Zinc Supplementation During Pregnancy Alleviates Lipopolysaccharide-Induced Glial Activation and Inflammatory Markers Expression in a Rat Model of Maternal Immune Activation.

Maternal immune activation (MIA) model has been profoundly described as a suitable approach to study the pathophysiological mechanisms of neuropsychiatric disorders, including schizophrenia. Our previous study revealed that prenatal exposure to lipopolysaccharide (LPS) induced working memory impairments in only male offspring. Based on the putative role of prefrontal cortex (PFC) in working memory process, the current study was conducted to examine the long-lasting effect of LPS-induced MIA on several neuroinflammatory mediators in the PFC of adult male pups.

Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model.

Maternal infection during pregnancy is considered a key risk factor for developing schizophrenia in offspring. There is evidence that maternal exposure to infectious agents is associated with fetal zinc deficiency. Due to the essential role of zinc in brain function and development, in the present study, we activated maternal immune system using lipopolysaccharide (LPS) as a model of schizophrenia to examine whether zinc supplementation throughout pregnancy can reverse LPS-induced deleterious effects.

Mechanisms of Below-Level Pain Following Spinal Cord Injury (SCI).

Mechanisms of below-level pain are discoverable as neural adaptations rostral to spinal injury. Accordingly, the strategy of investigations summarized here has been to characterize behavioral and neural responses to below-level stimulation over time following selective lesions of spinal gray and/or white matter. Assessments of human pain and the pain sensitivity of humans and laboratory animals following spinal injury have revealed common disruptions of pain processing.

A Review of Cognitive Outcomes Across Movement Disorder Patients Undergoing Deep Brain Stimulation.

Although the benefit in motor symptoms for well-selected patients with deep brain stimulation (DBS) has been established, cognitive declines associated with DBS can produce suboptimal clinical responses. Small decrements in cognition can lead to profound effects on quality of life. The growth of indications, the expansion of surgical targets, the increasing complexity of devices, and recent changes in stimulation paradigms have all collectively drawn attention to the need for re-evaluation of DBS related cognitive outcomes.

Loss of IBA1-Expression in brains from individuals with obesity and hepatic dysfunction.

Microglia, the brain's resident immune cells, exhibit constitutive expression of the ionized calcium binding adaptor molecule 1 (IBA1), a cytoplasmic protein with actin and calcium-binding functions involved in membrane ruffling. Microglia are long-lived cells that exhibit a senescent morphology (dystrophy) with aging, which may be indicative of cell dysfunction. It has been reported that dystrophy of IBA1-positive microglia is exacerbated in obese humans.

Methamphetamine neurotoxicity, microglia, and neuroinflammation.

Methamphetamine (METH) is an illicit psychostimulant that is subject to abuse worldwide. While the modulatory effects of METH on dopamine neurotransmission and its neurotoxicity in the central nervous system are well studied, METH's effects on modulating microglial neuroimmune functions and on eliciting neuroinflammation to affect dopaminergic neurotoxicity has attracted considerable attention in recent years. The current review illuminates METH-induced neurotoxicity from a neuropathological perspective by summarizing studies reporting microglial activation after METH administration in rodents.

Modulatory role of the intra-accumbal CB1 receptor in protein level of the c-fos and pCREB/CREB ratio in the nucleus accumbens and ventral tegmental area in extinction and morphine seeking in the rats.

Brain reward and motivation circuit begin from the ventral tegmental area (VTA) that its dopaminergic terminals project to various regions of the brain including the nucleus accumbens (NAc). This reward circuit is influenced by drugs of abuse such as morphine and cannabinoid. The present study tried to investigate the role of the intra-accumbal CB1 receptor in the c-fos level and pCREB/CREB ratio in the NAc and the VTA during reinstatement phase of morphine-induced conditioned place preference (CPP) by western blotting.

HIV-1 Tat regulation of dopamine transmission and microglial reactivity is brain region specific.

The transactivator of transcription protein, HIV-1 Tat, is linked to neuroAIDS, where degeneration of dopamine neurons occurs. Using a mouse model expressing GFAP-driven Tat protein under doxycycline (Dox) regulation, we investigated microglial-neuronal interactions in the rostral substantia nigra pars compacta (SNc). Immunohistochemistry for microglia and tyrosine hydroxylase (TH) showed that the ratio of microglia to dopamine neurons is smaller in the SNc than in the ventral tegmental area (VTA) and that this difference is maintained following 7-day Dox exposure in wild type animals.

