Search

Multiple sclerosis (MS) is a chronic autoimmune disorder of central nervous system which is increasing worldwide. Although immunosuppressive agents are used for the treatment of MS disease, nevertheless the lack of non-toxic and efficient therapeutic method is perceptible. Hence, this study aims to evaluate the effect of Contactin-associated protein (Caspr) antibody-, poly ethylene glycol (PEG)- and exosome combined gold nanoparticles (GNPs) in comparison to Glatiramer acetate as a selective treatment of MS disease in the experimental autoimmune encephalomyelitis (EAE) mouse model. EAE was induced in female C57BL/6 mice and 25-day treatment with anti-Caspr-, PEG- and exosome combined GNPs was evaluated. Histopathological examination of spinal cord, regulatory T cells as well as inflammatory pathway including IFN-ɣ and IL-17 and mir-326 were investigated. The results showed the severity of MS symptoms was significantly decreased in all treated groups. Histological examination of the spinal cord indicated the reduced demyelination and immune cell infiltration. Besides, regulatory T cells were significantly increased following all treatments. Remarkably, the cytokine levels of IFN-ɣ and IL-17 as well as mir-326 is altered in treated groups. Taken together, the obtained findings demonstrate that the administration of anti-Caspr-, PEG- and exosome combined GNPs can be considered a potential treatment in MS disease. [ABSTRACT FROM AUTHOR]

Early life alteration in the activity of gamma-aminobutyric acid (GABA) receptors is associated with long-lasting developmental effects on the brain and behavior. GABAA receptors act as excitatory rather than inhibitory in neonates. Excessive activation of GABAA receptors during the early postnatal period may affect cognitive functions later in life. In this study, we sought to determine whether neonatal activation of GABAA receptors with muscimol can alter the electrophysiology profile of hippocampal CA1 neurons and spatial learning and memory in adult rats. Male and female Wistar rat pups received a subcutaneous injection of either saline or muscimol (500 µg/kg) on postnatal days (PND) 7, 9, and 11 and then underwent different electrophysiology and behavioral experiments in adulthood. Early life treatment with muscimol did not alter the basic synaptic transmission but significantly reduced the paired-pulse facilitation (PPF) in the CA1 area. Neonatal application of muscimol led to a pronounced decrease in long-term potentiation (LTP) and long-term depression (LTD) in CA1 neurons along with a declined theta-burst responses in both sexes. We obtained some evidence that neonatal GABAA activation leads to reduced brain-derived neurotrophic factor (BDNF) in the hippocampus and prefrontal cortex. Our electrophysiology data was supported with spatial reference and working memory deficits in rats. This study provides the first detailed description of altered electrophysiology in hippocampal CA1 neurons in adult rats undergone GABAA activation early in life. [ABSTRACT FROM AUTHOR]

The gut-microbiota–brain axis plays an important role in stress-related disorders, and dysfunction of this complex bidirectional system is associated with Alzheimer's disease. This study aimed to assess the idea that whether gut microbiota depletion from early adolescence can alter anxiety- and depression-related behaviours in adult mice with or without Alzheimer-like disease. Male C57BL/6 mice were treated with an antibiotic cocktail from weaning to adulthood. Adult mice received an intracerebroventricular injection of amyloid-beta (Aβ)1–42, and were subjected to anxiety and depression tests. We measured, brain malondialdehyde and glutathione following anxiety tests, and assessed brain oxytocin and the hypothalamic–pituitary–adrenal (HPA) axis function by measuring adrenocorticotrophic hormone (ACTH) and corticosterone following depression tests. Healthy antibiotic-treated mice displayed significant decreases in anxiety-like behaviours, whereas they did not show any alterations in depression-like behaviours and HPA axis function. Antibiotic treatment from early adolescence prevented the development of anxiety- and depression-related behaviours, oxidative stress and HPA axis dysregulation in Alzheimer-induced mice. Antibiotic treatment increased oxytocin in the brain of healthy but not Alzheimer-induced mice. Taken together, these findings suggest that gut microbiota depletion following antibiotic treatment from early adolescence might profoundly affect anxiety- and depression-related behaviours, and HPA axis function in adult mice with Alzheimer-like disease. [ABSTRACT FROM AUTHOR]

Gestational stress can increase postpartum depression in women. To treat maternal depression, fluoxetine (FLX) is most commonly prescribed. While FLX may be effective for the mother, at high doses it may have adverse effects on the fetus. As environmental enrichment (EE) can reduce maternal stress effects, we hypothesized that a subthreshold dose of FLX increases the impact of EE to reduce anxiety and depression-like behavior in postpartum dams exposed to gestational stress. We evaluated this hypothesis in mice and to assess underlying mechanisms we additionally measured hypothalamic–pituitary–adrenal (HPA) axis function and brain levels of the hormone oxytocin, which are thought to be implicated in postpartum depression. Gestational stress increased anxiety- and depression-like behavior in postpartum dams. This was accompanied by an increase in HPA axis function and a decrease in whole-brain oxytocin levels in dams. A combination of FLX and EE remediated the behavioral, HPA axis and oxytocin changes induced by gestational stress. Central administration of an oxytocin receptor antagonist prevented the remediating effect of FLX + EE, indicating that brain oxytocin contributes to the effect of FLX + EE. These findings suggest that oxytocin is causally involved in FLX + EE mediated remediation of postpartum stress-related behaviors, and HPA axis function in postpartum dams. [ABSTRACT FROM AUTHOR]

