Effects of cornel iridoid glycoside on CNS microenvironment related to neurogenesis in AD-like rat model induced by fimbria-fornix transaction

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive decline of cognitive abilities and by neuropathological features, including diffuse loss of neurons in the hippocampus and neocortex. The local microenvironment in regions of ongoing neurogenesis in the adult mammalian brain regulates the self-renewal, activation and differentiation of stem cells. Cornel iridoid glycoside (CIG) is a main component extracted from a traditional Chinese herb Cornus officinalis. Our previous study found that CIG promoted neurogenesis and angiogenesis in the brain and improved neurological function after focal cerebral ischemia in rats. The aim of the present study is to investigate the effects of CIG on CNS microenvironment related to neurogenesis in AD-like rat model. AD-like rat model was induced by fimbria-fornix transaction (FFT), which injures the cholinergic nerve fiber projection from basal forebrain to hippocampus and cerebral cortex. Neurobehavioral deficits were determined by Morris water maze and step-through tests. Pathological change was evaluated with Nissl's staining. The expression of neurotrophic factors, growth-associated protein (GAP-43), NogoA, chondroitin sulfate proteoglycan (CSPG), synaptophysin (SYP) and apoptosis-regulating factors was detected by western blot and immunohistochemistry. Intragastrical administration of CIG to FFT model rats for 28 days significantly improved the learning-memory ability; increased the number of neurons, elevated the expression of nerve growth factor (NGF) and its receptor TrkA, brain-derived neurotrophic factor (BDNF), GAP-43 and SYP; inhibited the expression of NogoA and CSPG which impede nerve growth; increased apoptosis-inhibiting factor Bcl-2 and decreased apoptosis-promoting factors Bax and cytochrome C in the hippocampus and cerebral cortex of model rats. CIG effectively increased the beneficial factors and decreased the harmful factors in CNS microenvironment related to neurogenesis in AD-like rat model induced by fimbria-fornix transaction, suggesting that CIG may help to promote neurogenesis and have the potential to treat AD and other neurodegenerative diseases. Key words: cornel iridoid glycoside; Cornus officinalis; Alzheimer's disease; CNS microenvironment; neurogenesis; fimbria-fornix transaction