title: Heat shock protein defenses in the neocortex and allocortex of the telencephalon.
abstract: The telencephalic allocortex develops protein inclusions before the neocortex in many age-related proteinopathies. One major defense mechanism against proteinopathic stress is the heat shock protein (Hsp) network. We therefore contrasted Hsp defenses in stressed primary neocortical and allocortical cells. Neocortical neurons were more resistant to the proteasome inhibitor MG132 than neurons from 3 allocortical subregions: entorhinal cortex, piriform cortex, and hippocampus. However, allocortical neurons exhibited higher MG132-induced increases in Hsp70 and heat shock cognate 70 (Hsc70). MG132-treated allocortical neurons also exhibited greater levels of protein ubiquitination. Inhibition of Hsp70/Hsc70 activity synergistically exacerbated MG132 toxicity in allocortical neurons more than neocortical neurons, suggesting that the allocortex is more reliant on these Hsp defenses. In contrast, astrocytes harvested from the neocortex or allocortex did not differ in their response to Hsp70/Hsc70 inhibition. Consistent with the idea that chaperones are maximally engaged in allocortical neurons, an increase in Hsp70/Hsc70 activity was protective only in neocortical neurons. Finally, the levels of select Hsps were altered in the neocortex and allocortex in vivo with aging.
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Posimo
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.
authors.forename: Justin N
authors.initials: JN
authors.lastname: Weilnau
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Gleixner
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Broeren
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Weiland
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Brodsky
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA. Electronic address: leakr@duq.edu.
authors.forename: Rehana K
authors.initials: RK
authors.lastname: Leak
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D005260:Female; D050883:HSC70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007976:Leupeptins / Q000633:toxicity; D018832:Molecular Chaperones; D019579:Neocortex / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D013687:Telencephalon; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D007976:Leupeptins; D018832:Molecular Chaperones; D061988:Proteasome Inhibitors; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Alzheimer's disease; Archicortex; Braak; Entorhinal cortex; Heme oxygenase-1; Hippocampus; Hsp70; Paleocortex; Parkinson's disease; Piriform cortex