Mitochondrial transfer from mesenchymal stem cells to neural stem cells protects against the neurotoxic effects of cisplatin.

Mesenchymal stem cells (MSCs) transfer healthy mitochondria to damaged acceptor cells via actin-based intercellular structures. In this study, we tested the hypothesis that MSCs transfer mitochondria to neural stem cells (NSCs) to protect NSCs against the neurotoxic effects of cisplatin treatment. Our results show that MSCs donate mitochondria to NSCs damaged in vitro by cisplatin.

Nasal administration of mesenchymal stem cells restores cisplatin-induced cognitive impairment and brain damage in mice.

Cognitive impairments are a common side effect of chemotherapy that often persists long after treatment completion. There are no FDA-approved interventions to treat these cognitive deficits also called 'chemobrain'. We hypothesized that nasal administration of mesenchymal stem cells (MSC) reverses chemobrain.

Switching from a high-fat cellulose diet to a high-fat pectin diet reverses certain obesity-related morbidities.

Background: Reducing caloric intake is a proven intervention for mitigating and modulating morbidities associated with overnutrition. Caloric restriction is difficult to affect clinically, therefore, dietary interventions that ameliorate the adverse consequences of overnutrition in the presence of a high-calorie diet would be of value.

Methods: Mice were fed an obesogenic diet containing 60% fat + 10% cellulose (HFC), or a control diet containing 10% fat + 10% cellulose (LFC) for 12 wks.

The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure.

Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue.

Pifithrin-μ Prevents Cisplatin-Induced Chemobrain by Preserving Neuronal Mitochondrial Function.

Cognitive impairment, termed chemobrain, is a common neurotoxicity associated with chemotherapy treatment, affecting an estimated 78% of patients. Prompted by the hypothesis that neuronal mitochondrial dysfunction underlies chemotherapy-induced cognitive impairment (CICI), we explored the efficacy of administering the small-molecule pifithrin (PFT)-μ, an inhibitor of mitochondrial p53 accumulation, in preventing CICI. Male C57BL/6J mice injected with cisplatin ± PFT-μ for two 5-day cycles were assessed for cognitive function using novel object/place recognition and alternation in a Y-maze.

Mechanisms of chemotherapy-induced behavioral toxicities.

While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life.

Modulation of neuroimmunity by adenosine and its receptors: metabolism to mental illness.

Adenosine is a pleiotropic bioactive with potent neuromodulatory properties. Due to its ability to easily cross the blood-brain barrier, it can act as a signaling molecule between the periphery and the brain. It functions through four (A1, A2A, A2B, and A3) cell surface G protein-coupled adenosine receptors (ARs) that are expressed in some combination on nearly all cells types within the CNS.

The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice.

Objectives: Excess fat in the diet can impact neuropsychiatric functions by negatively affecting cognition, mood and anxiety. We sought to show that the free fatty acid (FFA), palmitic acid, can cause adverse biobehaviors in mice that last beyond an acute elevation in plasma FFAs.

Methods: Mice were administered palmitic acid or vehicle as a single intraperitoneal (IP) injection.

Adenosine through the A2A adenosine receptor increases IL-1β in the brain contributing to anxiety.

Anxiety is one of the most commonly reported psychiatric conditions, but its pathogenesis is poorly understood. Ailments associated with activation of the innate immune system, however, are increasingly linked to anxiety disorders. In adult male mice, we found that adenosine doubled caspase-1 activity in brain by a pathway reliant on ATP-sensitive potassium (KATP) channels, protein kinase A (PKA) and the A2A adenosine receptor (AR).

Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice.

The prevalence of childhood obesity has risen dramatically and coincident with this upsurge is a growth in adverse childhood psychological conditions including impulsivity, depression, anxiety and attention deficit/hyperactive disorder (ADHD). Due to confounds that exist when determining causality of childhood behavioral perturbations, controversy remains as to whether overnutrition and/or childhood obesity is important. Therefore, we examined juvenile mice to determine if biobehaviors were impacted by a short-term feeding (1-3wks) of a high-fat diet (HFD).

Hypoxia/reoxygenation impairs memory formation via adenosine-dependent activation of caspase 1.

After hypoxia, a critical adverse outcome is the inability to create new memories. How anterograde amnesia develops or resolves remains elusive, but a link to brain-based IL-1 is suggested due to the vital role of IL-1 in both learning and brain injury. We examined memory formation in mice exposed to acute hypoxia.

Fasting induces an anti-inflammatory effect on the neuroimmune system which a high-fat diet prevents.

The neuroimmunological and behavioral consequences of a high-fat diet (HFD) are not well delineated. This is especially true when short term (24 h) fasting is used as a physiologic stressor. In this study, we examined the impact of a HFD on learning and memory and depressive-like behaviors to understand how fasting impacts neuroimmunity and whether obesity modulates the response.