Rationale: Considerable clinical and experimental studies have shown that depression-related disorders are the most common neuropsychiatric symptoms in Alzheimer's disease (AD), affecting as many as 20–40% of patients. An increasing amount of evidence shows that monoamine-based antidepressant treatments are not completely effective for depression treatment in patients with dementia. Minocycline, a second-generation tetracycline antibiotic, has been gaining research and clinical attention for the treatment of different neuropsychiatric disorders, and more recently depression symptom in humans. Methods: In the present study, we investigated the effects of Aβ1–42 administration alone or in combination with minocycline treatment on depression-like behaviors and anti/pro-inflammatory cytokines such as interleukin(IL)-10, IL-β, and tumor necrosis factor (TNF)-α in the hippocampus of rats. Results: Our results showed that Aβ1–42 administration increased depression-related behaviors in sucrose preference test, tail suspension test, novelty-suppressed feeding test, and forced swim test. We also found significant increases in IL-1β and TNF-α levels in the hippocampus of Aβ1–42-treated rats. Interestingly, minocycline treatment significantly reversed depression-related behaviors and the levels of hippocampal cytokines in Aβ1–42-treated rats. Conclusion: These findings support the idea that there is a significant relationship among AD, depression-related symptoms, and pro-inflammatory cytokines in the brain, and suggest that antidepressant-like impacts of minocycline could be due to its anti-inflammatory properties. This drug could be of potential interest for the treatment of depression in patients with Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Traumatic brain injury is a complex phenomenon leading to neurological diseases and persistent disability that currently affects millions of people worldwide. Increasing evidence shows that a wide range of patients with mild traumatic brain injury (mTBI) suffer from depression during the initial stages of injury and the post-acute stages of recovery. However, the underlying mechanisms involved in depression following mTBI are still not fully understood. The aim of this study was to determine whether serotonin 5-hydroxytryptamine-1A (5-HT1A) receptor is involved in the regulation of depression-related behaviors following mild traumatic brain injury in mice. Mice with or without mTBI received intracerebroventricular injections of 5-HT1A receptor agonist (8-OH-DPAT) or antagonist (WAY-100635) for 5 days, then animals were subjected to behavioral tests. Four behavioral tests including novelty-suppressed feeding test, forced swim test, sucrose preference test and tail suspension test were used to evaluate depression-related symptoms in animals. Our results indicated that mTBI induction increased depression-like symptoms through altering serotonin 5-HT1A receptor activity in the brain. Activation of 5-HT1A receptor by a subthreshold dose of 8-OH-DPAT led to a significant decrease in depression-like behaviors, whereas blockade of 5-HT1A receptor by a subthreshold dose of WAY-100635 resulted in a considerable increase in depression-like phenotypes in mTBI-induced mice. The major strength of the present study is that depression-related symptoms were assessed in four behavioral tests. The present study supports the idea that disturbances in the function of serotonergic system in the brain following mTBI can play an important role in the regulation of depression-related behaviors. [ABSTRACT FROM AUTHOR]

Early life overfeeding is associated with cognitive decline and anxiety-like behaviors in later life. It is not clear whether there are individual differences in the effects of early life overfeeding and what the underlying mechanistic pathways are. We investigated the long-lasting effects of small litter size, an experimental manipulation to induce neonatal overfeeding, in two strains of mice, C57BL/6 and NMRI. We measured body weight, learning and memory, anxiety-related behaviors, interleukin-(IL)-1β and brain-derived-neurotrophic-factor (BDNF) levels in the hippocampus, and both basal and stress corticosterone levels in adult mice which have been nursed in small litters compared with those from control litters. Our findings showed that small litter size led to increased body weight in both strains of mice. Small litter size significantly decreased spatial memory and hippocampal BDNF levels, and increased hippocampal IL-1β, in NMRI mice, but not C57BL/6 mice. Interestingly, we found that small litter size resulted in a significant increase in anxiety-like behaviors and stress-induced corticosterone in NMRI mice, whereas small litter size reduced anxiety-like symptoms and stress-induced corticosterone levels in C57BL/6 mice. These data show that small litter size, which is life-long associated with increased body weight, affects memory and anxiety-related behaviors in a strain-dependent manner in male mice. This suggests that there are individual differences in the developmental consequences of early life overfeeding. [ABSTRACT FROM AUTHOR]