ABSTRACT
Since mild thermal stress seems to exert neuroprotection via induction of heat-shock protein 70 kDa (hsp70), we tested whether hsp70 would preserve striatal bioelectrical activity under conditions of mitochondrial impairment. Corticostriatal slices from rats that had undergone mild thermal stress were exposed to either rotenone or 3-nitropropionic acid (3-NP), that selectively inhibits mitochondrial complex I and complex II, respectively. Rotenone is utilized to obtain an experimental model of Parkinson's disease while 3-NP replicates Huntington's disease phenotype in experimental animals. The cerebral hsp70 increase did not alter field potential amplitude of the slices but partially protected them against rotenone-induced neurotoxicity. Similarly, induction of hsp70 had also a partial neuroprotective effect on the neurotoxicity caused by 3-NP on striatal field potential. Since rotenone and 3-NP treatments mimic the mitochondrial impairment and oxidative stress that contribute to development of Parkinson's disease and Huntington's disease, these data suggest that induction of hsp70 might represent a possible neuroprotective mechanism against the pathophysiological chain of events implicated in these neurodegenerative disorders.
Subject(s)
Corpus Striatum/physiology , HSP70 Heat-Shock Proteins/biosynthesis , Heat-Shock Response , Mitochondria/physiology , Animals , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Electron Transport Complex I/antagonists & inhibitors , Electron Transport Complex II/antagonists & inhibitors , Huntington Disease/chemically induced , Huntington Disease/metabolism , Huntington Disease/physiopathology , In Vitro Techniques , Male , Mitochondria/drug effects , Neurons/physiology , Nitro Compounds , Parkinson Disease, Secondary/metabolism , Parkinson Disease, Secondary/physiopathology , Patch-Clamp Techniques , Propionates , Rats , Rats, Wistar , RotenoneABSTRACT
Measurement of total tau and amyloid beta1-42 (Ab42) in cerebrospinal fluid (CSF) improves diagnostic accuracy of Alzheimer's disease (AD). We examined a consecutive patient sample referred to our center for diagnostic assessment of cognitive decline. CSF tau and Abeta42 were assayed each week as routine neurochemical analyses. There were 119 patients investigated. These included 61 with probable AD (35 mild AD, 26 severe AD), 24 with mild cognitive impairment (MCI), 14 with vascular dementia, 11 with Lewy body dementia, and 9 with fronto-temporal dementia. Mild AD showed significantly lower CSF Abeta42 levels and significantly higher CSF tau levels than the other diagnostic groups; 79% of MCI patients had pathological values for both biomarkers. We confirm that these biomarkers have a role in the clinical work-up of patients with cognitive deficits.
