All‐trans retinoic acid improved impaired proliferation of neural stem cells and suppressed microglial activation in the hippocampus in an Alzheimer's mouse model

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive impairment with neuronal loss. The number of patients suffering from AD has increased, but none of the present therapies stops the progressive symptoms in patients with AD. It has been reported that the activation of microglial cells induces harmful chronic inflammation, leading to neuronal death. Furthermore, the impairment of adult neurogenesis in the hippocampus has been observed earlier than amyloid plaque formation. Inflammatory response may lead to impaired adult neurogenesis in patients with AD. This study examines the relationship between adult neurogenesis and neuroinflammation using APPswe/PS1M146V/tauP301L (3 × Tg) mice. We observed a decline in the proliferation of neural stem cells and the occurrence of severe inflammation in the hippocampus of 3 × Tg mouse brains at 12 months of age. Previously, our research had shown an anti-inflammatory effect of all-trans retinoic acid (ATRA) in the 3 × Tg mouse brain. We found that ATRA has effects on the recovery of proliferative cells along with suppression of activated microglia in the hippocampus. These results suggest that the inhibition of microglial activation by ATRA leads to recovery of adult neurogenesis in the hippocampus in an AD mouse model. © 2016 Wiley Periodicals, Inc.

RETRACTED ARTICLE: Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation

“…A large number of studies have shown that inhibition of microglial cells activation improves the neurogenesis and cognitive performance [ 23 , 24 ]. In particular, inhibition of microglia activation by minocycline (a broad spectrum antibiotic, anti-inflammatory drug) has a profound neuroprotective effect associated with the improvement of spatial memory and neurogenesis during neuroinflammatory conditions [ 3 , 14 , 25 ].…”

Marginal Vitamin A Deficiency Exacerbates Memory Deficits Following A?1-42 Injection in Rats

“…However, the memory deficits induced by a full dose of Aβ 1-42 in the MVAD rats were apparent at 30 days but not 80 days post-injection. Previous studies have demonstrated that intracerebral fibrillar Aβ 1-42 induces proliferation and activation of microglia [37, 38] and RA suppresses microglial activation in an AD mouse model [39], so it is likely that MVAD accelerates the activation of microglia following Aβ 1-42 injection. A full dose of Aβ 1-42 might as well facilitate the damage of neurons.…”

Retinoic Acid Is Required for Oligodendrocyte Precursor Cell Production and Differentiation in the Postnatal Mouse Corpus Callosum

“…We also examined whether loss of RALDH2 expression affected microglial development. Microglial activation, including increased proliferation, can be mitigated by RA signaling (Dheen et al, 2005;Takamura et al, 2017), and changes in microglial function could impact OL development. By performing immunofluorescence staining for ionized calcium-binding adaptor molecule 1 (IBA1) at P7, 14, and P21, we found no significant differences between genotypes in terms of IBA1 ϩ cell number ( Fig.…”