Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide.
Pharmacological enhancement of hippocampal neurogenesis is a therapeutic approach for improvement of cognition in learning and memory disorders such as Alzheimer's disease. Here we report the development of an 11-mer peptide that we designed based on a biologically active region of the ciliary neurotrophic factor. This peptide, Peptide 6, induced proliferation and increased survival and maturation of neural progenitor cells into neurons in the dentate gyrus of normal adult C57BL6 mice. Furthermore, Peptide 6 increased the MAP2 and synaptophysin immunoreactivity in the dentate gyrus. Thirty-day treatment of the mice with a slow release bolus of the peptide implanted subcutaneously improved reference memory of the mice in Morris water maze. Peptide 6 has a plasma half life of over 6 h, is blood-brain barrier permeable, and acts by competitively inhibiting the leukemia inhibitory factor signaling. The fact that Peptide 6 is both neurogenic and neurotrophic and that this peptide is effective when given peripherally, demonstrates its potential for prevention and treatment of learning and memory disorders.
Chohan
Muhammad Omar
MO
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314-6399, USA.
Li
Bin
B
Blanchard
Julie
J
Tung
Yunn-Chyn
YC
Heaney
Agnes T
AT
Rabe
Ausma
A
Iqbal
Khalid
K
Grundke-Iqbal
Inge
I
D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000138:chemical synthesis* / Q000737:chemistry / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000138:chemical synthesis* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D020934:Ciliary Neurotrophic Factor; D010455:Peptides