Striatum Area Research Articles

MicroRNA-124-3p targets Sp1 transcription factor to regulate glioma progression in rats

Gliomas are the most prevalent malignancies of the central nervous system (CNS). Downregulation of microRNA‑124 (miR‑124) has been identified in glioma; however, its biological functions in glioma are not yet fully understood. Specificity protein 1 (SP1) is a type of transcription factor that is involved in cancer progression. In this study, we examined the targeting of Sp1 mRNA by miR-124-3p in a rat glioma model. After confirming and selecting the binding of Sp1 to miR-124 with the help of bioinformatics methods, adult male Wistar rats were used to induce glioma by microinjection of 1 × 106 C6 cells into the striatum area of brain. The rats were divided into 3 groups; intact, sham and glioma groups. The presence of glioma was confirmed 21 days after implantation through histological analysis. The expression levels of miR-124 and SP1 genes in the experimental groups were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Our data showed that the expression of miR-124 was significantly downregulated in glioma group compared to the sham and intact group, while the expression of SP1 was significantly upregulated. We found that the expression levels of miR-124 and Sp1 were decreased and increased in C6 cell line compared to the normal brain tissue cell line, respectively. The results indicated that Sp1 was identified as a direct target of miR‑124 through luciferase reporter assays. In summary, this study demonstrated for the first time that miR-124 expression is downregulated and Sp1 expression is upregulated in an animal model of glioma, which, in turn, may be involved in the development of glioma brain cancer.

Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson’s disease transgenic mouse

Dopamine (DA) plays a critical role in striatal motor control. The drop in DA level within the dorsal striatum is directly associated with the appearance of motor symptoms in Parkinson’s disease (PD). The progression of the disease and inherent disruption of the DA neurotransmission has been closely related to accumulation of the synaptic protein α-synuclein. However, it is still unclear how α-synuclein affects dopaminergic terminals in different areas of dorsal striatum. Here we demonstrate that the overexpression of human α-synuclein (h-α-syn) interferes with the striatal DA neurotransmission in an age‐dependent manner, preferentially in the dorsolateral striatum (DLS) of PDGF-h-α-syn mice. While 3-month-old mice showed an increase at the onset of h-α-syn accumulation in the DLS, 12-month-old mice revealed a decrease in electrically-evoked DA release. The enhanced DA release in 3-month-old mice coincided with better performance in a behavioural task. Notably, DA amplitude alterations were also accompanied by a delay in the DA clearance independently from the animal age. Structurally, dopamine transporter (DAT) was found to be redistributed in larger DAT-positive clumps only in the DLS of 3- and 12-month-old mice. Together, our data provide new insight into the vulnerability of DLS and suggest DAT-related dysfunctionalities from the very early stages of h-α-syn accumulation.

Sericin alleviates motor dysfunction by modulating inflammation and TrkB/BDNF signaling pathway in the rotenone-induced Parkinson’s disease model

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of nigrostriatal dopaminergic neurons and movement impairment. Based on theories, neuroinflammatory processes may be vital in the etiology of PD and other neurodegenerative diseases. Reports show that rotenone has neurotoxic, inflammatory, and motor impairment effects in PD. Sericin is a natural polymer with effective properties, such as neuroprotective and anti-inflammatory. Therefore, this study aimed to examine the effects of sericin administration on motor dysfunction by modulating inflammation and tyrosine kinase B/brain-derived neurotrophic factor (TrkB/BDNF) pathway in the rotenone-induced PD model.MethodsWistar male rats (3-months-old) were treated with rotenone (2 mg/kg every 48 h for 30 days) to induce a rotenone-induced PD model. Also, sericin was administered orally at dose of 200 mg/kg every 48 h for 30 days. Rotarod and bar tests were performed for motor dysfunction. The protein levels of BDNF, c-fos, TrkB, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6) and catalase activity were evaluated in the striatum area.ResultsResults showed that sericin increased latent time in the rotarod test and decreased the time staying on the pole in the bar test compared to the PD group (P < 0.001 for both tests). Moreover, sericin treatments decreased TNF-α (P < 0.001) and IL-6 (P < 0.001) concentration levels and enhanced the levels of BDNF (P < 0.001), c-fos (P < 0.001), TrkB (P < 0.001) proteins and catalase activity (P < 0.05) in the striatum area compared to the PD group.ConclusionThese results support a protective benefit of sericin therapy in a rotenone-induced PD paradigm by reducing motor impairment, inflammatory response, and disruption of the TrkB/BDNF signaling pathway.

