Pre-frontal parvalbumin interneurons in schizophrenia: a meta-analysis of post-mortem studiesAbstract
Parvalbumin interneurons are fast-spiking GABAergic neurons that provide inhibitory control of cortical and subcortical circuits and are thought to be a key locus of the pathophysiology underlying schizophrenia. In view of the contradictory results regarding the nature of parvalbumin post-mortem findings in schizophrenia, we conducted a quantitative meta-analysis of the data on parvalbumin cell density and parvalbumin mRNA levels in pre-frontal regions in the brains of patients with schizophrenia (n = 274) compared with healthy controls (n = 275). The results suggest that parvalbumin interneurons are reduced in density in the frontal cortex of patients with schizophrenia (Hedges’ g = − 0.27; p = 0.03) and there is a non-significant reduction in parvalbumin mRNA levels (g = − 0.44; p = 0.12). However, certain methodological issues need to be considered in interpreting such results and are discussed in more detail. A meta-regression was conducted for post-mortem interval and year of publication as covariates which were both non-significant, except in the mRNA meta-analysis where post-mortem interval was found to be significant. Overall our findings provide tentative support for the hypothesis that the GABAergic system is deficient in schizophrenia and that parvalbumin-containing interneurons offer a potential target for treatment. However, further well-controlled studies that examine multiple regions and layers are warranted to determine whether parvalbumin alterations are region or layer specific and to test the robustness of the findings further.
|
Molecular determinants of behavioral changes induced by neonatal ketamine and dexmedetomidine applicationAbstract
Ketamine (KET), an anesthetic, analgesic, and a sedative N-methyl-d-aspartate (NMDA) receptor antagonist agent, exposure during neonatal period may lead to learning impairment, behavioral abnormalities, and cognitive decline in the later years of life. In recent studies, it has been reported that sedative-acting α2 agonist dexmedetomidine (DEX), which is commonly used in clinical practice with KET, has neuroprotective effects and prevents the undesirable effects of anesthesia. To elucidate the underlying mechanisms of these actions, we investigated the interaction between NMDA receptors α2 adrenoceptor and adulthood behaviors in neonatally KET and/or DEX administrated mice. Balb/c male mice were administrated with saline, KET (75 mg/kg), DEX (10 µg/kg), or KET + DEX (75 mg/kg + 10 µg/kg) on postnatal day 7. During adulthood (8–10 weeks old) mice were subjected to elevated plus maze, open field, and Morris water maze tests. After behavioral tests, hippocampus samples were extracted for mRNA expression studies of NMDAR subunits (GluN1, GluN2A, and GluN2B) and α2 adrenoceptor subunits (α2A, α2B, and α2C) by real-time PCR. Ketamine increased horizontal and vertical locomotor activity (p < 0.01) and impaired spatial learning-memory (p < 0.05). DEX increased anxiety-like behavior (p < 0.01), but did not affect spatial learning-memory and locomotor activity. KET + DEX impaired spatial learning-memory (p < 0.01), increased horizontal locomotor activity (p < 0.01), and anxiety-like behavior (p < 0.05). Our study implies that DEX cannot prevent the adverse effects of KET, on spatial learning-memory, and locomotor activity. In addition to this, it can be thought that during brain development, there is an interaction between NMDAR and α2 adrenoceptor systems.
|
Hyposmia as a marker of (non-)motor disease severity in Parkinson’s diseaseAbstract
The aim of this study was to evaluate the relationship of hyposmia in Parkinson’s disease (PD) with other motor and non-motor symptoms and with the degree of nigrostriatal dopaminergic cell loss. A total of 295 patients with a diagnosis of PD were included. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Motor symptoms were rated using the Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS III). To evaluate other non-motor symptoms, we used the Mini-Mental State Examination (MMSE) as a measure of global cognitive function and validated questionnaires to assess sleep disturbances, psychiatric symptoms, and autonomic dysfunction. A linear regression model was used to calculate correlation coefficients between UPSIT score and motor and non-motor variables [for psychiatric symptoms a Poisson regression was performed]. In a subgroup of patients (n = 155) with a dopamine transporter (DaT) SPECT scan, a similar statistical analysis was performed, now including striatal DaT binding. In the regression models with correction for age, sex, disease duration, and multiple testing, all motor and non-motor symptoms were associated with UPSIT scores. In the subgroup of patients with a DaT-SPECT scan, there was a strong association between olfactory test scores and DaT binding in both putamen and caudate nucleus. Hyposmia in PD is associated with various motor and non-motor symptoms, like cognition, depression, anxiety, autonomic dysfunction and sleep disturbances, and with the degree of nigrostriatal dopaminergic cell loss. This finding adds further confirmation that hyposmia holds significant promise as a marker of disease progression.
