Activity-dependent diffusion trapping of AMPA receptors as a key step for expression of early LTP.

This review focuses on the activity-dependent diffusion trapping of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as a crucial mechanism for the expression of early long-term potentiation (LTP), a process central to learning and memory. Despite decades of research, the precise mechanisms by which LTP induction leads to an increase in AMPAR responses at synapses have been elusive. We review the different hypotheses that have been put forward to explain the increased AMPAR responsiveness during LTP. We discuss the dynamic nature of AMPAR complexes, including their constant turnover and activity-dependent modifications that affect their synaptic accumulation. We highlight a hypothesis suggesting that AMPARs are diffusively trapped at synapses through activity-dependent interactions with protein-based binding slots in the post-synaptic density (PSD), offering a potential explanation for the increased synaptic strength during LTP. Furthermore, we outline the challenges still to be addressed before we fully understand the functional roles and molecular mechanisms of AMPAR dynamic nanoscale organization in LTP. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Phosphorylation of PSD-95 at serine 73 in dCA1 is required for extinction of contextual fear.

The updating of contextual memories is essential for survival in a changing environment. Accumulating data indicate that the dorsal CA1 area (dCA1) contributes to this process. However, the cellular and molecular mechanisms of contextual fear memory updating remain poorly understood. Postsynaptic density protein 95 (PSD-95) regulates the structure and function of glutamatergic synapses. Here, using dCA1-targeted genetic manipulations in vivo, combined with ex vivo 3D electron microscopy and electrophysiology, we identify a novel, synaptic mechanism that is induced during attenuation of contextual fear memories and involves phosphorylation of PSD-95 at Serine 73 in dCA1. Our data provide the proof that PSD-95-dependent synaptic plasticity in dCA1 is required for updating of contextual fear memory.

Disrupting interaction between miR-132 and Mmp9 3'UTR improves synaptic plasticity and memory in mice.

As microRNAs have emerged to be important regulators of molecular events occurring at the synapses, the new questions about their regulatory effect on the behavior have araised. In the present study, we show for the first time that the dysregulated specific targeting of miR132 to Mmp9 mRNA in the mouse brain results in the increased level of Mmp9 protein, which affects synaptic plasticity and has an effect on memory formation. Our data points at the importance of complex and precise regulation of the Mmp9 level by miR132 in the brain.

High-resolution imaging and manipulation of endogenous AMPA receptor surface mobility during synaptic plasticity and learning.

Regulation of synaptic neurotransmitter receptor content is a fundamental mechanism for tuning synaptic efficacy during experience-dependent plasticity and behavioral adaptation. However, experimental approaches to track and modify receptor movements in integrated experimental systems are limited. Exploiting AMPA-type glutamate receptors (AMPARs) as a model, we generated a knock-in mouse expressing the biotin acceptor peptide (AP) tag on the GluA2 extracellular N-terminal. Cell-specific introduction of biotin ligase allows the use of monovalent or tetravalent avidin variants to respectively monitor or manipulate the surface mobility of endogenous AMPAR containing biotinylated AP-GluA2 in neuronal subsets. AMPAR immobilization precluded the expression of long-term potentiation and formation of contextual fear memory, allowing target-specific control of the expression of synaptic plasticity and animal behavior. The AP tag knock-in model offers unprecedented access to resolve and control the spatiotemporal dynamics of endogenous receptors, and opens new avenues to study the molecular mechanisms of synaptic plasticity and learning.

PSD-95 Serine 73 phosphorylation is not required for induction of NMDA-LTD.

PSD-95 is a major scaffolding protein of the post-synaptic density (PSD) of a glutamatergic synapse. PSD-95, via interactions with stargazin, anchors AMPA receptors at the synapse and regulates AMPAR currents. The expression of PSD-95 is regulated during synaptic plasticity. It is, however, unknown whether this regulation is required for induction of functional plasticity of glutamatergic synapses. Here, we show that NMDA-induced long-term depression of synaptic transmission (NMDA-LTD) is accompanied by downregulation of PSD-95 protein levels. Using pharmacologic and molecular manipulations, we further demonstrate that the NMDA-induced downregulation of PSD-95 depends on the activation of CaMKII and CaMKII-driven phosphorylation of PSD-95 serine 73. Surprisingly, neither CaMKII activity nor CaMKII-dependent phosphorylation of PSD-95 serine 73 are required for the expression of NMDA-LTD. These results support the hypothesis that synaptic plasticity of AMPARs may occur without dynamic regulation of PSD-95 protein levels.