Rapid Changes in the Expression of Active Caspase-3 and Glucocorticoid Receptors in Striatum Cells Induced by Neuroinflammation

Activation of microglia, resident immune cells of the central nervous system, plays a key role in the pathogenesis of neurological disorders induced by infections, as well as traumatic and ischemic events. Understanding the responses of brain cells, primarily microglial cells, to damaging effects can help overcome their pathological consequences. In this work, we analyzed the cellular effects of bacterial lipopolysaccharide (LPS), which is widely used as a pro-inflammatory stimulus. The injection of LPS into the area of right striatum of rats caused a pronounced neurological deficit in a day, which was accompanied by an increase in the number of microglial cells, an increase in the density of glucocorticoid receptors (GR) and their translocation into the nuclei of cells co-expressing the executive protease of apoptosis, active caspase-3 and GR, in the area of LPS injection. The results indicate acute changes in the activity of microglial cells, as well as in the expression and functional activity of GR in response to bacterial endotoxin. Further elucidation of the functional role of active caspase-3 and GR in microglial cells under conditions of pro-inflammatory activation may help identify targets for alleviating the symptoms of a neurological disorder.

The microbiota-gut-brain axis regulates motivation for exercise.

The microbiota-gut-brain axis regulates motivation for exercise.

The effect of thioredoxin-1 in a rat model of traumatic brain injury depending on diurnal variation.

Traumatic brain injury (TBI) is a public health concern with limited treatment options because it causes a cascade of side effects that are the leading cause of hospital death. Thioredoxin is an enzyme with neuroprotective properties such as antioxidant, antiapoptotic, immune response modulator, and neurogenic, among others; it has been considered a therapeutic target for treating many disorders. The controlled cortical impact (CCI) model was used to assess the effect of recombinant human thioredoxin 1 (rhTrx1) (1 μg/2 μL, intracortical) on rats subjected to TBI at two different times of the light-dark cycle (01:00 and 13:00h). We analyzed the food intake, body weight loss, motor coordination, pain perception, and histology in specific hippocampus (CA1, CA2, CA3, and Dental Gyrus) and striatum (caudate-putamen) areas. Body weight loss, reduced food intake, spontaneous pain, motor impairment, and neuronal damage in specific hippocampus and striatum regions are more evident in rats subjected to TBI in the light phase than in the dark phase of the cycle and in groups that did not receive rhTrx1 or minocycline (as positive control). Three days after TBI, there is a recovery in body weight, food intake, motor impairment, and pain, which is more pronounced in the rats subjected to TBI at the dark phase of the cycle and those that received rhTrx1 or minocycline. Knowing the time of day a TBI occurs in connection to the neuroprotective mechanisms of the immune response in diurnal variation and the usage of the Trx1 protein might have a beneficial therapeutic impact in promoting quick recovery after a TBI.

Chronic intermittent ethanol exposure differentially alters the excitability of neurons in the orbitofrontal cortex and basolateral amygdala that project to the dorsal striatum

