title: Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis.
abstract: The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited neurodegenerative diseases. Sheep affected with the CLN6 form provide a valuable model to investigate underlying disease mechanisms from preclinical stages. Excitatory neuron loss in these sheep is markedly regional, localized early reactive changes accurately predicting neuron loss and subsequent symptom development. This investigation of GABAergic interneuron loss revealed similar regional effects that correlate with symptoms. Loss of parvalbumin positive neurons from the affected cortex was apparent at four months and became profound by 19 months, as was somatostatin positive neuron loss to a lesser extent. Conversely calbindin and neuropeptide Y positive neurons were relatively preserved and calretinin staining temporarily increased. Staining of subcortical regions was more intense but subcortical architecture remained relatively intact. Discrete subcortical changes followed from cortical changes in interconnected regions. These data highlight cellular location and interconnectivity as the major determinants of neuron survival, rather than phenotype.
authors.affiliation: Agriculture and Life Sciences Division, Lincoln University, Lincoln 7647, New Zealand.
authors.forename: Manfred J
authors.initials: MJ
authors.lastname: Oswald
authors.forename: David N
authors.initials: DN
authors.lastname: Palmer
authors.forename: Graham W
authors.initials: GW
authors.lastname: Kay
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Barwell
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002470:Cell Survival / Q000235:genetics; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D009434:Neural Pathways / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D009520:New Zealand; D010641:Phenotype; D034561:Sheep, Domestic; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: C447500:CLN6 protein, human; D008565:Membrane Proteins; D005680:gamma-Aminobutyric Acid