Bornyl Acetate and Menthol Provide Neuroprotection Against Lipopolysaccharide-Induced Alzheimer’s Disease-Like Condition in C57BL/6 Mice by Downregulating NARC-1 Lipid Antagonist

Article

作者: Kumaresan, Manikandan ; Ravi, Sangeetha ; Raman, Thiagarajan ; Martin, Livya Catherene ; Krishnan, Mahalakshmi ; Manikandan, Beulaja ; Ramar, Manikandan

Alzheimer's disease (AD) is a progressive neurological illness that causes Aβ deposition and cognitive impairments. Anti-cholinesterase and anti-depressant drugs are used as medications; however, their side effects spotlight the need for alternate treatments. Bornyl acetate and menthol are monoterpenes with bioactive potential investigated against inflammation induced by lipopolysaccharide (LPS) in C57BL/6 mice. In our study, we analysed various behavioural changes along with memory activities as well as assessed neuronal damage, acetylcholinesterase activity, amyloid deposition, mitochondrial membrane integrity, calcium deposition and oxidation derivatives. In addition, we also examined gene and protein expression associated with lipid dysfunction in neuroinflammation. Our findings revealed that monoterpenes such as bornyl acetate and menthol potentially improved LPS-induced behaviour changes and cognitive activities. In addition, these compounds have the potential effects against amyloid plaque formation, calcium build-up, mitochondrial membrane damage and oxidative markers (malondialdehyde, protein carbonyls and advanced glycation end products) in the LPS-injected C57BL/6 mice. Treatment with bornyl acetate and menthol also inhibited neural apoptosis-regulated convertase (NARC-1)/proprotein convertase subtilisin/kexin type 9 (PCSK-9) by upregulating low-density lipoprotein receptor-related protein (LRP)-1 protein expression. Cholesterol oxidation genes, including 11β-hydroxysteroid dehydrogenase 1 & 2, as well as proinflammatory microglial, apoptotic and amyloidogenic protein and gene expression, were decreased respectively when treated with monoterpenes while promoting the upregulation of anti-inflammatory. Based on the results, we concluded that these compounds can potentially target and prevent neuroinflammation, including Alzheimer's disease.

2025-12-01·Brain, behavior, & immunity - health

Immune and metabolic disturbance as a function of genetic risk and phase of illness in major depression

Article

作者: Howard, David M ; Kämpe, Robin ; Gilchrist, Lachlan ; Proitsi, Petroula ; Hamilton, J Paul ; Östman, Lars ; Paul, Elisabeth R ; Heilig, Markus

Immune and metabolic factors are important in the pathophysiology of major depressive disorder (MDD) but we know little about how these factors manifest in relation to the status of depressive illness-from genetic risk for MDD, to a depressive episode, to depression in remission. Using genetic, diagnostic, biometric, and blood-bioassay data from the UK Biobank, we examined measures of pro-inflammatory signaling (C-reactive protein) and metabolic dysfunction (metabolic syndrome symptomatology) in females (N = 37,806) and males (N = 17,946) as a function of polygenic load for MDD (high versus low) interacting with depression status (never depressed, currently depressed, or depression in remission). We examined socioeconomic status (SES) as an exploratory factor in this design. Groups were matched for several confounders using a propensity-matching algorithm (females: n = 6301 per group for N = 37,806; n = 2991 per group for N = 17,946). In females we found increased inflammation and metabolic dysfunction in the higher-versus-lower PRS quartile, in those below-versus-above the median SES, and in those suffering currently from depression relative to their remitted depressed and healthy counterparts. This association remained when considering only non-psychotropic-medicated persons. Nonetheless, we also saw in both male and female samples that measures of immunological and metabolic dysfunction increased with increasing anti-depressant medication load. We discuss these findings in terms of the epidemiological significance of immune and metabolic functioning in depression and their paradoxical relation with antidepressant treatment.

2024-09-01·PREVENTIVE MEDICINE

The cross-sectional association between dietary total, animal, and plant-based protein intake and the prevalence and severity of depressive symptoms in Dutch adults with type 2 diabetes: The Hoorn Diabetes Care System cohort

Article

作者: den Braver, Nicolette R ; Rutters, Femke ; Groeneveld, Lenka ; Beulens, Joline W ; Kremers, Sanne H M ; Migchelbrink, Maaike M ; Blom, Marieke T ; Elders, Petra J M

OBJECTIVE:

This study aimed to investigate cross-sectional associations of total, animal, and plant-based protein intake and depressive symptoms in Dutch adults with type 2 diabetes (T2D).

METHODS:

We included 1137 individuals with T2D (aged 68.6 ± 9.0) from the Hoorn Diabetes Care System cohort. Energy-adjusted protein intake was assessed using a validated Food Frequency Questionnaire. The nine-item Patient Health Questionnaire (PHQ-9) was used to assess the prevalence of depressive symptoms (PHQ-9 ≥ 10 and/or anti-depressant use) and the severity of depressive symptoms (continuous PHQ-9 score). Associations between total, animal, and plant-based protein (quartiles) with depressive symptoms were assessed using multiple logistic and linear regression.

RESULTS:

Highest intake of total, animal, and plant-based protein was not associated with the prevalence of depressive symptoms, compared to lowest intake (e.g., total protein, ORQ4vsQ1:0.75, 95%CI 0.42;1.32). For the severity of depressive symptoms, highest total protein intake was significantly associated with lower PHQ-9 scores (ORQ4vsQ1:0.87, 95%CI 0.75;1.00), compared to lowest intake. Animal protein was not associated with the severity of depressive symptoms (β ∼ 1), while the association for plant-based protein was marginally non-significant (βQ4vsQ1:0.88, 95%CI 0.76;1.02).

CONCLUSION:

In individuals with T2D, higher total protein intake was associated with reduced severity of depressive symptoms, but not with the prevalence of depressive symptoms. Further prospective research with a larger sample size is needed to confirm these associations.

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