title: The number of Purkinje neurons and their topology in the cerebellar vermis of normal and reln haplodeficient mouse.
abstract: The Reeler heterozygous mice (reln(+/-)) are haplodeficient in the gene (reln) encoding for the reelin glycoprotein (RELN) and display reductions in brain/peripheral RELN similar to autistic or schizophrenic patients. Cytoarchitectonic alterations of the reln(+/-) brain may be subtle, and are difficult to demonstrate by current histological approaches. We analyzed the number and topological organization of the Purkinje neurons (PNs) in five vermal lobules - central (II-III), culmen (IV-V), tuber (VIIb), uvula (IX), and nodulus (X) - that process different types of afferent functional inputs in reln(+/+) and reln(+/-) adult mice (P60) of both sexes (n=24). Animals were crossed with L7GFP mice so that the GFP-tagged PNs could be directly identified in cryosections. Digital images from these sections were processed with different open source software for quantitative topological and statistical analyses. Diversity indices calculated were: maximum caliper, density, area of soma, dispersion along the XZ axis, and dispersion along the YZ axis. We demonstrate: i. reduction in density of PNs in reln(+/-) males (14.37%) and reln(+/-) females (17.73%) compared to reln(+/+) males; ii. that reln(+/-) males have larger PNs than other genotypes, and females (irrespective of the reln genetic background) have smaller PNs than reln(+/+) males; iii. PNs are more chaotically arranged along the YZ axis in reln(+/-) males than in reln(+/+) males and, except in central lobulus, reln(+/-) females. Therefore, image processing and statistics reveal previously unforeseen gender and genotype-related structural differences in cerebellum that may be clues for the definition of novel biomarkers in human psychiatric disorders.
authors.affiliation: University of Pisa, Research Center E. Piaggio, Faculty of Engineering, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Magliaro
authors.affiliation: University of Turin, Department of Veterinary Sciences, Turin, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Cocito
authors.affiliation: University of Turin, Department of Veterinary Sciences, Turin, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bagatella
authors.affiliation: University of Turin, Department of Veterinary Sciences, Turin, Italy.
authors.forename: Adalberto
authors.initials: A
authors.lastname: Merighi
authors.affiliation: University of Pisa, Research Center E. Piaggio, Faculty of Engineering, Pisa, Italy.
authors.forename: Arti
authors.initials: A
authors.lastname: Ahluwalia
authors.affiliation: University of Turin, Department of Veterinary Sciences, Turin, Italy. Electronic address: laura.lossi@unito.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Lossi
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002452:Cell Count; D002526:Cerebellar Diseases / Q000235:genetics* / Q000473:pathology*; D065814:Cerebellar Vermis / Q000473:pathology* / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006239:Haplotypes / Q000235:genetics; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011689:Purkinje Cells / Q000473:pathology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D012737:Sex Factors
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: Cerebellum; Gender; Neurological disorder; Purkinje cells; Reeler