Ketamine applications beyond anesthesia - A literature review.

Ketamine's clinical use began in the 1970s. Physicians benefited from its safety and ability to induce short-term anesthesia and analgesia. The psychodysleptic effects caused by the drug called its further clinical use into question. Despite these unpleasant effects, ketamine is still applied in veterinary medicine, field medicine, and specialist anesthesia. Recent intensive research brought into light new possible applications of this drug. It began to be used in acute, chronic and cancer pain management. Most interesting reports come from research on the antidepressive and antisuicidal properties of ketamine giving hope for the creation of an effective treatment for major depressive disorder. Other reports highlight the possible use of ketamine in treating addiction, asthma and preventing cancer growth. Besides clinical use, the drug is also applied to in animal model of schizophrenia. It seems that nowadays, with numerous possible applications, the use of ketamine has returned; to its former glory. Nevertheless, the drug must be used with caution because still the mechanisms by which it executes its functions and long-term effects of its use are not fully known. This review aims to discuss the well-known and new promising applications of ketamine.

Neurodevelopmental phenotype caused by a de novo PTPN4 single nucleotide variant disrupting protein localization in neuronal dendritic spines.

Protein tyrosine phosphatase non-receptor type 4 (PTPN4) encodes non-receptor protein tyrosine phosphatase implicated in synaptic plasticity and innate immune response. The only report of PTPN4-associated disease described a neurodevelopmental disorder associated with a whole gene deletion. We describe a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems with a novel mosaic de novo variant in PTPN4 (hg19 chr2:g.120620188 T > C, NM_002830.3:p.[Leu72Ser]/c.215T>C) located in domain that controls protein subcellular distribution. Studies in mouse hippocampal neurons transfected with non-mutated or mutated human PTPN4 showed that despite their similar expression in neurons the mutated protein was absent from dendritic spines. Next, we studied patient's primary blood mononuclear cells' response to lipopolysaccharide stimulation and found no difference from control in phosphorylation of TBK1 and IRF3 (involved in Toll-like receptor 4 signaling) and induction of cytokines' messenger RNA. We conclude that the PTPN4 p.(Leu72Ser) variant is a likely cause of neurodevelopmental symptoms of our proband whereas its role in immune dysfunction requires further studies.

[Quality of life and depressive symptoms in patients diagnosed with uterus cancer]. / Jakosc zycia i depresyjnosc u pacjentek z rozpoznaniem raka trzonu macicy.

UNLABELLED: In the present study quality of life and depressive symptoms as well as the influence of illness on emotional state in patients with diagnosis of uterus cancer was evaluated. The aim of the study was to evaluate quality of life and depressive symptoms in women diagnosed with uterus cancer who underwent surgical treatment and complementary therapy. MATERIAL AND METHODS: The study has been conducted on randomly chosen group of 100 patients diagnosed with uterus cancer who underwent surgical treatment and adjunctive therapy. Surveys has been conducted 6 months after completed therapy when no recurrence of carcinomatous disease was confirmed. Quality of life was evaluated using quality of life questionnaire EORTC QLQ-C30 and depressive symptoms were measured by means of Beck's depression self-rating scale. RESULTS: In the conducted study in most cases patients with diagnosis of uterus cancer didn't show symptoms of depression and in 40% of patients there were mild symptoms of depressive disorder. The results show that patients without depressive symptoms had better quality of life compared to those with concomitant depressive symptoms and it was statistically significant. CONCLUSIONS: Patients with diagnosed uterus cancer in whom no symptoms of depression were detected presented with better quality of life compared to patients with depressive symptoms. Emotional state of patients with uterus cancer can be an important factor influencing their quality of life.

[Quality of life and depressiveness of women patients diagnosed with ovarian cancer treated with surgery and after previous adjuvant therapy]. / Jakosc zycia i depresyjnosc u pacjentek z rozpoznaniem raka jajnika leczonych operacyjnie oraz po przebytej terapii uzupelniajacej.

