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Cellular and axonal diversity in molecular layer heterotopia of the rat cerebellar vermis.

ABSTRACT: Molecular layer heterotopia of the cerebellar primary fissure are a characteristic of many rat strains and are hypothesized to result from defect of granule cells exiting the external granule cell layer during cerebellar development. However, the cellular and axonal constituents of these malformations remain poorly understood. In the present report, we use histochemistry and immunocytochemistry to identify neuronal, glial, and axonal classes in molecular layer heterotopia. In particular, we identify parvalbumin-expressing molecular layer interneurons in heterotopia as well as three glial cell types including Bergmann glia, Olig2-expressing oligodendrocytes, and Iba1-expressing microglia. In addition, we document the presence of myelinated, serotonergic, catecholaminergic, and cholinergic axons in heterotopia indicating possible spinal and brainstem afferent projections to heterotopic cells. These findings are relevant toward understanding the mechanisms of normal and abnormal cerebellar development.

SUBMITTER: Van Dine SE

PROVIDER: S-EPMC3804155 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Cellular and axonal diversity in molecular layer heterotopia of the rat cerebellar vermis.

Van Dine Sarah E SE Salem Elsaid E George Elizabeth E Siu Nga Yan NY Dotzler Timothy T Ramos Raddy L RL

BioMed research international 20130926

Molecular layer heterotopia of the cerebellar primary fissure are a characteristic of many rat strains and are hypothesized to result from defect of granule cells exiting the external granule cell layer during cerebellar development. However, the cellular and axonal constituents of these malformations remain poorly understood. In the present report, we use histochemistry and immunocytochemistry to identify neuronal, glial, and axonal classes in molecular layer heterotopia. In particular, we iden ...[more]

PMID: 24191251

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Project description:Recent evidences suggest that cerebellar degeneration may be associated with the development of Alzheimer's disease (AD). However, previous reports were mainly observational, lacking substantial characterization of cellular and molecular cerebellar features during AD progression.This study is aimed at characterizing the cerebellum in rat models of AD and assessing the corresponding neuroprotective mechanisms of Garcinia biflavonoid complex (GBc).Male Wistar rats were grouped and treated alone or in combination with PBS (ad libitum)/day, corn oil (CO; 2 mL/kgBw/day), GBc (200 mg/kgBw/day), sodium azide (NaN3) (15 mg/kgBw/day) and aluminium chloride (AlCl3) (100 mg/kgBw/day). Groups A and B received PBS and CO, respectively; C received GBc; D received NaN3; E received AlCl3; F received NaN3 then GBc subsequently; G received AlCl3 then GBc subsequently; H received NaN3 and GBc simultaneously while I received AlCl3 and GBc simultaneously. Following treatments, cerebellar cortices were processed for histology, immunohistochemistry and colorimetric assays.Our data revealed that cryptic granule neurons and pyknotic Purkinje cell bodies (characterized by short dendritic/axonal processes) correspond to indistinctly demarcated cerebellar layers in rats treated with AlCl3 and NaN3. These correlates, with observed hypertrophic astrogliosis, increased the neurofilament deposition, depleted the antioxidant system-shown by expressed superoxide dismutase and glutathione peroxidase, and cerebellar glucose bioenergetics dysfunction-exhibited in assayed lactate dehydrogenase and glucose-6-phosphate dehydrogenase. We further showed that GBc reverses cerebellar degeneration through modulation of neurochemical signaling pathways and stressor molecules that underlie AD pathogenesis.Cellular, molecular and metabolic neurodegeneration within the cerebellum is associated with AlCl3 and NaN3-induced AD while GBc significantly inhibits corresponding neurotoxicity and is more efficacious when pre-administered.

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Dataset Information

Cellular and axonal diversity in molecular layer heterotopia of the rat cerebellar vermis.

Publications

Cellular and axonal diversity in molecular layer heterotopia of the rat cerebellar vermis.

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