Selective disarrangement of the rostral telencephalic cholinergic system in heterozygous reeler mice.
Reelin (RELN) is a key molecule for the regulation of neuronal migration in the developing CNS. The reeler mice, which have spontaneous autosomal recessive mutation in the RELN gene, reveal multiple defects in brain development. Morphological, neurochemical and behavioral alterations have been detected in heterozygous reeler (HR) mice, suggesting that not only the presence, but also the level of RELN influences brain development. Several studies implicate an involvement of RELN in the pathophysiology of neuropsychiatric disorders in which an alteration of the cholinergic cortical pathways is implicated as well. Thus, we decided to investigate whether the basal forebrain (BF) cholinergic system is altered in HR mice by examining cholinergic markers at the level of both cell body and nerve terminals. In septal and rostral, but not caudal, basal forebrain region, HR mice exhibited a significant reduction in the number of choline acetyltransferase (ChAT) immunoreactive (ir) cell bodies compared with control mice. Instead, an increase in ChAT ir neurons was detected in lateral striatum. This suggests that an alteration in ChAT ir cell migration which leads to a redistribution of cholinergic neurons in subcortical forebrain regions occurs in HR mice. The reduction of ChAT ir neurons in the BF was paralleled by an alteration of cortical cholinergic nerve terminals. In particular, the HR mice presented a marked reduction of acetylcholinesterase (AChE) staining accompanied by a small reduction of cortical thickness in the rostral dorsomedial cortex, while the density of AChE staining was not altered in the lateral and ventral cortices. Present results show that the cholinergic basalo-cortical system is markedly, though selectively, impaired in HR mice. Rostral sub-regions of the BF and rostro-medial cortical areas show significant decreases of cholinergic neurons and innervation, respectively.
Sigala
S
S
Section of Pharmacology, Department of Biomedical Sciences and Biotechnology, University of Brescia Medical School, V.le Europa 11, 25123 Brescia, Italy.
Zoli
M
M
Palazzolo
F
F
Faccoli
S
S
Zanardi
A
A
Mercuri
N B
NB
Spano
P
P
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000002:abnormalities* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism*; D003342:Corpus Striatum / Q000002:abnormalities / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006579:Heterozygote; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009434:Neural Pathways / Q000002:abnormalities* / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013687:Telencephalon / Q000002:abnormalities* / Q000378:metabolism
D015415:Biomarkers; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D002795:Choline O-Acetyltransferase; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D000109:Acetylcholine