Alcohol use disorder is associated with altered neuron function including those in orbitofrontal cortex (OFC) and basolateral amygdala (BLA) that send glutamatergic inputs to areas of the dorsal striatum (DS) that mediate goal and habit directed actions. Previous studies reported that chronic intermittent (CIE) exposure to ethanol alters the electrophysiological properties of OFC and BLA neurons, although projection targets for these neurons were not identified. In this study, we used male and female mice and recorded current-evoked spiking of retrobead labeled DS-projecting OFC and BLA neurons in the same animals following air or CIE treatment. DS-projecting OFC neurons were hyperexcitable 3- and 7-days following CIE exposure and spiking returned to control levels after 14 days of withdrawal. In contrast, firing was decreased in DS-projecting BLA neurons at 3-days withdrawal, increased at 7- and 14-days and returned to baseline at 28 days post-CIE. CIE exposure enhanced the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) of DS-projecting OFC neurons but had no effect on inhibitory postsynaptic currents (sIPSCs). In DS-projecting BLA neurons, the amplitude and frequency of sIPSCs was enhanced 3 days post-CIE with no change in sEPSCs while at 7-days post-withdrawal, sEPSC amplitude and frequency were increased and sIPSCs had returned to normal. Finally, in CIE-treated mice, acute ethanol no longer inhibited spike firing of DS-projecting OFC and BLA neurons. Overall, these results suggest that CIE-induced changes in the excitability of DS-projecting OFC and BLA neurons could underlie deficits in behavioral control often observed in alcohol-dependent individuals.

D-685 Reverses Motor Deficits and Reduces Accumulation of Human α-Synuclein Protein in Two Different Parkinson's Disease Animal Models.

Aggregation of misfolded α-synuclein (α-syn) protein in the periphery and central nervous system (CNS) gives rise to a group of disorders, which are labeled collectively as synucleinopathies. These clinically distinct disorders are known as pure autonomic failure, Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). In the case of PD, it has been demonstrated that toxic aggregates of α-syn protein not only cause apoptosis of dopamine neurons but its accumulation in the neocortex and limbic area principally contributes to dementia. In our multifunctional drug discovery research for PD, we converted one of our catechol-containing lead dopamine agonist molecules D-520 into its prodrug D-685. The prodrug exhibited higher in vivo anti-Parkinsonian efficacy in a reserpinized PD animal model than the parent D-520 and exhibited facile brain penetration. In our study with an α-syn transgenic animal model (D line) for PD and dementia with Lewy bodies (DLB), we have shown that 1 month of chronic treatment with the compound D-685 was sufficient to reduce the accumulation of α-syn and phospho-α-syn in the cortex, hippocampus, and striatum areas significantly compared to the control tg mice. Furthermore, D-685 did not exhibit any deleterious effect in the CNS as was evident from the neuron and microglia studies. Future studies will further explore in depth the potential of D-685 to modify disease progression while addressing symptomatic deficits.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

The effect of acute mental stress on the exchange of monoamines in the mesocortical and nigrostriatal systems of the rat brain

Background. Мesocortical and nigrostriatal dopaminergic systems are highly sensitive to stressful events. One of the most adequate models of acute psychogenic stress in animals is the death of a partner upon presentation of a predator.&#x0D; Aim. To study the content of dopamine (DA), serotonin and their metabolites: dioxyphenylacetic (DOPAC), homovanillic and 5-hydroxyindoleacetic (5-HIAA) acids in the prefrontal cortex, striatum, and ventral tegmental area in rats on days 3, 7, and 14 after the acute psychogenic stress of the death of a partner upon presentation of a predator.&#x0D; Materials and methods. 28 male Wistar rats were studied. Acute single psychotraumatic situation was used. A group of rats was placed in a tiger python terrarium. One animal died as a result of its nutritional needs, the rest of the rats experienced the death of a partner. The content of monoamines in the brain structures was carried out by high performance liquid chromatography with electrochemical detection.&#x0D; Results. Changes in the content of monoamines in the prefrontal cortex, striatum, and ventral tegmental area were found on the 7 and 14 days after the presentation of the predator. In the ventral tegmental area on the 7 day, there was an increase in the DOPAC/DA ratio and an increase in the serotonin metabolite 5-HIAA, which reflects an increase in the activity of dopamine and serotonin. In the prefrontal cortex on the 14 day, the DOPAС content and the DOPAС/DA index decreased. The 5-HIAA content in the prefrontal cortex and the 5-HIAA/5-HT value also significantly decreased.&#x0D; Conclusions. Changes in the metabolism of monoamines after presentation of a predator develop gradually: increase of the dopamine and serotonin activity in the ventral tegmental area was noted on the 7 day after presentation of the predator, decrease in their activity in the striatum and prefrontal cortex only on the 14 day, reflecting the development of depressive states and post-traumatic stress disorder.

