TY - JOUR
T1 - Does age matter? behavioral and neuro - Anatomical effects of neonatal and adult basal forebrain cholinergic lesions
AU - De Bartolo, Paola
AU - Cutuli, Debora
AU - Ricceri, Laura
AU - Gelfo, Francesca
AU - Foti, Francesca
AU - Laricchiuta, Daniela
AU - Scattoni, Maria Luisa
AU - Calamandrei, Gemma
AU - Petrosini, Laura
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - 192 IgG-saporin
KW - Age effect
KW - Alzheimer's disease
KW - cholinergic lesion
KW - neuronal morphology
KW - pyramidal neurons
KW - rat
KW - spatial function
UR - http://www.scopus.com/inward/record.url?scp=77954494783&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954494783&partnerID=8YFLogxK
U2 - 10.3233/JAD-2010-1355
DO - 10.3233/JAD-2010-1355
M3 - Article
C2 - 20164586
AN - SCOPUS:77954494783
VL - 20
SP - 207
EP - 227
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 1
ER -