Intravenous infusion of nerve growth factor-secreting monocytes supports the survival of cholinergic neurons in the nucleus basalis of meynert in hypercholesterolemia brown-norway rats

• Published in: Journal of neuroscience research Vol. 92; no. 3; pp. 298 - 306
• Main Authors: Hohsfield, Lindsay A., Ehrlich, Daniela, Humpel, Christian
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2014; Wiley Subscription Services, Inc
• Subjects: Administration, Intravenous; Amyloid; Analysis of Variance; Animals; Basal Nucleus of Meynert - pathology; brain; Cell Movement - drug effects; Cell Movement - physiology; Choline O-Acetyltransferase - metabolism; Cholinergic Neurons - drug effects; Cytokines - metabolism; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; hypercholesterolemia; Hypercholesterolemia - pathology; Hypercholesterolemia - physiopathology; Hypercholesterolemia - therapy; Male; Maze Learning - drug effects; monocytes; Monocytes - metabolism; Myelin Sheath - metabolism; Myelin Sheath - ultrastructure; Nerve Growth Factor; Nerve Growth Factors - metabolism; Nerve Growth Factors - therapeutic use; NGF; Rats; monocytes; NGF; brain; hypercholesterolemia
• DOI: 10.1002/jnr.23309
• ISSN: 0360-4012

The recruitment of monocytes into the brain has been implicated in Alzheimer's disease and recent studies have indicated that monocytes can reduce amyloid plaque burden. Our previous investigations have shown that hypercholesterolemic rats develop cognitive, cholinergic, and blood–brain barrier dysfunction, but do not develop amyloid plaques. This study was designed to evaluate the effects of repeated intravenous (i.v.) infusion (via the dorsal penile vein) of primary monocytes on cognition, the cholinergic system, and cortical cytokine levels in hypercholesterolemia Brown‐Norway rats. In addition, we also transduced the monocytes with nerve growth factor (NGF) to evaluate whether these cells could be used to deliver a neuroprotective agent to the brain. Our results indicate that repeated i.v. infused monocytes migrate into the brains of hypercholesterolemic rats; however, this migration does not translate into marked effects on learning. Animals receiving NGF‐loaded monocytes demonstrate slightly improved learning and significantly elevated cholinergic neuron staining compared to treatment with monocytes alone. Furthermore, our data indicate that repeated infusion of monocytes does not lead to elevated cytokine secretion, indicating that no inflammatory response is induced. This study provides an experimental attempt to evaluate the effects of blood‐derived primary monocytes in hypercholesterolemia rats. © 2013 Wiley Periodicals, Inc.