SLOH, a carbazole-based fluorophore, mitigates neuropathology and behavioral impairment in the triple-transgenic mouse model of Alzheimer's disease

Jan 9, 2018Neuropharmacology

SLOH, a fluorescent compound, reduces brain damage and behavior problems in a mouse model of Alzheimer's disease

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Abstract

One month of treatment with SLOH significantly improved memory impairments in 3xTg-AD mice.

SLOH treatment was associated with reduced levels of amyloid plaques in the brains of 3xTg-AD mice.
Cognitive function improvements were observed in both Morris Water Maze and Y-maze tasks after SLOH treatment.
The treatment also mitigated tau hyperphosphorylation and neuroinflammation in the mouse brain.
In vitro studies showed that SLOH reduced tau hyperphosphorylation and down-regulated GSK-3β activity in human neuroblastoma cells exposed to amyloid beta.

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Alzheimer's disease (AD) is a progressive neurodegenerative dysfunction characterized by memory impairment and brings a heavy burden to old people both in developing and developed countries. Amyloid hypothesis reveals that aggregation and deposition of amyloid plaques are the cause of AD neurodegeneration. SLOH, a carbazole-based fluorophore, is reported to inhibit amyloid beta (Aβ) aggregation in vitro. In the current study, we intended to evaluate the protective effect of SLOH in a triple transgenic AD mouse model (3xTg-AD). 3xTg-AD (10-month-old) were treated with SLOH (0.5, 1 and 2 mg kg) for one month via intraperitoneal injection. After treatment, cognitive function was assessed by Morris Water Maze (MWM) and Y-maze tasks. In addition, biochemical estimations were used to examine the degree of Aβ deposition, tau hyperphosphorylation and neuroinflammation in the brains of 3xTg-AD mice. An in vitro study was conducted on human neuroblastoma (SH-SY5Y) cells to determine the activity of SLOH on tau and GSK-3β using western blot and immunofluorescence staining. One month treatment with SLOH significantly ameliorated memory impairments in 3xTg-AD mice in MWM and Y-maze tests. Moreover, SLOH treatment mitigated the level of amyloid plaques, tau hyperphosphorylation and neuroinflammation in the mouse brain. SLOH also reduced tau hyperphosphorylation and down-regulated GSK-3β activity in Aβ induced neurotoxic SH-SY5Y cells. The promising results in mitigating amyloid plaques, tau hyperphosphorylation, neuroinflammation and ameliorating cognitive deficits following one-month treatment suggest that SLOH could be a potential multi-target molecule for the AD treatment. -1

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SLOH, a carbazole-based fluorophore, mitigates neuropathology and behavioral impairment in the triple-transgenic mouse model of Alzheimer's disease

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