Neonatal brain inflammation enhances methamphetamine-induced reinstated behavioral sensitization in adult rats analyzed with explainable machine learning.

Neonatal brain inflammation produced by intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) results in long-lasting brain dopaminergic injury and motor disturbances in adult rats.

Downregulated Calcium-Binding Protein S100A16 and HSP27 in Placenta-Derived Multipotent Cells Induce Functional Astrocyte Differentiation.

Little is known about genes that induce stem cells differentiation into astrocytes. We previously described that heat shock protein 27 (HSP27) downregulation is directly related to neural differentiation under chemical induction in placenta-derived multipotent stem cells (PDMCs). Using this neural differentiation cell model, we cross-compared transcriptomic and proteomic data and selected 26 candidate genes with the same expression trends in both omics analyses.

Pioglitazone Ameliorates Lipopolysaccharide-Induced Behavioral Impairment, Brain Inflammation, White Matter Injury and Mitochondrial Dysfunction in Neonatal Rats.

Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.

Oxidative Stress and Neurodevelopmental Outcomes in Rat Offspring with Intrauterine Growth Restriction Induced by Reduced Uterine Perfusion.

Intrauterine growth restriction (IUGR) is a major cause of morbidity and mortality and is worldwide associated with delayed neurodevelopment. The exact mechanism involved in delayed neurodevelopment associated with IUGR is still unclear. Reduced uterine perfusion (RUP) is among the main causes of placental insufficiency leading to IUGR, which is associated with increases in oxidative stress.

Interleukin-1 receptor antagonist ameliorates the pain hypersensitivity, spinal inflammation and oxidative stress induced by systemic lipopolysaccharide in neonatal rats.

Perinatal inflammation-induced reduction in pain threshold may alter pain sensitivity to hyperalgesia or allodynia which may persist into adulthood. In this study, we investigated the anti-inflammatory protective effect of interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory cytokine, on systemic lipopolysaccharide (LPS)-induced spinal cord inflammation and oxidative stress, thermal hyperalgesia, and mechanical allodynia in neonatal rats. Intraperitoneal (i.

Systemic Lipopolysaccharide-Induced Pain Sensitivity and Spinal Inflammation Were Reduced by Minocycline in Neonatal Rats.

In this study, we investigated the effects of minocycline, a putative suppressor of microglial activation, on systemic lipopolysaccharide (LPS)-induced spinal cord inflammation, allodynia, and hyperalgesia in neonatal rats. Intraperitoneal (i.p.

Neuroprotective Effects of Intranasal IGF-1 against Neonatal Lipopolysaccharide-Induced Neurobehavioral Deficits and Neuronal Inflammation in the Substantia Nigra and Locus Coeruleus of Juvenile Rats.

Neonatal lipopolysaccharide (LPS) exposure-induced brain inflammation resulted in motor dysfunction and brain dopaminergic neuronal injury, and increased the risks of neurodegenerative disorders in adult rats. Our previous studies showed that intranasal administration of insulin-like growth factor-1 (IGF-1) protects against LPS-induced white matter injury in the developing rat brain. To further examine whether IGF-1 protects against LPS-induced brain neuronal injury and neurobehavioral dysfunction, recombinant human IGF-1 (rhIGF-1) at a dose of 50 µg/pup was administered intranasally 1 h following intracerebral injection of LPS (1 mg/kg) in postnatal day 5 (P5) Sprague-Dawley rat pups.

Suppression of HSP27 Restores Retinal Function and Protects Photoreceptors From Apoptosis in a Light-Induced Retinal Degeneration Animal Model.

Purpose: We used a light-induced retinal degeneration animal model to investigate possible roles of heat shock protein 27 (HSP27) in retinal/photoreceptor protection.

Methods: Sprague-Dawley rats were used for the light-induced retinal degeneration animal model. The histology of eye sections was observed for morphologic changes in the retina.

Knocking down of heat-shock protein 27 directs differentiation of functional glutamatergic neurons from placenta-derived multipotent cells.

This study presents human placenta-derived multipotent cells (PDMCs) as a source from which functional glutamatergic neurons can be derived. We found that the small heat-shock protein 27 (HSP27) was downregulated during the neuronal differentiation process. The in vivo temporal and spatial profiles of HSP27 expression were determined and showed inverted distributions with neuronal proteins during mouse embryonic development.

Melatonin reverses morphine tolerance by inhibiting microglia activation and HSP27 expression.

Aims: Melatonin has been reported to attenuate opioid tolerance. In this study, we explored the possible mechanism of melatonin in diminishing morphine tolerance.

Main Methods: Two intrathecal (i.

Erythropoietin Ameliorates Neonatal Hypoxia-Ischemia-Induced Neurobehavioral Deficits, Neuroinflammation, and Hippocampal Injury in the Juvenile Rat.

The hematopoietic growth factor erythropoietin (EPO) has been shown to be neuroprotective against hypoxia-ischemia (HI) in Postnatal Day 7 (P7)-P10 or adult animal models. The current study was aimed to determine whether EPO also provides long-lasting neuroprotection against HI in P5 rats, which is relevant to immature human infants. Sprague-Dawley rats at P5 were subjected to right common carotid artery ligation followed by an exposure to 6% oxygen with balanced nitrogen for 1.

Interleukin-1 receptor antagonist reduces neonatal lipopolysaccharide-induced long-lasting neurobehavioral deficits and dopaminergic neuronal injury in adult rats.

Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1β (IL-1β) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life.

IL-1 receptor antagonist attenuates neonatal lipopolysaccharide-induced long-lasting learning impairment and hippocampal injury in adult rats.