Abnormal functional connectivity of the striatum in first-episode drug-naive early-onset Schizophrenia.

Abnormal brain network connectivity is strongly implicated in the pathogenesis of schizophrenia. The striatum, consisting of the caudate and putamen, is the major treatment target for antipsychotics, the primary treatments for schizophrenia; however, there are few studies on the functional connectivity (FC) of striatum in drug‐naive early‐onset schizophrenia (EOS) patients. We examined the FC values of the caudate nucleus and putamen with whole brain by resting‐state functional magnetic resonance imaging (RS‐fMRI) and the associations with indices of clinical severity. Patients demonstrated abnormal FC between subregions of the putamen and both the visual network (left middle occipital gyrus) and default mode network (bilateral anterior cingulate, left superior frontal, and right middle frontal gyri). Furthermore, FC between dorsorostral putamen and left superior frontal gyrus correlated with both positive symptom subscore and total score on the Positive and Negative Syndrome Scale (PANSS). These findings demonstrate abnormal FC between the striatum and other brain areas even in the early stages of schizophrenia, supporting neurodevelopmental disruption in disease etiology and expression.

Motor, memory, and anxiety-like behavioral impairments associated with brain-derived neurotrophic factor and dopaminergic imbalance after inhalational exposure to deltamethrin

Believed to cause damage to the nervous system and possibly being associated with neurodegenerative diseases, deltamethrin (DM) is a type II pyrethroid used in pest control, public health, home environment, and vector control. The objective of this study was to evaluate the motor, cognitive and emotional changes associated with dopaminergic and BDNF imbalance after DM exposure in rats. Sixty Wistar rats (9–10 months-old) were used, under Ethics Committee on Animal Research license (ID 19/2017). The animals were randomly divided into four groups: control (CTL, 0.9% saline), DM2 (2 mg DM in 1.6 mL 0.9% saline), DM4 (4 mg of DM in 1.6 mL of 0.9% saline), and DM8 (8 mg of DM in 1.6 mL of 0.9% saline). DM groups were submitted to 9 or 15 inhalations, one every 48 h. Half of the animals from each group were randomly selected and perfused 24 h after the 9th or 15th inhalation. Throughout the experiment, the animal’s behavior were evaluated using catalepsy test, open field, hole-board test, Modified Elevated Plus Maze, and social interaction. At the end of the experiments, the rats were perfused transcardially and their brains were processed for Tyrosine Hydroxylase (TH) and Brain derived neurotrophic factor (BDNF) immunohistochemistries. The animals submitted to 9 inhalations of DM showed a reduction in immunoreactivity for TH in the Substantia nigra pars compacta (SNpc), ventral tegmental area (VTA), and dorsal striatum (DS) areas, and an increase in BDNF in the DS and CA1, CA3 and dentate gyrus (DG) hippocampal areas. Conversely, the animals submitted to 15 inhalations of DM showed immunoreactivity reduced for TH in the SNpc and VTA, and an increase in BDNF in the hippocampal areas (CA3 and DG). Our results indicate that the DM inhalation at different periods induce motor and cognitive impairments in rats. Such alterations were accompanied by dopaminergic system damage and a possible dysfunction on synaptic plasticity.

Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation

BackgroundObsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls.ResultsThere were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences.ConclusionsDNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.

Neuroinflammatory penumbra in Parkinson’s disease

To date, the etiology and pathogenesis of Parkinson’s disease (PD) are not fully understood. In this publication, we present a critical review of the available international data on the involvement of inflammation processes in the etiopathogenesis of the disease in the context of our research results. The data obtained by us during modeling of parkinsonian syndrome of neuroinflammatory origin (lipopolysaccharide endotoxin was used) in laboratory rats (basic group, n = 21; control group, n = 7) indicate that intranasal administration of lipopolysaccharide in all three studied doses (1, 10 and 100 μg/kg/ml) seven days after the end of the experiment (21 injections) causes the same moderate morphological degenerative and inflammatory changes in the histostructure of the substantia nigra, extending to the striatum area (p &gt; 0.05). This fact can be best explained by the all-or-none law. The staged, sequential transition of primary reversible (neuroinflammatory) pathomorphological changes to secondary irreversible (neurodegenerative) ones in PD, as well as secondary activation of microglia during neuronal degeneration, allows proposing the term “neuroinflammatory penumbra”, which will best help understand the pathogenesis of the disease and the development of therapies that change the course of Parkinson’s disease. Our data on the use of mesenchymal multipotent stromal cells in rats with neurotoxic (rotenone) parkinsonian syndrome (n = 10) and in PD individuals (n = 10) demonstrate a decrease in motor impairment, overall improvement of patients and an effect on laboratory parameters compared with control groups. We associate the early positive effect, observed already in the first week after the administration of mesenchymal multipotent stromal cells, with their paracrine action, including on the neuroinflammatory penumbra.