Longitudinal Follow-up of Impedance Drift in Deep Brain Stimulation Cases.

Background: Impedance is an integral property of neuromodulation devices that determines the current delivered to brain tissue. Long-term variability in therapeutic impedance following deep brain stimulation (DBS) has not been extensively investigated across different brain targets. The aim was to evaluate DBS impedance drift and variability over an extended postoperative period across common DBS targets.

Thalamic DBS with a constant-current device in essential tremor: A controlled clinical trial.

Introduction: This study of thalamic deep brain stimulation (DBS) investigated whether a novel constant-current device improves tremor and activities of daily living (ADL) in patients with essential tremor (ET).

Methods: A prospective, controlled, multicenter study was conducted at 12 academic centers. We investigated the safety and efficacy of unilateral and bilateral constant-current DBS of the ventralis intermedius (VIM) nucleus of the thalamus in patients with essential tremor whose tremor was inadequately controlled by medications.

Degenerative Ataxias: challenges in clinical research.

The degenerative ataxias are a very heterogeneous group of disorders that include numerous genetic diseases as well as apparently "sporadic" entities. There has been an explosion of discoveries related to genetic defects and related pathomechanisms that has brought us to the threshold of meaningful therapies in some but not all of these diseases. There also continues to be lack of knowledge of the causation of disease in a sizeable proportion of these patients.

Microglia in dementia with Lewy bodies.

Microglial activation (neuroinflammation) is often cited as a pathogenic factor in the development of neurodegenerative diseases. However, there are significant caveats associated with the idea that inflammation directly causes either α-synuclein pathology or neurofibrillary degeneration (NFD). We have performed immunohistochemical studies on microglial cells in five cases of dementia with Lewy bodies (DLB), median age 87, and nine cases of non-demented (ND) controls, median age 74, using tissue samples from the temporal lobe and the superior frontal gyrus.

Reduced responses to heroin-cue-induced craving in the dorsal striatum: effects of long-term methadone maintenance treatment.

Methadone maintenance treatment (MMT) is safe and effective for heroin addiction, but the neural basis of the length effects of long-term MMT on brain activity during craving in former heroin addicts is unclear. This study explored it by comparing the brain activations of heroin addicts with different length of MMT during pictorial presentation of heroin-related cue. Fifteen male former heroin addicts successfully treated by MMT less than 1 year (Group A), 15 matched patients with 2-3 year MMT (Group B) and 17 healthy controls underwent functional magnetic resonance imaging while heroin-related and neutral stimuli were present to them.

Human CNS immune senescence and neurodegeneration.

Microglial cells comprising the brain's immune system are essential for ensuring neuroprotection in the normal and pathological CNS. On the basis of histopathological observations in human brain, we believe that the ability of microglia to provide neuroprotection deteriorates as our brains get older and that such CNS immune senescence is a major factor contributing to the development of aging-related neurodegenerative diseases, notably Alzheimer's disease. The idea is consistent with the fact that immune senescence occurs naturally in the periphery, rendering the elderly people more susceptible to infections and cancers.

Presence of severe neuroinflammation does not intensify neurofibrillary degeneration in human brain.

This study investigated the allegedly causal relationship between microglial activation and neurofibrillary degeneration (NFD) typical of Alzheimer's disease (AD) by determining if presence of extreme microglial activation coincides with intensified NFD. We performed comparative histopathological analyses of NFD and microglial reactivity in 18 primary subjects ranging from 4 to 51 years of age. Ten of these subjects (median age 34) died from infectious disease (HIV, sepsis) and CNS trauma, while eight subjects (median age 32.

Alzheimer's disease, neuroprotection, and CNS immunosenescence.

This review is focused on discussing in some detail possible neuroprotective functions of microglial cells. We strive to explain how loss of these essential microglial functions might contribute toward the development of characteristic neuropathological features that characterize Alzheimer's disease. The conceptual framework guiding our thinking is provided by the hypothesis that microglial senescence accounts for impaired neuronal protection and consequent neurodegeneration.

Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms.

The nucleus accumbens, a site within the ventral striatum, plays a prominent role in mediating the reinforcing effects of drugs of abuse, food, sex, and other addictions. Indeed, it is generally believed that this structure mandates motivated behaviors such as eating, drinking, and sexual activity, which are elicited by natural rewards and other strong incentive stimuli. This article focuses on sex addiction, but we hypothesize that there is a common underlying mechanism of action for the powerful effects that all addictions have on human motivation.