We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in an increase in interleukin-1β (IL-1β) content, injury to the hippocampus, and cognitive deficits in juvenile male and female rats, as well as female adult rats. The present study aimed to determine whether an anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), protects against the neonatal LPS exposure-induced inflammatory responses, hippocampal injury, and long-lasting learning deficits in adult rats. LPS (1 mg/kg) or LPS plus IL-1ra (0.

Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro.

Serotonin (5-hydroxytryptamine, 5-HT) has been implicated to play critical roles in early neural development. Recent reports have suggested that perinatal exposure to selective serotonin reuptake inhibitors (SSRIs) resulted in cortical network miswiring, abnormal social behavior, callosal myelin malformation, as well as oligodendrocyte (OL) pathology in rats. To gain further insight into the cellular and molecular mechanisms underlying SSRIs-induced OL and myelin abnormalities, we investigated the effect of 5-HT exposure on OL development, cell death, and myelination in cell culture models.

Differential roles of astrocyte and microglia in supporting oligodendrocyte development and myelination in vitro.

Oligodendrocyte (OL) development relies on many extracellular cues, most of which are secreted cytokines from neighboring neural cells. Although it is generally accepted that both astrocytes and microglia are beneficial for OL development, there is a lack of understanding regarding whether astrocytes and microglia play similar or distinct roles. The current study examined the effects of astrocytes and microglia on OL developmental phenotypes including cell survival, proliferation, differentiation, and myelination in vitro.

Effect of prenatal methadone on reinstated behavioral sensitization induced by methamphetamine in adolescent rats.

It has been known that methadone maintenance treatment is the standard treatment of choice for pregnant opiate addicts. However, there are few data on newborn outcomes especially in the cross talk with other addictive agents. The present study was to investigate the effect of prenatal exposure to methadone on methamphetamine (METH)-induced behavioral sensitization as an indicator of drug addiction in later life.

Neonatal exposure to lipopolysaccharide enhances accumulation of α-synuclein aggregation and dopamine transporter protein expression in the substantia nigra in responses to rotenone challenge in later life.

Brain inflammation in early life may enhance adult susceptibility to develop neurodegenerative disorders triggered by environmental toxins. Our previous studies show that perinatal lipopolysaccharide (LPS) exposure enhances adult susceptibility to rotenone-induced injury to the dopaminergic system in the substantia nigra (SN) of the adult rat brain. To further investigate the enhanced adult susceptibility by neonatal LPS exposure to rotenone neurotoxicity, we used our neonatal rat model of LPS exposure (1mg/kg, intracerebral injection in postnatal day 5, P5, neonatal rats) to examine the protein levels of α-synuclein and dopamine transporters (DAT) in the adult rat.

Celecoxib reduces brain dopaminergic neuronaldysfunction, and improves sensorimotor behavioral performance in neonatal rats exposed to systemic lipopolysaccharide.

Background: Cyclooxygenase-2 (COX-2) is induced in inflammatory cells in response to cytokines and pro-inflammatory molecules, suggesting that COX-2 has a role in the inflammatory process. The objective of the current study was to examine whether celecoxib, a selective COX-2 inhibitor, could ameliorate lipopolysaccharide (LPS)-induced brain inflammation, dopaminergic neuronal dysfunction and sensorimotor behavioral impairments.

Methods: Intraperitoneal (i.

Neonatal systemic exposure to lipopolysaccharide enhances susceptibility of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life.

Brain inflammation via intracerebral injection with lipopolysaccharide (LPS) in early life has been shown to increase risks for the development of neurodegenerative disorders in adult rats. To determine if neonatal systemic LPS exposure has the same effects on enhancement of adult dopaminergic neuron susceptibility to rotenone neurotoxicity as centrally injected LPS does, LPS (2 μg/g body weight) was administered intraperitoneally into postnatal day 5 (P5) rats and when grown to P70, rats were challenged with rotenone, a commonly used pesticide, through subcutaneous minipump infusion at a dose of 1.25 mg/kg/day for 14 days.

Nuclear condensation and cell cycle arrest induced by telomerase siRNA in neuroblastoma cells.

Neuroblastoma is a type of malignant extracranial tumor that occurs in children. Advanced neuroblastoma, and tumors with MYCN amplification in particular, have poor prognoses. Therefore, it is important to find an effective cure for this disease.

Mu-opioid receptor knockout mice are more sensitive to chlordiazepoxide-induced anxiolytic behavior.

We have previously demonstrated benzodiazepine binding in the cortex and hippocampus of mu-opioid receptor knockout (KO) mice. It is known that benzodiazepine receptors are involved in regulating anxiety-like behaviors. Thus, the present study was designed to examine whether there are changes in anxiety-like behavior in mice lacking mu-opioid receptors.

Involvement of Smac, p53, and caspase pathways in induction of apoptosis by gossypol in human retinoblastoma cells.

Purpose: Retinoblastoma is a malignant tumor of the retina usually occurring in young children. To date, the conventional treatments for retinoblastoma have been enucleation, cryotherapy, external beam radiotherapy, or chemotherapy. Most of these treatments, however, have possible side effects, including blindness, infections, fever, gastrointestinal toxicity, and neurotoxicity.

Naloxonazine, a specific mu-opioid receptor antagonist, attenuates the increment of locomotor activity induced by acute methamphetamine in mice.

Our previous studies indicated that the endogenous opioid system, particularly the mu-opioid receptor, may be involved in the modulation of methamphetamine (METH)-induced increases in locomotor behavior in mice. This study investigates the effects of naloxonazine, a specific mu-opioid receptor antagonist, on the locomotor behavioral response and phosphorylation pattern of dopamine and cAMP-regulated phosphoprotein of Mr32 (DARPP-32) in striatal dopaminergic transmissions induced by acute administration of METH to mice. Mice were injected with a single dose of naloxonazine (20 mg/kg, i.