Molar Loss Worsens Cognitive Decline in Rats Through a Signaling Pathway

Published on November 3, 2022

Imagine the brain as a bustling city. In this city, there are highways that help transport information and keep everything running smoothly. However, what happens when some of those highways start to deteriorate? Well, that’s what researchers wanted to find out with a study on molar loss and cognitive decline. They found that when rats experienced molar loss along with chronic cerebral ischemia, their cognitive function took a hit. The study looked at the activation of a specific signaling pathway called p38MAPK/NFκB-caspase 3 and its role in neuronal apoptosis (cell death) in the hippocampus. The results showed that molar loss further exacerbated the cognitive impairment in rats by upregulating the expression of genes involved in inflammation and cell death. This study sheds light on how something as seemingly innocent as molar loss can contribute to the development of cognitive decline. To learn more about this fascinating research and its implications, check out the full article!

BackgroundVascular dementia is characterized by reduced cognitive function due to chronic cerebral hypoperfusion and has become a significant public health challenge as the global population ages. Recent studies suggested that molar loss, a common problem among the elderly, may trigger the development of cognitive decline. Our previous study found that the molar loss affected cognitive dysfunction, and the astrocytes in the hippocampus of chronic cerebral ischemia rats were affected, but the underlying mechanism is unclear.MethodsIn this study, we established the animal model of molar loss with 2-VO rats and the Morris water maze was used to test the cognitive ability of rats in each group. The damage to neurons was observed via Nissl staining, and neuronal apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the hippocampus of the rats. Quantitative Real-Time PCR and immunohistochemistry and histology (IHC) were used to detect the expression of p38MAPK, NFκB, caspase 3, and iNOS in the hippocampus. The astrocytes were detected by IHC and Immunofluorescence analysis for GFAP. After 2-VO MO surgery, rats were administered DMSO or p38MAPK inhibitor (SB203580) by intrathecal injection.ResultsThe Morris water maze test showed that the molar loss aggravated spatial memory learning ability with chronic cerebral ischemia decreased in the rats. The neuronal damage and more apoptotic cells were observed in the hippocampus of 2-VO rats. After the molar loss, the mRNA and protein expression of iNOS, p38MAPK, NFκB, and caspase 3 were further upregulated in 2-VO rats. Molar loss upregulated GFAP expression, and the p38MAPK-positive cells were labeled with the astrocyte marker GFAP. SB203580 reduced cognitive impairment and apoptosis of hippocampal neurons in 2-VO rats following the molar loss.ConclusionMolar loss can aggravate cognitive impairment in 2-VO rats to a certain extent. The mechanism of molar loss exacerbating the cognitive decline in 2-VO rats may be associated with the activation of the p38MAPK-NFκB-caspase 3 signaling pathway, which induces neuronal apoptosis.

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