Prominent Striatum Amyloid Retention in Early-Onset Familial Alzheimer's Disease With PSEN1 Mutations: A Pilot PET/MR Study.

Background: With the advancements of amyloid imaging in recent years, this new imaging diagnostic method has aroused great interest from researchers. Till now, little is known regarding amyloid deposition specialty in patients with early-onset familial Alzheimer's disease (EOFAD), and even less is known about its role in cognitive impairments.Objectives: Our study aimed to evaluate the amyloid deposition in five patients with EOFAD, 15 patients with late-onset sporadic AD, and 12 healthy subjects utilizing 11C-labeled Pittsburgh compound-B (11C-PiB) amyloid PET imaging. Moreover, we figured out the correlation between striatal and cortical standardized uptake value ratios (SUVRs). We also investigated the correlation between 11C-PiB retention and cognitive presentation.Results: All patients with EOFAD showed high amyloid deposition in the striatum, a pattern that is not usually seen in patients with late-onset sporadic AD. The SUVR in the striatum, especially in the amygdala, showed significant correlations with cortex SUVR in EOFAD. However, neither striatal nor cortical 11C-PiB retention was related to cognitive decline.Conclusions: The amyloid distribution in patients with EOFAD differs from late-onset sporadic AD, with higher amyloid deposits in the striatum. Our study also demonstrated positive correlations in 11C-PiB retention between the striatum and other cortical areas. We revealed that the distribution of amyloid in the brain is not random but diffuses following the functional and anatomical connections. However, the degree and pattern of amyloid deposition were not correlated with cognitive deficits.

FV 8. The effect of repeated blocks of intermittant theta burst stimulation (iTBS) over the dorsolateral prefrontal cortex (dlPFC) on fronto-striatal connectivity. A 18F-DesmethoxyFallypride (DMFP) Positron Emission Tomography study (PET)

Background. Frontostriatal networks are neural pathways formed between frontal lobe regions and striatum that is involved in cognitive and behavioural processes. Transcranial Magnetic Stimulation (TMS) is able to modulate connectivity in the human brain and it is widely used for clinical purposes to treat depression patients. This exploratory PET and TMS multimodal study would contribute to better understand the role of striatal dopaminergic neurotransmission in the fronto-striatal area. Objective. The main objective of the study is to investigate the fronto-striatal connectivity by measuring the release of dopamine in the striatum in response to an excitatory intermittent theta burst stimulation (iTBS) of the left-dlPFC. A PET measurement was performed by using the 18F-DesmethoxyFallypride (DMFP) radioligand, that is a high affinity receptor-antagonist which competes with endogenous Dopamine neurotransmitters for D2/D3 receptor binding. Methods. The study was conducted on 23 healthy participants, who underwent iTBS sham (control) and verum stimulations on separate days. The PET scan lasted 120 mins, consisting of 4 iTBS stimulations delivered to the left-DLPFC at 30 mins interval. In verum stimulation, 90% of resting motor threshold (rMT) was used as the stimulation intensity. The excitatory iTBS protocol is delivered in a sequence of trains (burst of 10 pulses in 2 secs having inter train interval of 8 secs), with a total duration of 190 secs. PET dynamic data was analysed using reference region method in which cerebellum was used as the reference region (due to lack of D2-D3 receptors). Binding Potentials (BP) are the main outcome measure representing the ligand binding which is inversely proportional to the Dopamine (DA) levels.Mean Binding Potentials in the sub-regions of the striatum (Nucleus Caudate and Putamen) were compared between the sham and verum stimulation using analysis of variance (ANOVA). Results. iTBS stimulation of the left DLPFC increased the dopamine release (as reflected by BPs) in the striatum areas (putamen and nucleus caudate) in the verum stimulation, as compared to sham stimulation.Although the increase in dopamine release did not differ between the first block of stimulation, we observed significant increase after two, three and fourth blocks of stimulation. Conclusion. Our data suggest that the efficiency of iTBS protocol can effectively enhance fronto-striatal connectivity by applying a higher number of stimuli (i.e., 3rd & 4th TMS block but not 1st-& 2nd block). This minimal time stimulation protocol can be used as a therapy for treating Depression patients by presenting it in the repeated blocks of short intervals. This scheme could prevent the long stimulation protocols, and be less painful. Fig. 1. Figure represents the statistically significant main effect of TMS . The verum stimulation shows a reduction of 8.6% [18F]DMFP Binding Potential as compared to the sham stimulation. Fig. 2. Percentage reduction in [18F] desmethoxyfallypride-binding potentials extracted from the difference of sham and verum stimulation in healthy subjects. Dose-dependent iTBS aftereffects seem to be more pronounced at 3rd block and 4th block respectively as compared to 1st and 2nd block of TMS.

