An NCAM mimetic, FGL, alters hippocampal cellular morphometry in young adult (4 month-old) rats.
The neural cell adhesion molecule, NCAM, is ubiquitously expressed within the CNS and has roles in development, cognition, neural plasticity and regulation of the immune system. NCAM is thus potentially an important pharmacological target for treatment of brain diseases. A cell adhesion mimetic FGL, a 15 amino-acid peptide derived from the second fibronectin type-III module of NCAM, has been shown to act as a neuroprotective agent in experimental disease and ageing models, restoring hippocampal/cognitive function and markedly alleviating deleterious changes in the CNS. However, the effects of FGL on the hippocampus of young healthy rats are unknown. The present study has examined the cellular neurobiological consequences of subcutaneous injections of FGL, on hippocampal cell morphometry in young (4 month-old) rats. We determined the effects of FGL on hippocampal volume, pyramidal neuron number/density (using unbiased quantitative stereology), and examined aspects of neurogenesis (using 2D morphometric analyses). FGL treatment reduced total volume of the dorsal hippocampus (associated with a decrease in total pyramidal neuron numbers in CA1 and CA3), and elevated the number of doublecortin immunolabeled neurons in the dentate gyrus, indicating a likely influence on neurogenesis in young healthy rats. These data indicate that FGL has a specific age dependent effect on the hippocampus, differing according to the development and maturity of the CNS.
Department of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK.
Bunmi
B
Ojo
Paul L
PL
Gabbott
Payam
P
Rezaie
Nicola
N
Corbett
Nikolay I
NI
Medvedev
Thelma R
TR
Cowley
Marina A
MA
Lynch
Michael G
MG
Stewart
D000818:Animals; D018891:Dentate Gyrus / Q000737:chemistry / Q000187:drug effects; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D019006:Neural Cell Adhesion Molecules / Q000494:pharmacology*; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D009479:Neuropeptides / Q000032:analysis; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; C488618:NCAM protein (681-695), human; D019006:Neural Cell Adhesion Molecules; D009479:Neuropeptides; D018696:Neuroprotective Agents