abscisic-acid and Cognitive-Dysfunction

Alzheimer's disease (AD), a type of dementia, is the most common neurodegenerative disease in the elderly. Neuroinflammation caused by deposition of amyloid β (Aβ) is one of the most important pathological causes in AD. The isoprenoid phytohormone abscisic acid (ABA) has recently been found in mammals and was shown to be an endogenous hormone, acting in stress conditions. Although ABA has been associated with anti-inflammatory effects and reduced cognitive impairment in several studies, the mechanisms of ABA in AD has not been ascertained clearly. To investigate the clearance of Aβ and anti-inflammatory effects of ABA, we used quantitative real-time polymerase chain reaction and immunoassay. ABA treatment inhibited Aβ deposition and neuroinflammation, thus resulting in improvement of memory impairment in 5xFAD mice. Interestingly, these effects were not associated with activation of peroxisome proliferator-activated receptor gamma, well known as a molecular target of ABA, but related with modulation of the LanC-like protein 2 (LANCL2), known as a receptor of ABA. Taken together, our results indicate that ABA reduced Aβ deposition, neuroinflammation, and memory impairment, which is the most characteristic pathology of AD, via the upregulation of LANCL2. These data suggest that ABA might be a candidate for therapeutics for AD treatment.

Topics: Abscisic Acid; Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Cognitive Dysfunction; Disease Models, Animal; Female; Humans; Male; Membrane Proteins; Memory Disorders; Mice; Mice, Mutant Strains; Mice, Transgenic; Neurodegenerative Diseases; Phosphate-Binding Proteins; Plant Growth Regulators; PPAR gamma; Presenilin-1; Up-Regulation

Neuroinflammation and insulin resistance in the brain are intimately linked to neurodegenerative disorders, including Alzheimer's disease. Even though traditionally Alzheimer´s disease has been associated to Aβ deposits and hyperphosphorylated Tau intracellular tangles, several studies show that neuroinflammation may be the initial cause that triggers degeneration. Accordingly, a number of natural supplements that improves brain insulin sensitivity and reduce neuroinflammation have been proposed as good choices in the therapeutic prevention of cognitive decline. Further supporting this evidence, we show that phytohormone Abscisic Acid, can prevent memory impairment and neuroinflammation markers in a triple transgenic mouse model, where no peripheral inflammatory changes have occurred. Moreover, our data strongly suggests that early intervention is critical for good prognosis, and that cognitive improvement requires longer treatment than recovering neuroinflammation markers.

Topics: Abscisic Acid; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Brain; Cerebral Cortex; Cognitive Dysfunction; Disease Models, Animal; Hippocampus; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroimmunomodulation; Neuroprotective Agents; Plaque, Amyloid; tau Proteins