Effect of Pramipexole on Inflammatory Response in Central Nervous System of Parkinson's Disease Rat Model

Pramipexole is the dopamine receptor agonist commonly used for treatment of PD, the effect of which on immunity played an important role in pathological process is also deserved to be further studied. We observed the effect of pramipexole on behavior and central nervous system (CNS) inflammatory cytokines of Parkinson's Disease (PD) model rats. We injected 3.0 μL lipopolysaccharide into the right substantia nigra compact (SNc) and ventral tegmental area (VTA) of sprague-dawley (SD) rats to establish PD models which were divided as treated group feeded with pramipexole for 14 d and untreated group feeded with saline. And SD rats were selected as control group feeded with saline. We conducted rotation test on PD model rats before and after treatment. We also performed euthanasia on all rats to obtain the striatum area and nearby tissues after treatment, measuring mRNA expression and concentration of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by reverse transcription polymerase chain reaction test and elisa method, respectively. It was observed that the degree of behavior improvement in treated group was greater than that in untreated group. In addition, mRNA expression and concentrations of IL-6 and TNF-α in treated group were lower than those in untreated group and higher than those in control group. Pramipexole improved behavior of PD model rat, and down regulated the mRNA expression and concentrations of IL-6 and TNF-α in their CNS.

Gray Matter Abnormalities of Orbitofrontal Cortex and Striatum in Drug-Naïve Adult Patients With Obsessive-Compulsive Disorder.

Objective: This study examined whether obsessive-compulsive disorder (OCD) patients have gray matter abnormalities in regions related to executive function, and whether such abnormalities are associated with impaired executive function.Methods: Multiple scales were administered to 27 first-episode drug-naïve OCD patients and 29 healthy controls. Comprehensive brain morphometric indicators of orbitofrontal cortex (OFC) and three striatum areas (caudate, putamen, and pallidum) were determined. Hemisphere lateralization index was calculated for each region of interest. Correlations between lateralization index and psychological variables were examined in OCD group.Results: The OCD group had greater local gyrification index for the right OFC and greater gray matter volumes of the bilateral putamen and left pallidum than healthy controls. They also had weaker left hemisphere superiority for local gyrification index of the OFC and gray matter volume of the putamen, but stronger left hemisphere superiority for gray matter volume of the pallidum. Patients' lateralization index for local gyrification index of the OFC correlated negatively with Yale-Brown Obsessive Compulsive Scale and Dysexecutive Questionnaire scores, respectively.Conclusion: Structural abnormalities of the bilateral putamen, left pallidum, and right OFC may underlie OCD pathology. Abnormal lateralization in OCD may contribute to the onset of obsessive-compulsive symptoms and impaired executive function.

