Lead-induced effects on learning/memory and fear/anxiety are correlated with disturbances in specific cholinesterase isoform activity and redox imbalance in adult brain.
The aim of the present study was to investigate whether the underlying mechanism of lead (Pb)-induced effects on learning/memory and fear/anxiety behavior involves changes either on AChE G4 (most abundant in brain) or on G1 isoform activity, and/or to a putative local disruption of oxidant/antioxidant balance. Adult male mice were randomly divided into two groups (18 animals/group): a vehicle group [500ppm (mg/L) CH3COONa/day for 4weeks in their drinking water] and a Pb-treated group [500ppm Pb(CH3COO)2/day for 4weeks in their drinking water]. At the end of the treatment period, mice were subjected to the behavioral tasks. Learning/memory was tested by step-through passive avoidance test, whereas fear/anxiety was studied using the elevated plus-maze and thigmotaxis tests. Pb levels in mice brain were determined using atomic absorption spectrometry. AChE activity was determined colorimetrically, and GSH and MDA levels fluorometrically in whole brain minus cerebellum, cerebral cortex, midbrain, hippocampus, striatum and cerebellum. The possible correlations between learning/memory or fear/anxiety behavior with the AChE activity and/or the lipid peroxidation levels and GSH content were also examined. Pb consumption caused significant deficits on mice learning/memory ability and increased anxiety. The consumption of the Pb solution inhibited the activity of the two AChE isoforms in all brain regions tested. Moreover, Pb exposure increased lipid peroxidation and decreased GSH levels in all brain regions examined. Spearman correlation analysis revealed that the coefficients between the particular behaviors, AChE activity and redox balance were brain region- and AChE isoform-specific.
Laboratory of Human & Animal Physiology, Department of Biology, University of Patras, 26500 Patras, Greece.
Anastasia-Varvara
AV
Ferlemi
Laboratory of Human & Animal Physiology, Department of Biology, University of Patras, 26500 Patras, Greece.
Dionisis
D
Avgoustatos
Laboratory of Human & Animal Physiology, Department of Biology, University of Patras, 26500 Patras, Greece.
Alexandros G
AG
Kokkosis
Lavrion Technology and Cultural Park, 1 Athinon-Lavriou Avenue, 19500 Lavrion, Greece.
Vasilis
V
Protonotarios
NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA 02114, USA. Electronic address: cconst12@yahoo.com.
Caterina
C
Constantinou
Laboratory of Human & Animal Physiology, Department of Biology, University of Patras, 26500 Patras, Greece. Electronic address: margar@upatras.gr.
Marigoula
M
Margarity
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001008:Anxiety Disorders / Q000209:etiology / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D005239:Fear / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D020265:Lead Poisoning, Nervous System, Adult / Q000150:complications / Q000503:physiopathology*; D007858:Learning / Q000502:physiology; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D008807:Mice, Inbred BALB C; D009483:Neuropsychological Tests
D007527:Isoenzymes; D008315:Malondialdehyde; D000110:Acetylcholinesterase; D005978:Glutathione
Acetylcholinesterase; Anxiety-like behavior; Correlation analysis; Lead; Learning/memory; Redox balance