title: Does age matter? Behavioral and neuro-anatomical effects of neonatal and adult basal forebrain cholinergic lesions.
abstract: The "cholinergic hypothesis" of dementia posits that the progressive loss of basal forebrain cholinergic neurons and the consequent decrease of acetylcholine levels in the deafferented projection sites are correlated with degree of cognitive decline in dementia. It has also been proposed that early dysfunction of the basal forebrain (BF) cholinergic system may be a risk factor for subsequent cognitive decline and possibly dementia. To characterize how age when BF cholinergic system is lesioned affects behavioral performances and morphology of neocortical neurons, seven-day-old rats were bilaterally i.c.v. injected with 192 IgG-saporin. In adulthood, these animals were subjected to spatial and associative tests. Subsequently, the morphology of parietal pyramidal neurons was assessed. The same behavioral and morphological evaluations were made in 80-day-old rats tested three weeks after bilateral i.c.v. injections of 192 IgG-saporin. The behavioral consequences of both cholinergic depletions were markedly similar. While both groups of lesioned animals exhibited very subtle deficits in the Morris water maze, they were significantly impaired in spatial discrimination in the open field and the radial maze. Paralleling behavioral data, the results of the morphological analysis revealed comparable increases in number and density of spines in apical and basal dendrites in layer-III parietal pyramidal neurons following both neonatal and adult cholinergic depletions. The present results demonstrate that the consequences of abnormal maturation of the cholinergic system are not substantially different from those evoked by cholinergic dysfunction in adulthood and provide a developmental psychobiological perspective of the neuronal foundations of the impaired cognitive functions.
authors.affiliation: IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: De Bartolo
authors.forename: Debora
authors.initials: D
authors.lastname: Cutuli
authors.forename: Laura
authors.initials: L
authors.lastname: Ricceri
authors.forename: Francesca
authors.initials: F
authors.lastname: Gelfo
authors.forename: Francesca
authors.initials: F
authors.lastname: Foti
authors.forename: Daniela
authors.initials: D
authors.lastname: Laricchiuta
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Scattoni
authors.forename: Gemma
authors.initials: G
authors.lastname: Calamandrei
authors.forename: Laura
authors.initials: L
authors.lastname: Petrosini
mesh_terms: D000109:Acetylcholine / Q000172:deficiency*; D000367:Age Factors; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000633:toxicity; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D001930:Brain Injuries / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D004193:Discrimination Learning / Q000187:drug effects; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D007859:Learning Disabilities / Q000209:etiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009460:Neurologic Examination; D009474:Neurons / Q000473:pathology*; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D054789:Ribosome Inactivating Proteins, Type 1 / Q000633:toxicity; D000076985:Saporins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D003911:Dextrans; D054789:Ribosome Inactivating Proteins, Type 1; C076397:biotinylated dextran amine; D005680:gamma-Aminobutyric Acid; D001710:Biotin; D002795:Choline O-Acetyltransferase; D000076985:Saporins; D000109:Acetylcholine