|
What goes up must come down: insights from studies on descending controls acting on spinal pain processingAbstract
Descending controls link higher processing of noxious signals to modulation of spinal cord responses to their noxious inputs. It has become possible to study one key inhibitory system in animals and humans using one painful stimulus to attenuate another distant response and so eliciting diffuse noxious inhibitory controls (DNIC) or the human counterpart, conditioned pain modulation (CPM). Here, we discuss the neuronal pathways in both species, their pharmacology and examine changes in descending controls with a focus on osteoarthritis. We will also discuss the opposing descending facilitatory system. Strong parallels between DNIC and CPM emphasize the possibility of forward and reverse translation.
|
Late-onset Niemann–Pick disease type C overlapping with frontotemporal dementia syndromes: a case reportAbstract
The diagnosis of adult-onset Niemann–Pick disease type C (NPC) could be difficult because its primary symptoms [dementia and vertical supranuclear gaze palsy (VSGP)] are mainly seen in neurodegenerative dementias and progressive supranuclear palsy (PSP). Our patient with dementia and asymmetric parkinsonism resembled corticobasal syndrome and after the appearance of VSGP, the criteria of PSP were fulfilled too. Cerebellar symptoms appeared late during the course of the disease, leading to the diagnosis of NPC at the age of 59 years.
|
FGF2 and dual agonist of NCAM and FGF receptor 1, Enreptin, rescue neurite outgrowth loss in hippocampal neurons expressing mutated huntingtin proteinsAbstract
In the present study, we developed an in vitro model of Huntington disease (HD) by transfecting primary rat hippocampal neurons with plasmids coding for m-htt exon 1 with different number of CAG repeats (18, 50 and 115) and demonstrated the influence of the length of polyQ sequence on neurite elongation. We found that exogenously applied FGF2 significantly rescued the m-htt-induced loss of neurite outgrowth. Moreover, the Enreptin peptide, an FGFR1 and NCAM dual agonist, had a similar neuritogenic effect to FGF2 in clinically relevant m-htt 50Q-expressing neurons. This study has developed an in vitro model of primary hippocampal neurons transfected with m-htt-coding vectors that is a powerful tool to study m-htt–related effects on neuronal placticity.
|
Subthalamic nucleus deep brain stimulation improves dyskinesias in Parkinson’s disease beyond levodopa reductionAbstract
Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves motor fluctuations and dyskinesias in patients with Parkinson's disease (PD). Dyskinesia improvement with STN DBS is believed to result entirely from levodopa reduction. However, some studies suggest that STN DBS may also directly suppress dyskinesias. To determine whether bilateral STN DBS improves dyskinesias beyond what would be expected from levodopa reduction alone, we analyzed pre-operative and post-operative dyskinesia scores (sum of MDS-UPDRS items 4.1 and 4.2) from 61 PD patients with bilateral STN DBS. A multiple regression model (adjusted for disease severity, disease duration, active contacts above the STN, use of amantadine, high pre-operative levodopa-equivalent dose (LED), sex, and interaction between active contacts above the STN and amantadine use) was created to describe the relationship between dyskinesia scores and LED prior to DBS. Using this model, a post-operative dyskinesia score was estimated from post-operative LED and compared to the actual post-operative dyskinesia score. The regression model was statistically significant overall (p = 0.003, R2 = 0.34, adjusted R2 = 0.24). The actual post-operative dyskinesia score (1.0 ± 1.4) was significantly lower than the score predicted by the model (3.0 ± 1.1, p < 0.0001). Dyskinesias after STN DBS improved more than predicted by levodopa reduction alone. Our data support the idea that STN stimulation may directly improve dyskinesias.
