Early Life Stress, Depression And Parkinson’s Disease: A New Approach

Abstract This review aims to shed light on the relationship that involves exposure to early life stress, depression and Parkinson’s disease (PD). A systematic literature search was conducted in Pubmed, MEDLINE, EBSCOHost and Google Scholar and relevant data were submitted to a meta-analysis. Early life stress may contribute to the development of depression and patients with depression are at risk of developing PD later in life. Depression is a common non-motor symptom preceding motor symptoms in PD. Stimulation of regions contiguous to the substantia nigra as well as dopamine (DA) agonists have been shown to be able to attenuate depression. Therefore, since PD causes depletion of dopaminergic neurons in the substantia nigra, depression, rather than being just a simple mood disorder, may be part of the pathophysiological process that leads to PD. It is plausible that the mesocortical and mesolimbic dopaminergic pathways that mediate mood, emotion, and/or cognitive function may also play a key role in depression associated with PD. Here, we propose that a medication designed to address a deficiency in serotonin is more likely to influence motor symptoms of PD associated with depression. This review highlights the effects of an antidepressant, Fluvoxamine maleate, in an animal model that combines depressive-like symptoms and Parkinsonism

Long-Term Treatment with Fluvoxamine Decreases Nonmotor Symptoms and Dopamine Depletion in a Postnatal Stress Rat Model of Parkinson’s Disease

Nonmotor symptoms (NMS) such as anxiety, depression, and cognitive deficits are frequently observed in Parkinson’s disease (PD) and precede the onset of motor symptoms by years. We have recently explored the short-term effects of Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) on dopaminergic neurons in a parkinsonian rat model. Here, we report the long-term effects of Fluvoxamine, on early-life stress-induced changes in the brain and behavior. We specifically evaluated the effects of Fluvoxamine on brain mechanisms that contribute to NMS associated with PD in a unilateral 6-hydroxydopamine-lesioned rat model. A 14-day early postnatal maternal separation protocol was applied to model early-life stress followed by unilateral intracerebral infusion of 6-hydroxydopamine (6-OHDA) to model aspects of parkinsonism in rats. The anxiolytic, antidepressant, and cognitive effects of Fluvoxamine were confirmed using the elevated plus-maze (EPM) test, sucrose preference test (SPT), and Morris water maze (MWM) test. Further to that, our results showed that animals exposed to early-life stress displayed increased plasma corticosterone and malondialdehyde (MDA) levels which were attenuated by Fluvoxamine treatment. A 6-OHDA lesion effect was evidenced by impairment in the limb-use asymmetry test as well as decreased dopamine (DA) and serotonin levels in the striatum, prefrontal cortex, and hippocampus. These effects were surprisingly attenuated by Fluvoxamine treatment in all treated rats. This study is the first to suggest that early and long-term treatment of neuropsychological diseases with Fluvoxamine may decrease the vulnerability of dopaminergic neurons that degenerate in the course of PD

Dielectric Constant and Conductivity of Blood Plasma: Possible Novel Biomarkers for Alzheimer’s Disease

Alzheimer’s disease is a complex debilitating neurodegenerative disease for which there is no cure. The lack of reliable biomarkers for Alzheimer’s disease has made the evaluation of the efficacy of new treatments difficult and reliant on only clinical symptoms. In an aged population where cognitive function may be deteriorating for other reasons, the dependence on clinical symptoms is also unreliable. However, it is well established that infusion of β-amyloid into the dorsal hippocampus of rats leads to cognitive impairment in a rat model of Alzheimer’s disease. Moreover, the blood plasma of β-amyloid-lesioned rats exhibits a distinct variation of the dielectric constant and conductivity when compared to that of normal rats in a time-dependent manner. These two electric parameters of blood plasma may therefore act as potential biomarkers for dementia due to Alzheimer’s disease. This review is aimed at highlighting evidences that support blood plasma electrical properties, e.g., dielectric constant and conductivity as possible novel biomarkers for the early development and progression of dementia due to Alzheimer’s disease

Effect of long-term administration of antiretroviral drugs (Tenofovir and Nevirapine) on neuroinflammation and neuroplasticity in mouse hippocampi

The use of combination antiretroviral therapy (cART) has been successful in suppressing HIV-1 replication and restoring peripheral immune functioning in HIV-infected individuals. Despite these advances in the management of HIV, neurocognitive impairments continue to be diagnosed in HIV-infected patients on treatment, even when the viral load is low. Of interest is the observation that deficiencies in brain function in these individuals are marked by a persistent presence of neuroinflammation. Therefore, in this study we investigated whether long-term exposure to ART could contribute to neuroinflammation. Mice were subsequently administered a daily single dose of either Tenofovir disoproxil fumarate or Nevirapine orally for 8 weeks. After treatment, hippocampal tissue was collected from the brains of drug-treated and control mice and the levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and brain-derived neurotrophic factor (BDNF) determined. Our results showed that administration of Tenofovir disoproxil fumarate and Nevirapine induced astrogliosis and up-regulated IL-1β and TNF-α. In addition, we found that Nevirapine reduced the expression of BDNF. Together these results suggest that Nevirapine promotes inflammatory and reduces neuroprotective processes in the hippocampus of mice. Our findings therefore highlight the potential of ART to be harmful to the brain and as such these drugs may contribute to the development of HIV-associated neurocognitive disorder (HAND)

The effect of transdermally delivered OA (TD OA) alone and in combination with CHQ (CHQ-OA) on hepatic and gastrocnemius glycogen concentrations of <i>P</i>. <i>berghei</i>-infected rats in comparison with control animals (NIC and IC).

<p>The effect of transdermally delivered OA (TD OA) alone and in combination with CHQ (CHQ-OA) on hepatic and gastrocnemius glycogen concentrations of <i>P</i>. <i>berghei</i>-infected rats in comparison with control animals (NIC and IC).</p