Morphological alterations in neocortical and cerebellar GABAergic neurons in a canine model of juvenile Batten disease

P. A. March, S. Wurzelmann, Steven U. Walkley

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The pathogenesis of brain dysfunction in a canine model of juvenile Batten disease was studied with techniques designed to determine sequential changes in mitochondrial morphology and cytochrome oxidase (CO) activity, and in neurons and synapses using gamma-aminobutyric acid (GABA) as a neurotransmitter. Histochemical and immunocytochemical methods were employed. Mitochondrial alterations were found in a select population of nonpyramidal neurons in neocortex and claustrum, and in cerebellar basket cells. Proportions of affected neurons at any one time remained constant over the disease course, with morphologically-abnormal mitochondria first being recognized at age 6 months. Enlarged mitochondria were readily identifiable at the light microscope (LM) level as large CO-positive or mitochondrial antibody-positive granular structures. Colabelling with antibodies to GABA or to parvalbumin (PV) indicated that most of these cells were GABAergic. Ultrastructurally, atypical mitochondria were characterized by globular enlargement, intramitochondrial membranous inclusions, and disorganized internal structure. CO activity in all other cell somata and in neuropil was diminished compared with normal, age-matched tissue. Glutamic acid decarboxylase (GAD), PV, and GABA studies demonstrated loss of GABAergic neurons and synapses in cortex and cerebellum of affected dogs. These results indicate that abnormal mitochondria are present in neurons in Batten disease, and suggest that suboptimal mitochondrial function may play a role in the pathogenic mechanisms of brain dysfunction in this disorder.

Original languageEnglish (US)
Pages (from-to)204-212
Number of pages9
JournalAmerican Journal of Medical Genetics
Volume57
Issue number2
DOIs
StatePublished - 1995

Fingerprint

Neuronal Ceroid-Lipofuscinoses
GABAergic Neurons
Canidae
Mitochondria
Electron Transport Complex IV
gamma-Aminobutyric Acid
Neurons
Parvalbumins
Synapses
Glutamate Decarboxylase
Neuropil
Antibodies
Neocortex
Brain
Carisoprodol
Basal Ganglia
Cerebellum
Neurotransmitter Agents
Dogs
Light

Keywords

  • canine
  • cytochrome oxidase
  • GABA
  • immunocytochemistry
  • lysosomal storage disease
  • mitochondria

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Morphological alterations in neocortical and cerebellar GABAergic neurons in a canine model of juvenile Batten disease. / March, P. A.; Wurzelmann, S.; Walkley, Steven U.

In: American Journal of Medical Genetics, Vol. 57, No. 2, 1995, p. 204-212.

Research output: Contribution to journalArticle

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