|
PKC inhibitor reversed the suppressive effect of orexin-A on IPSCs of locus coeruleus neurons in naloxone-induced morphine withdrawalAbstract
The locus coeruleus (LC) as a target of addictive drugs receives a dense projection of orexinergic fibres from the lateral hypothalamus (LH) and is accordingly a candidate site for the expression of the somatic aspects of morphine withdrawal. Recently it has been shown that the inhibitory synaptic currents of LC neurons decrease partly through orexin type 1 receptors in the context of naloxone-induced morphine withdrawal; however, its cellular mechanism remains unclear. In this study, whole-cell patch clamp recordings of LC neurons in brainstem slices were used to investigate the impact of protein kinase C (PKC) on GABAergic inhibitory post-synaptic currents (IPSCs) in the context of naloxone-induced morphine withdrawal. Male Wistar rats (P14–P21) received morphine (20 mg/kg, i.p.) daily for 7 consecutive days to induce morphine dependency. Our results showed that the application of PKC inhibitor (Go 6983; 1 µM) alone did not decrease the probability of GABA release in the LC neurons of the morphine-treated rats in the presence of naloxone. Although, Go 6983 reversed the reduction of the amplitude of evoked IPSCs (eIPSCs) and spontaneous IPSCs (sIPSCs) frequency induced by orexin-A but did not change the sIPSCs amplitude. These results indicate that the suppressive effect of orexin-A on IPSCs is probably reversed by PKC inhibitor in the LC neurons of morphine-treated rats in the context of naloxone withdrawal.
|
Cortical plasticity as synaptic mechanism for chronic painAbstract
Adult brain structures such as the hippocampus are highly plastic to learning and gaining new experiences. Recent studies reveal that cortical areas that respond to sensory noxious stimuli (stimuli that cause pain in humans) are also highly plastic, like the learning-related hippocampus. Long-term potentiation (LTP), a key cellular model for learning and memory, is reported in the anterior cingulate cortex (ACC) and insular cortex (IC), two key cortical areas for pain perception. ACC and IC LTP exist in at least two major forms: presynaptically expressed LTP, and postsynaptically expressed LTP (post-LTP). In this short review, I will review, recent progress made in cortical LTPs, and explore potential roles of other forms of LTPs such as synaptic tagging. Their contribution to chronic pain as well as emotional changes caused by injury will be discussed.
|
Role of the protease-activated receptor 1 in regulating the function of glial cells within central and peripheral nervous systemAbstract
Protease-activated receptor 1 (PAR1) is a cell surface receptor, which belongs to a family of G protein-coupled receptors and signals in response to multiple extracellular proteases. PAR1 is widely distributed in mammalian cells and tissues, including human glial cells. Within this context, PAR1 may participate to various activities promoted by glial cells. In fact, glia does not represent merely a glue in the nervous system but affects significantly various neuronal functions and activities being also significantly involved in the pathophysiology of various nervous system disorders. In this review, we summarize the current understanding of PAR1 expression and functions within glial cells both in the central and peripheral nervous system.
|
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Πληροφορίες
Ετικέτες
Δευτέρα 23 Σεπτεμβρίου 2019
Αναρτήθηκε από
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
στις
2:10 π.μ.
