy 9q and discuss potential mechanisms for these morphological insults with particular emphasis on neuropathology.     

The role of catecholamines in modulating responses to stress: Sex‐specific patterns,implications, and therapeutic potential for post‐traumatic stress disorder and opiate withdrawal

Emotional arousal is one of several factors that determine the strength of a memory and how efficiently it may be retrieved. The systems at play are multifaceted; on one hand, the dopaminergic mesocorticolimbic system evaluates the rewarding or reinforcing potential of a stimulus, while on the other, the noradrenergic stress response system evaluates the risk of threat, commanding attention, and engaging emotional and physical behavioral responses. Sex‐specific patterns in the anatomy and function of the arousal system suggest that sexually divergent therapeutic approaches may be advantageous for neurological disorders involving arousal, learning, and memory. From the lens of the triple network model of psychopathology, we argue that post‐traumatic stress disorder and opiate substance use disorder arise from maladaptive learning responses that are perpetuated by hyperarousal of the salience network. We present evidence that catecholamine‐modulated learning and stress‐responsive circuitry exerts substantial influence over the salience network and its dysfunction in stress‐related psychiatric disorders, and between the sexes. We discuss the therapeutic potential of targeting the endogenous cannabinoid system; a ubiquitous neuromodulator that influences learning, memory, and responsivity to stress by influencing catecholamine, excitatory, and inhibitory synaptic transmission. Relevant preclinical data in male and female rodents are integrated with clinical data in men and women in an effort to understand how ideal treatment modalities between the sexes may be different.     

Skewed T cell receptor V{alpha} repertoire among superantigen reactive murine T cells

Reactivity of murine T cells with viral or bacterial superantigensis clearly correlated with the expression of TCR V_ßdomains. Thus, T cells responding to the minor lymphocyte stimulatorylocus (Mls-1^a) or staphylococcal enterotoxin B (SEB) expresspredominantly TCR V_ß6 or V_ß8.2 respectively.We have investigated the involvement of the other major variableelement of the TCR, the V domain, in these superantigen responses.Using a panel of anti-TCR V mAbs, It is demonstrated that theTCR V repertoire among superantigen stimulated V_ß6⁺or V_ß8.2⁺ blasts (responding to Mls-1^a or SEB respectivelyin vitro) is altered in comparison with anti-CD3 stimulatedcells expressing the same V domains. Furthermore, the TCR Vrepertoire is strongly skewed in TCR V_ß8.2 transgenicmice that have undergone extensive peripheral clonal deletionafter SEB injection. These data imply that the V domain influencessuperantigen recognition by sthe TCR.     

No association between schizophrenia and homozygosity at the D3 dopamine receptor gene

The D₃ dopamine receptor gene is an important candidate gene for schizophrenia, since (because of its almost exclusive expression in the limbic system) it combines the dopamine receptor hypothesis with the limbic system hypothesis of schizophrenia. A BalI restriction fragment length polymorphism of the D₃ dopamine receptor gene has been typed in 107 schizophrenic patients and 98 normal controls from Sichuan (China). With regard to alleles or genotypes, no significant differences were obtained between controls from Europe and China, between patients and controls, and between patient subgroups and controls. These results indicate a lack of association between schizophrenia and the D₃ dopamine receptor gene in our sample. Our findings are at variance with reports of a significant excess of homozygosity at the D₃ dopamine receptor gene in schizophrenic patients from Wales (United Kingdom) and Alsace (France). In conclusion, further studies will be needed with larger samples of patients from Wales and Alsace as well as with samples of different racial groups to prove or disprove the initial positive association between schizophrenia and genotypes of the D₃ dopamine receptor gene. © 1993 Wiley-Liss, Inc.     

Absent chondrodysplasia punctata in a male with an Xp terminal deletion involving the putative region for CDPX1 locus

This is a follow-up report on a male patient with a 46, Y, r(X) karyotype. Although he had no clinico-radiological features of X-linked recessive chondrodysplasia punctata (CDPX1), molecular studies revealed an Xp terminal deletion involving the putative region for the CDPX1 locus (PABX-DXS31). We suspect that the absence of CDPX1 may be attributable to the nature of the disease and the extreme short stature of the patient (mean – 5.6 S.D.). © 1993 Wiley-Liss, Inc.     

Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

Neuromelanin-Sensitive Magnetic Resonance Imaging Changes in the Locus Coeruleus/Subcoeruleus Complex in Patients with Typical and Atypical Parkinsonism

Background

The locus coeruleus/subcoeruleus complex (LC/LsC) is a structure comprising melanized noradrenergic neurons.

Objective

To study the LC/LsC damage across Parkinson's disease (PD) and atypical parkinsonism in a large group of subjects.

Methods

We studied 98 healthy control subjects, 47 patients with isolated rapid eye movement sleep behavior disorder (RBD), 75 patients with PD plus RBD, 142 patients with PD without RBD, 19 patients with progressive supranuclear palsy (PSP), and 19 patients with multiple system atrophy (MSA). Twelve patients with MSA had proven RBD. LC/LsC signal intensity was derived from neuromelanin magnetic resonance imaging using automated software.

