title: Chronic Lithium Treatment in a Rat Model of Basal Forebrain Cholinergic Depletion: Effects on Memory Impairment and Neurodegeneration.
abstract: Alzheimer's disease (AD) is an age-related neurodegenerative disorder with multifactorial etiopathogenesis, characterized by progressive loss of memory and other cognitive functions. A fundamental neuropathological feature of AD is the early and severe brain cholinergic neurodegeneration. Lithium is a monovalent cation classically utilized in the treatment of mood disorders, but recent evidence also advances a beneficial potentiality of this compound in neurodegeneration. Interestingly, lithium acts on several processes whose alterations characterize the brain cholinergic impairment at short and long term. On this basis, the aim of the present research was to evaluate the potential beneficial effects of a chronic lithium treatment in preventing the damage that a basal forebrain cholinergic neurodegeneration provokes, by investigating memory functions and neurodegeneration correlates. Adult male rats were lesioned by bilateral injections of the immunotoxin 192 IgG-Saporin into the basal forebrain. Starting 7 days before the surgery, the animals were exposed to a 30-day lithium treatment, consisting of a 0.24% Li2CO3 diet. Memory functions were investigated by the open field test with objects, the sociability and preference for social novelty test, and the Morris water maze. Hippocampal and neocortical choline acetyltransferase (ChAT) levels and caspase-3 activity were determined. Cholinergic depletion significantly impaired spatial and social recognition memory, decreased hippocampal and neocortical ChAT levels and increased caspase-3 activity. The chronic lithium treatment significantly rescued memory performances but did not modulate ChAT availability and caspase-3 activity. The present findings support the lithium protective effects against the cognitive impairment that characterizes the brain cholinergic depletion.
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Systemic Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gelfo
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Psychology, Sapienza University of Rome, Rome, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Cutuli
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Medicine, Medical School, Campus Bio-Medico University, Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Nobili
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of TECOS, Guglielmo Marconi University, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: De Bartolo
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Medicine, Medical School, Campus Bio-Medico University, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Amelio
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Psychology, Sapienza University of Rome, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Petrosini
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Systemic Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D053148:Caspase 3 / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000172:deficiency*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018020:Lithium Compounds / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology; D011897:Random Allocation; D017208:Rats, Wistar; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012919:Social Behavior
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018020:Lithium Compounds; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D054789:Ribosome Inactivating Proteins, Type 1; D002795:Choline O-Acetyltransferase; D000076985:Saporins; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: 192 IgG-Saporin; basal forebrain; cholinergic depletion; lithium; memory deficits; neuroprotection