UNLABELLED: In the present study undertaken to assess the quality of life and depression of women patients diagnosed with ovarian cancer. The aim of the study was to assess quality of life and severity of depression of women diagnosed with ovarian cancer treated with surgery, and then underwent adjuvant radio or chemotherapy treatment. MATERIAL AND METHODS: The principle of study was to included on random selection 42 women diagnosed with ovarian cancer who were treated surgically, and then subjected to adjuvant therapy. Quality of life was based on patient self-assessment using the EORTC QLQ C-30 form. The severity of depression was assessed by the Beck Depression Scale. RESULTS: Our results showed that in the vast majority the quality of life of women with ovarian cancer who develop depression, evaluate their own quality of life at a low level. In contrast patients who did not get depressed in most cases evaluated their own quality of life at the average level. In studies it has been shown that patients manifesting symptoms of depression compared to women not having these symptoms differ in a statistically significant way, in terms of quality of life. CONCLUSIONS: The results indicate that women diagnosed with ovarian cancer who have demonstrated the co-existence of depression presented a lower quality of life. The study indicates that in the majority of cases the severity of depression of patients diagnosed with ovarian cancer were mild.

[Selected problems in the forensic-psychiatric evaluation of persons posing a likelihood of repeating a criminal act]. / Wybrane problemy w opiniowaniu sadowo-psychiatrycznym osób stwarzajacych prawdopodobienstwo ponownego popelnienia czynu przestepczego.

In the current penal code, compared to previous regulations, there have been alterations concerning medical security measures. These amendments have been prompted by socio-politic circumstances in Poland as well as implementation of Mental Health Act. According to the current law the court, on the request of expert psychiatrists, can pronounce a sentence of obligatory stay in psychiatric institution for perpetrator of criminal act who has been deemed not sane due to 31 subsection 1 of penal code and who is predictably able of recidivism. In legal-medical practice those less experienced expert psychiatrists may encounter difficulties producing expertise for the court, especially evaluating probability of recurrence of committing a criminal act and resulting request for psychiatric detention. In order to make this issue more acquainted we present a review of literature concerning it.

[Evaluation of risk factors coexistence for suicidal behavior with features of bipolarity in patients with depressive disorders]. / Ocena wspólwystepowania czynników ryzyka zachowan samobójczych z cechami dwubiegunowosci u chorych z zaburzeniami depresyjnymi.

UNLABELLED: Suicide being a deliberate act of depriving one-self of life is a complex phenomenon, which occurs as a result of the interaction between biological, genetic, psychological, sociological and environmental factors. More and more studies have provided evidence that subthreshold states of BP II (bipolar disorder type II) may increase the risk of suicidal behavior. The aim of the present study was to evaluate relationship of suicidal behavior and bipolarity features according to MDQ (Mood Disorder Questionnaire) and HCL-32 (Hypomania Check List-32) questionnaires in recurrent depressive disorder. MATERIAL AND METHODS: The study covered 61 subjects with diagnosis of recurrent depression. HDRS (Hamilton Depression Rating Scale), MDQ and HCL-32 rating scales have been employed. Self-developed questionnaires concerning social and personal history as well as risk factors for suicidal behavior have also been used. RESULTS: In the case of majority of suicidal risk factors no statistically significant coexistence with bipolarity according to MDQ as well as HCL-32 questionnaires was observed. Only such suicide risk factors as making one's last will, psychoactive substances abuse and family history of suicide were statistically more frequent in depressive patients with bipolarity features according to MDQ compared to those depressives without bipolarity. CONCLUSIONS: The results of present study doesn't allow to prove the usefulness of MDQ and HCL-32 questionnaires in rating suicide risk.

[Influence of parity on the body mass of neonates]. / Wplyw dzietnosci matki na mase urodzeniowa noworodka.

OBJECTIVES: The purpose of the study was to determine whether there exists a positive correlation between the mother's parity and the child's weight on delivery. MATERIALS AND METHODS: A retrospective study has been conducted on a selected group of 86 multiriparas with three deliveries. Only in term babies of healthy mothers were taken into consideration. Data derived from cases has been analyzed by means of Microsoft Excel and Statistica 6.0 software. RESULTS: In 65.1% of the cases, the birth weight of the second neonate exceeded the weight of the first one. The rate diminishes to 51.2% when we compare the third child with the second. In 2.3% of the records no changes have been observed. The abovementioned criteria enabled us to form three groups out of the initial cohort and perform further analysis. CONCLUSIONS: Significant correlation between birth weight of the first and second newborn has been found. No such correlation was found in the case of the second compared to the third delivery.