Confirmation of the severe phenotypic effect of serine at codon 41 of the superoxide dismutase 1 gene.

Introduction: A Gly41Ser mutation in the superoxide dismutase 1 gene (SOD1) has been reported to cause a very rapid course of amyotrophic lateral sclerosis (ALS) in a limited number of Italian patients, but a Gly41Asp mutation results in a more benign course.

Methods: Four members of an African American family with autosomal dominant ALS were evaluated clinically over 12 years. Mutation analysis of SOD1 was done on 1 patient.

Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: a hypothesis.

Background: It is no surprise that it has taken over four decades to confirm and extend the crucial role of dopamine and related genes and gene deficits in the etiology of risk for drug dependence. Hundreds of studies, enabled by neuroscience neuroimaging and genetic advances, have been reported. While dopamine theories have been reported, confirmed, replicated and replicated again, changes have been slow to move from the bench to the bedside.

Neuronal progenitor transplantation and respiratory outcomes following upper cervical spinal cord injury in adult rats.

Despite extensive gray matter loss following spinal cord injury (SCI), little attention has been given to neuronal replacement strategies and their effects on specific functional circuits in the injured spinal cord. In the present study, we assessed breathing behavior and phrenic nerve electrophysiological activity following transplantation of microdissected dorsal or ventral pieces of rat fetal spinal cord tissue (FSC(D) or FSC(V), respectively) into acute, cervical (C2) spinal hemisections. Transneuronal tracing demonstrated connectivity between donor neurons from both sources and the host phrenic circuitry.

Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function.

To understand how microglial cell function may change with aging, various protocols have been developed to isolate microglia from the young and aged central nervous system (CNS). Here we report modification of an existing protocol that is marked by less debris contamination and improved yields and demonstrate that microglial functions are varied and dependent on age. Specifically, we found that microglia from aged mice constitutively secrete greater amounts of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) relative to microglia from younger mice and are less responsive to stimulation.

Respiratory neuroplasticity and cervical spinal cord injury: translational perspectives.

Paralysis of the diaphragm is a severe consequence of cervical spinal cord injury. This condition can be experimentally modeled by lateralized, high cervical lesions that interrupt descending inspiratory drive to the corresponding phrenic nucleus. Although partial recovery of ipsilateral diaphragm function occurs over time, recent findings show persisting chronic deficits in ventilation and phrenic motoneuron activity.

Microglial activation in the hippocampus of hypercholesterolemic rabbits occurs independent of increased amyloid production.

Background: Rabbits maintained on high-cholesterol diets are known to show increased immunoreactivity for amyloid beta protein in cortex and hippocampus, an effect that is amplified by presence of copper in the drinking water. Hypercholesterolemic rabbits also develop sporadic neuroinflammatory changes. The purpose of this study was to survey microglial activation in rabbits fed cholesterol in the presence or absence of copper or other metal ions, such as zinc and aluminum.

Formation of multinucleated giant cells and microglial degeneration in rats expressing a mutant Cu/Zn superoxide dismutase gene.

Background: Microglial neuroinflammation is thought to play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS). The purpose of this study was to provide a histopathological evaluation of the microglial neuroinflammatory response in a rodent model of ALS, the SOD1G93A transgenic rat.

Methods: Multiple levels of the CNS from spinal cord to cerebral cortex were studied in SOD1G93A transgenic rats during three stages of natural disease progression, including presymptomatic, early symptomatic (onset), and late symptomatic (end stage), using immuno- and lectin histochemical markers for microglia, such as OX-42, OX-6, and Griffonia simplicifolia isolectin B4.

Expression of TWIK-related acid sensitive K+ channels in capsaicin sensitive and insensitive cells of rat dorsal root ganglia.

Previous reports have demonstrated that small- to medium-diameter dorsal root ganglia (DRG) cells in rats can be subgrouped into individual cell types by patterns of voltage-activated currents. These cell types have consistent responses to algesic compounds and maintain characteristic histochemical phenotypes. Using immunocytochemical methods, we have now examined expression of TWIK (tandem of P domains in a weak inwardly rectifying K+ channel)-related acid sensitive K+ (TASK) channels, TASK-1, TASK-2 and TASK-3, in nine electrophysiologically identified small- to medium-diameter DRG cell types.