Magnetic Targeting of Human Olfactory Mucosa Stem Cells Following Intranasal Administration: a Novel Approach to Parkinson's Disease Treatment.

Among the various therapeutic procedures used for improving PD, stem cell-based therapy has been shown to be a promising method. Olfactory ectomesenchymal stem cells (OE-MSCs) are a great source of stem cells for PD. Also, the intranasal administration (INA) of stem cells to the neural lesion has several advantages over the other approaches to cellular injections. However, improving the efficacy of INA to produce the highest number of cells at the lesion site has always been a controversial issue. For this purpose, this study was designed to apply the magnetically targeted cell delivery (MTCD) approach to OE-MSCs in the injured striatum area through the IN route in order to explore their outcomes in rat models of PD. Animals were randomly classified into four groups including control, PD model, treatment-NTC (treated with INA of non-target cells), and treatment-TC (treated with INA of target cells). The Alg-SPIONs-labeled OE-MSCs were stained successfully using the Prussian blue method with an intracellular iron concentration of 2.73 pg/cell. It was able to reduce signal intensity in the striatum region by increasing the number of these cells, as shown by the magnetic resonance imaging (MRI). Behavioral evaluation revealed that the administration of OE-MSCs with this novel advanced stem cell therapy alleviated Parkinson's motor dysfunction. Further, histological evaluations confirmed the functional enhancement of dopaminergic neuron cells by the expression of Nurr1, Dopamine transporter (DAT), and paired-like homeodomain transcription factor 3 (TH). Overall, this study showed that INA of OE-MSCs in the MTCD approach enhanced stem cells' therapeutic effects in PD models.

Chronic feeding with 3% dried raw blueberries (V. corymbosum) reduces apomorphine-induced rotations and striatal dopaminergic loss in hemiparkinsonian rats

Blueberries (BB) are rich in antioxidant polyphenols, and their intake could prevent Parkinson’s disease (PD). Here we assessed whether rats chronically fed dried raw BB develop resistance to dopaminergic denervation and motor disorders caused by unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), a dopaminergic neurotoxin acting mainly by inducing oxidative stress. Male rats were fed either with LabDiet® alone or supplemented with 3% lyophilized raw BB for 2 weeks before and 3 weeks after injecting 6-OHDA (day 0) or vehicle (mock lesion) into the right striatum. The cylinder test was performed on days −14, −7, −1, +7, +14, and +21; the percentage of ipsilateral forepaw (IF) use asymmetry was determined by counting the wall contacts made with either forepaw or with both. Apomorphine (0.25 mg/kg, s.c.)-induced rotation was performed on days −1, +7, +14, and +21. Full contralateral rotations were counted in 3-min periods, every 15 min, up to 90 min. Striatal slices were immunostained for tyrosine hydroxylase (TH) and the ionized calcium-binding protein-1 adapter (Iba1) [immunoreactive area or microglia count in right striatum expressed as % of the left striatum]. Antioxidants in BB methanolic extracts neutralized the free radical 2,2-diphenyl-1-picrylhydrazyl in a concentration-dependent manner. Anthocyanins have been reported as the most abundant polyphenols in BB. Using the pH differential method, the total anthocyanin content (malvidin-3-glucoside equivalents) in raw BB averaged 21.04 mg/g dry weight. The range of anthocyanin intake by rats throughout the study varied from 37.7 to 72.2 mg/kg body weight. The time and food type factors, as well as their interaction were significant according to two-way RM-ANOVA in both the apomorphine-induced rotations and the cylinder test. Compared with LabDiet® alone, chronic supplementation with 3% dried raw BB decreased apomorphine-induced rotations on days +14 and +21 (p < 0.001) and produced a 46% reduction in total rotations post-surgery (p < 0.05), but only caused a partial, non-significant, decrease of IF asymmetry. BB supplementation reduced TH loss in the striatum (p < 0.05) but did not attenuate the increase of Iba1+ microglia. The consumption of 3% dried raw blueberries attenuates dopaminergic denervation and partially reverses motor disorders in the 6-OHDA-induced PD model in rats. The phytochemicals of raw blueberries that contribute to the observed neuroprotective effect are yet to be identified.