GW0742 NEWS - Cognitive Functions through Diabetes Management

Jul 18, 2020

GW0742 Studies

A growing body of evidence suggests that there is a relationship between age-related cognitive dysfunctions, such as Alzheimer’s disease (AD) and type II diabetes mellitus.

In the brain, insulin plays an important role in modulation of glucose transporter-4, which is crucial for regulating metabolism in neurons and energy production required for memory and other cognitive functions.
 
PAR-d activation might improve spatial memory and synaptic transmission in the hippocampus part of the brain.

An estimated 9% of the American population experiences type II diabetes mellitus (T2DM) due to diet or genetic predisposition.

Recent reports indicate that patients with T2DM are at increased risk for cognitive dysfunctions, as observed in conditions like Alzheimer’s disease (AD).

In addition, AD is the leading cause of dementia, highlighting the urgency of developing novel therapeutic targets for T2DM-induced cognitive deficits.

The peroxisome proliferator activated receptor-(PPAR-d) is highly expressed in the brain and has been shown to play an important role in spatial memory and hippocampal neurogenesis.

However, the effect of PPAR-d agonists on T2DM-induced cognitive impairment has not been explored. In this study, the effects of GW0742 (a selective PPAR-d agonist) on hippocampal synaptic transmission, plasticity, and spatial memory were investigated in the db/db mouse model of T2DM.

Oral administration of GW0742 for 2 weeks significantly improved hippocampal long-term potentiation. In addition, GW0742 effectively prevented deficits in hippocampal dependent spatial memory in db/db mice.

PPAR-d–mediated improvements in synaptic plasticity and behavior were accompanied by a significant recovery in hippocampal mediated synaptic
transmission.

Our findings suggest that activation of PPAR-d might ameliorate T2DM-induced
impairments in hippocampal synaptic plasticity and memory.

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