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CART treatment improves memory and synaptic structure in APP/PS1 mice.

Jia-li Jin¹, Anthony K F Liou², Yejie Shi²

¹1] Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China [2] The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.

Scientific Reports

|May 12, 2015

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Cocaine- and amphetamine-regulated transcript (CART) shows promise for Alzheimer's disease (AD) therapy. CART treatment improved memory and reduced oxidative stress in mice without affecting amyloid plaques.

Area of Science:

Neuroscience
Molecular Biology
Pathology

Background:

Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaques, synaptic loss, and cognitive decline.
Cocaine- and amphetamine-regulated transcript (CART) may protect against Aβ-induced toxicity.

Purpose of the Study:

To investigate CART localization in Alzheimer's model mice (APP/PS1).
To evaluate the therapeutic potential of exogenous CART administration in an AD mouse model.

Main Methods:

Immunohistochemical analysis of CART in APP/PS1 mice and human AD brain samples.
Behavioral testing (memory deficits) and electrophysiological recordings (long-term potentiation) in CART-treated APP/PS1 mice.
Mitochondrial function assays (membrane potential, complex activities, ATP levels) and oxidative stress marker analysis.

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Main Results:

Elevated CART immunoreactivity observed in the hippocampus and cortex of APP/PS1 mice, mirroring human AD cases.
Exogenous CART treatment ameliorated memory deficits and improved synaptic function without reducing Aβ plaque load.
CART administration preserved mitochondrial function, increased ATP production, reduced oxidative stress markers (ROS, 4-hydroxynonenal), and mitigated DNA damage.

Conclusions:

CART treatment demonstrates neuroprotective effects in an AD mouse model.
CART therapy may offer a novel therapeutic strategy for Alzheimer's disease by targeting mitochondrial dysfunction and oxidative stress.
Further research into CART's mechanisms and clinical efficacy is warranted.