ABSTRACT
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.
Subject(s)
Basal Nucleus of Meynert/abnormalities , Cell Adhesion Molecules, Neuronal/genetics , Cholinergic Fibers/metabolism , Extracellular Matrix Proteins/genetics , Nerve Tissue Proteins/genetics , Neural Pathways/abnormalities , Serine Endopeptidases/genetics , Telencephalon/abnormalities , Acetylcholine/metabolism , Animals , Basal Nucleus of Meynert/metabolism , Biomarkers/metabolism , Cell Differentiation/genetics , Cell Movement/genetics , Choline O-Acetyltransferase/metabolism , Corpus Striatum/abnormalities , Corpus Striatum/metabolism , Female , Gene Expression Regulation, Developmental/genetics , Heterozygote , Male , Mice , Mice, Neurologic Mutants , Neural Pathways/metabolism , Reelin Protein , Stem Cells/cytology , Stem Cells/metabolism , Telencephalon/metabolismSubject(s)
Community Networks/organization & administration , Computer Communication Networks/organization & administration , Regional Medical Programs/organization & administration , Community Networks/standards , Computer Communication Networks/standards , Demography , Eligibility Determination , Health Care Costs , Outcome Assessment, Health Care , Quality of Health Care , Regional Medical Programs/standards , United StatesABSTRACT
Many of the nation's employers now see direct contracting as a way to regain control over their costs for employees' healthcare benefits. As a result, provider competition for direct contracting arrangements with employers is likely to increase. For a healthcare system, the key to winning employers' contracts may lie in establishing system-wide pricing based on cost determinations. Once prices are set, a healthcare system should select the optimal revenue distribution method for maximizing returns and winning the cooperation of clinical staff.