Midbrain-hindbrain involvement in lissencephalies
NEUROLOGY
Authors: Jissendi-Tchofo, Patrice; Kara, Simay; Barkovich, A. James
Abstract
Objectives: To determine the involvement of the midbrain and hindbrain (MHB) in the groups of classic (cLIS), variant (vLIS), and cobblestone complex (CBSC) lissencephalies and to determine whether a correlation exists between the cerebral malformation and the MHB abnormalities. Methods: MRI scans of 111 patients (aged 1 day to 32 years; mean 5 years 4 months) were retrospectively reviewed. After reviewing the brain involvement on MRI, the cases were reclassified according to known mutation (LIS1, DCX, ARX, VLDLR, RELN, MEB, WWS) or mutation phenotype (LIS1-P, DCX-P, RELN-P, ARX- P, VLDLR-P) determined on the basis of characteristic MRI features. Abnormalities in the MHB were then recorded. For each structure, a score was assigned, ranging from 0 (normal) to 3 (severely abnormal). The differences between defined groups and the correlation between the extent of brain agyria/pachygyria and MHB involvement were assessed using Kruskal-Wallis and chi(2) McNemar tests. Results: There was a significant difference in MHB appearance among the three major groups of cLIS, vLIS, and CBSC. The overall score showed a severity gradient of MHB involvement: cLIS (0 or 1), vLIS (7), and CBSC (11 or 12). The extent of cerebral lissencephaly was significantly correlated with the severity of MHB abnormalities (p = 0.0029). Conclusion: Our study focused on posterior fossa anomalies, which are an integral part of cobblestone complex lissencephalies but previously have not been well categorized for other lissencephalies. According to our results and the review of the literature, we propose a new classification of human lissencephalies. Neurology (R) 2009;72:410-418
Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons
MOLECULAR METABOLISM
Authors: Roberts, Brandon L.; Bennett, Baylin J.; Bennett, Camdin M.; Carroll, Julie M.; Dalboge, Louise S.; Hall, Colin; Hassouneh, Wafa; Heppner, Kristy M.; Kirigiti, Melissa A.; Lindsley, Sarah R.; Tennant, Katherine G.; True, Cadence A.; Whittle, Andrew; Wolf, Anitra C.; Roberts, Charles T., Jr.; Tang-Christensen, Mads; Sleeman, Mark W.; Cowley, Michael A.; Grove, Kevin L.; Kievit, Paul
Abstract
Objective: Reelin (RELN) is a large glycoprotein involved in synapse maturation and neuronal organization throughout development. Deficits in RELN signaling contribute to multiple psychological disorders, such as autism spectrum disorder, schizophrenia, and bipolar disorder. Nutritional stress alters RELN expression in brain regions associated with these disorders; however, the involvement of RELN in the neural circuits involved in energy metabolism is unknown. The RELN receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are involved in lipid metabolism and expressed in the hypothalamus. Here we explored the involvement of RELN in hypothalamic signaling and the impact of diet-induced obesity (DIO) on this system. Methods: Adult male mice were fed a chow diet or maintained on a high-fat diet (HFD) for 12-16 weeks. HFD-fed DIO mice exhibited decreased ApoER2 and VLDLR expression and increased RELN protein in the hypothalamus. Electrophysiology was used to determine the mechanism by which the central fragment of RELN (CF-RELN) acts on arcuate nucleus (ARH) satiety-promoting proopiomelanocortin (POMC) neurons and the impact of DIO on this circuitry. Results: CF-RELN exhibited heterogeneous presynaptic actions on inhibitory inputs onto ARH-POMC-EGFP neurons and consistent postsynaptic actions. Additionally, central administration of CF-RELN caused a significant increase in ARH c-Fos expression and an acute decrease in food intake and body weight. Conclusions: We conclude that RELN signaling is modulated by diet, that RELN is involved in synaptic signaling onto ARH-POMC neurons, and that altering central CF-RELN levels can impact food intake and body weight. (C) 2019 The Authors. Published by Elsevier GmbH.