Ετικέτες
00302841026182,
00306932607174,
alsfakia@gmail.com,
Anapafseos 5 Agios Nikolaos 72100 Crete Greece,
Medicine by Alexandros G. Sfakianakis
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Αρχειοθήκη ιστολογίου
-
►
2023
(276)
- ► Φεβρουαρίου (133)
- ► Ιανουαρίου (143)
-
►
2022
(1976)
- ► Δεκεμβρίου (116)
- ► Σεπτεμβρίου (158)
- ► Φεβρουαρίου (165)
- ► Ιανουαρίου (161)
-
►
2021
(3661)
- ► Δεκεμβρίου (161)
- ► Σεπτεμβρίου (274)
- ► Φεβρουαρίου (64)
- ► Ιανουαρίου (368)
-
►
2020
(4554)
- ► Δεκεμβρίου (400)
- ► Σεπτεμβρίου (381)
- ► Φεβρουαρίου (638)
- ► Ιανουαρίου (691)
-
▼
2019
(4999)
- ► Δεκεμβρίου (924)
-
▼
Σεπτεμβρίου
(845)
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Journal of Cosmetic Dermatology,Early View ...
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Clinical Anatomy
- Journal of Voice
- What causes increased passive stiffness of plant...
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Foraging consistency of coral reef fishes across...
- International Journal of Environmental Research ...
- Incidence and Outcomes of Sepsis in Korea: A Nat...
- Mucinous cystadenoma of oral minor salivary gland...
- Follow-Up of an Implant-Supported Rehabilitation...
- Ebola virus disease: Recent advancs in diagnosti...
- Social determinants of mental health – Let's not...
- Observations of Distortion Product Otoacoustic E...
- A Survey of Current Procurement Travel Practices...
- Intracranial Electroencephalography in Pediatric...
- Effect of diabetes-specific nutrition formulas ...
- Australian Skin Cancer Genetic Study Seeks to R...
- Platelet‐rich plasma improves the therapeutic e...
- Timing of voiding cystourethrography after febri...
- Karpenisi is a town in central Greece. It is the c...
- Complications Associated With the Anesthesia Tra...
- AMEDEO Otorhinolaryngologyhttp://www.amedeo.comht...
- Oncology
- Formulation of survival acceptor medium able to...
- Asthma and the Weather: What's the Link? ...
- Laudation on Professor Roland Laszig Laudation o...
- Inhaltsverzeichnis BYE BYE MADEIRA MIT MUSIK QI-...
- Spinalkanalstenose Hot Topic: Wirbelsäule Die lu...
- Directory: AAO Officers and OrganizationsPublica...
- From the American Academy of Pediatrics, Pedi...
- Adult Traumatic Brachial Plexus InjuriesAdult tr...
- Elizabeth Barrett-Connor, 1935–2019, Talc, Asbes...
- Highlights of the November issue, Bibliometric a...
- Opportunities for Healthy Learning as a Social D...
- Prevalence and Impact on Mechanical Ventilation ...
- Evaluation of Renal Function Disorder With Urina...
- Service based comparison of group cognitive beha...
- No Fellow Left Behind, Graduating Fellows’ Proce...
- Development of a combined CMV-UL97 C592F and CMV...
- Dermatology,Early View Correspondence
- The Risk and Cost of Limited Clinician and Pat...
- Dermatology and Venereology,.Accepted Articles ...
- Has spectral-domain optical coherence tomography...
- Acute epididymo-orchitis due to Salmonella Typhi...
- Waist circumference or sarcopenic obesity; which...
- Oncology
- Otolaryngology–Head and Neck Surgery , ...
- Ear, Nose & Throat Journal ,
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Integrative Cancer Therapies are available onli...
- Clinical OtolaryngologyAccepted Articles Accep...
- JoVE: Journal of Visualized Experiments,
- Letter about outcome differences between recanal...
- Intramedulläre Button-Refixation der distalen Bi...
- Ammoniumbituminosulfonat Panorama Dermatologisch...
- Relating response shift and cognitive appraisal ...
- Allergy & RhinologyEarly View Online Version o...
- Occupational health in Pakistan: challenges and ...
- DermatologyEarly View Online Version of Record...
- DermatologyAccepted Articles Accepted, unedite...
- Clinical and Experimental DermatologyEarly View ...
- Clinical and Experimental DermatologyAccepted Ar...
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Antibiotics, Vol. 8, Pages 167: Comparison o...
- Prevalence of Obstructive Sleep Apnea in Pat...
- Appendectomy in Third Trimester of Pregnancy...
- A patient with conventional and follicular v...
- World Neurosurgery
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου