Pitavastatin attenuates hypercholesterolemia-induced decline in serotonin transporter availability

Area of Science:

• Neuroscience and Pharmacology
• Cardiovascular Research
• Metabolic Disorders

Background:

• Hypercholesterolemia is linked to increased inflammation and impaired serotonin neurotransmission, potentially contributing to depressive symptoms.
• The specific effects of statins, like pitavastatin, on serotonin transporter (SERT) function in hypercholesterolemia are not well understood.
• This study investigates pitavastatin's potential to counteract the neurobiological impacts of hypercholesterolemia.

Purpose of the Study:

• To evaluate the neurobiological effects of pitavastatin in a mouse model of hypercholesterolemia.
• To determine if pitavastatin can modulate serotonin transporter (SERT) availability in the context of high cholesterol and inflammation.
• To assess pitavastatin's impact on lipid profiles, inflammatory markers, and depressive-like behaviors.

Main Methods:

• Utilized low-density lipoprotein receptor knockout (LDLR-/-) mice fed either a standard diet, a high-fat diet (HFD), or an HFD supplemented with pitavastatin.
• Assessed lipid profiles and inflammatory markers (IL-1α, MCP-1/CCL2, TNF-α) over 20 weeks.
• Employed small-animal positron emission tomography (PET) with 4-[18F]-ADAM to measure serotonin transporter (SERT) availability in brain regions.

Main Results:

• Pitavastatin significantly reduced total and LDL cholesterol in HFD-fed mice.
• Elevated inflammatory markers were decreased by pitavastatin treatment.
• PET imaging revealed reduced SERT availability in HFD mice, which was improved by pitavastatin, particularly in mood-related brain areas. Sucrose preference showed a trend towards improvement, suggesting reduced depressive-like behavior.

Conclusions:

• Pitavastatin demonstrates multifaceted benefits, lowering cholesterol and reducing inflammation.
• The drug enhances serotonin transporter (SERT) availability, indicating a potential therapeutic role in mood regulation.
• These findings suggest pitavastatin may help alleviate depressive symptoms associated with hypercholesterolemia.