Results

The signal intensity was reduced in all parkinsonian syndromes compared with healthy control subjects, except in PD without RBD. The signal intensity decreased as age increased. Moreover, the signal intensity was lower in MSA than in isolated RBD and PD without RBD groups. In PD, the signal intensity correlated negatively with the percentage of REM sleep without atonia. There were no differences in signal intensity between PD plus RBD, PSP, and MSA.

Conclusions

Neuromelanin signal intensity was reduced in all parkinsonian disorders, except in PD without RBD. The presence of RBD in parkinsonian disorders appears to be associated with lower neuromelanin signal intensity. Furthermore, lower LC/LsC signal changes in PSP could be partly caused by the effect of age. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat

We have analyzed at high resolution the neuroanatomical connections of the juxtaparaventricular region of the lateral hypothalamic area (LHAjp); as a control and in comparison to this, we also performed a preliminary analysis of a nearby LHA region that is dorsal to the fornix, namely the LHA suprafornical region (LHAs). The connections of these LHA regions were revealed with a coinjection tract-tracing technique involving a retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracer. The LHAjp and LHAs together connect with almost every major division of the cerebrum and cerebrospinal trunk, but their connection profiles are markedly different and distinct. In simple terms, the connections of the LHAjp indicate a possible primary role in the modulation of defensive behavior; for the LHAs, a role in the modulation of ingestive behavior is suggested. However, the relation of the LHAjp and LHAs to potential modulation of these behaviors, as indicated by their neuroanatomical connections, appears to be highly integrative as it includes each of the major functional divisions of the nervous system that together determine behavior, i.e., cognitive, state, sensory, and motor. Furthermore, although a primary role is indicated for each region with respect to a particular mode of behavior, intermode modulation of behavior is also indicated. In summary, the extrinsic connections of the LHAjp and LHAs (so far as we have described them) suggest that these regions have a profoundly integrative role in which they may participate in the orchestrated modulation of elaborate behavioral repertoires.     

HYPOTHALAMIC DIGOXIN,HEMISPHERIC CHEMICAL DOMINANCE,AND MESENTERIC ARTERY OCCLUSION

The role of the isoprenoid pathway in vascular thrombosis, especially mesenteric artery occlusion and its relation to hemispheric dominance, was assessed in this study. The following parameters were measured in patients with mesenteric artery occlusion and individuals with right hemispheric, left hemispheric, and bihemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition. In patients with mesenteric artery occlusion there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, low ubiquinone, and elevated free radical levels. The RBC membrane Na+-K+ ATPase activity and serum magnesium were decreased. There was also an increase in tryptophan catabolites and reduction in tyrosine catabolites in the serum. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these patients. The biochemical patterns obtained in mesenteric artery occlusion is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with mesenteric artery occlusion were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Mesenteric artery occlusion occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function. Hemispheric chemical dominance may thus control the risk for developing vascular thrombosis in individuals     

Mapping a mouse limbic seizure susceptibility locus on chromosome 10

Purpose: Mapping seizure susceptibility loci in mice provides a framework for identifying potentially novel candidate genes for human epilepsy. Using C57BL/6J × A/J chromosome substitution strains (CSS), we previously identified a locus on mouse chromosome 10 (Ch10) conferring susceptibility to pilocarpine, a muscarinic cholinergic agonist that models human temporal lobe epilepsy by inducing initial limbic seizures and status epilepticus (status), followed by hippocampal cell loss and delayed‐onset chronic spontaneous limbic seizures. Herein we report further genetic mapping of pilocarpine quantitative trait loci (QTLs) on Ch10. Methods: Seventy‐nine Ch10 F₂ mice were used to map QTLs for duration of partial status epilepticus and the highest stage reached in response to pilocarpine. Based on those results we created interval‐specific congenic lines to confirm and extend the results, using sequential rounds of breeding selectively by genotype to isolate segments of A/J Ch10 genome on a B6 background. Key Findings: Analysis of Ch10 F₂ genotypes and seizure susceptibility phenotypes identified significant, overlapping QTLs for duration of partial status and severity of pilocarpine‐induced seizures on distal Ch10. Interval‐specific Ch10 congenics containing the susceptibility locus on distal Ch10 also demonstrated susceptibility to pilocarpine‐induced seizures, confirming results from the F₂ mapping population and strongly supporting the presence of a QTL between rs13480781 (117.6 Mb) and rs13480832 (127.7 Mb). Significance: QTL mapping can identify loci that make a quantitative contribution to a trait, and eventually identify the causative DNA‐sequence polymorphisms. We have mapped a locus on mouse Ch10 for pilocarpine‐induced limbic seizures. Novel candidate genes identified in mice can be investigated in functional studies and tested for their role in human epilepsy.