title: Regional comparison of the neurogenic effects of CNTF-derived peptides and cerebrolysin in AβPP transgenic mice.
abstract: Adult neurogenesis, the production of new neurons in certain brain regions, is known to decrease with age and the loss of neurogenic potential has been implicated in Alzheimer's disease (AD), a leading cause of dementia in the elderly. Cerebrolysin (CBL) has been shown to increase neurogenesis in models of stroke and AD. CBL is composed of small peptides with activity similar to neurotrophic factors including ciliary neurotrophic factor (CNTF), which may mediate its neurogenic effects. This study compares the effects of CBL and two peptides with corresponding to an active region of CNTF (Peptide 6 and 6A) across neurogenic brain regions in amyloid-β protein precursor (AβPP) transgenic (tg) mice. Both CBL and Peptides 6 and 6A were able to increase the numbers of neuroblasts (DCX+ cells) and BrdU+ cells in a regionally specific manner across the subventricular zone, olfactory bulb, and hippocampus. The increased generation of new cells and cell survival in animals treated with Peptides 6 and 6A was accompanied by an increase in PCNA+ cells. In contrast, AβPP tg mice treated with CBL displayed reduced levels of TUNEL staining, while levels of PCNA were unaltered. Collectively these results demonstrate that while CBL and Peptides 6 and 6A all potentiate neurogenesis in the AβPP tg mice, their relative modes of action may differ with CBL associated with reduced apoptosis and Peptides 6 and 6A working by augmenting cell proliferation. These results are consistent with a potential therapeutic relevance for Peptides 6 and 6A in AD and other disorders characterized by neurogenic deficits.
authors.affiliation: University of California, San Diego, Neurosciences Department, La Jolla, CA 92093-0624, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.forename: Kiren
authors.initials: K
authors.lastname: Ubhi
authors.forename: Edith
authors.initials: E
authors.lastname: Doppler
authors.forename: Philipp
authors.initials: P
authors.lastname: Novak
authors.forename: Herbert
authors.initials: H
authors.lastname: Moessler
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Julie
authors.initials: J
authors.lastname: Blanchard
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.forename: Leslie
authors.initials: L
authors.lastname: Crews
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D000596:Amino Acids / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D020934:Ciliary Neurotrophic Factor; C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; C075222:amyloid beta-protein (1-42); C006952:cerebrolysin; D001973:Bromodeoxyuridine