المؤلفون: Li N; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China., Teng SW; Departments of Anatomy and Neurobiology and., Zhao L; Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China., Li JR; College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, China., Xu JL; Institution of Traditional Chinese Medicine Innovation Research, Shandong University of Traditional Chinese Medicine, Jinan, 250355 China., Li N; Departments of Anatomy and Neurobiology and., Shuai JC; Departments of Anatomy and Neurobiology and., Chen ZY; Departments of Anatomy and Neurobiology and zheyuchen@sdu.edu.cn.; Institute of Brain Science, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.; Institution of Traditional Chinese Medicine Innovation Research, Shandong University of Traditional Chinese Medicine, Jinan, 250355 China.

المصدر: The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2021 Aug 18; Vol. 41 (33), pp. 6987-7002. Date of Electronic Publication: 2021 Jul 15.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE

مواضيع طبية MeSH: Avoidance Learning/*physiology , Carboxypeptidase H/*physiology , Hippocampus/*physiology , Maze Learning/*physiology , Membrane Glycoproteins/*metabolism , Membrane Proteins/*metabolism , Nerve Tissue Proteins/*physiology , Neurons/*enzymology , Protein-Tyrosine Kinases/*metabolism , Recognition, Psychology/*physiology, Animals ; Biotinylation ; Fear/physiology ; HEK293 Cells ; Humans ; Intravital Microscopy ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/ultrastructure ; Open Field Test ; Protein Transport ; RNA Interference ; RNA, Small Interfering/genetics ; Rats, Sprague-Dawley ; Signal Transduction ; Rats

مستخلص: Activity-dependent insertion of the tropomyosin-related kinase B (TrkB) receptor into the plasma membrane can explain, in part, the preferential effect of brain-derived neurotrophic factor (BDNF) on active neurons and synapses; however, the underlying molecular mechanisms remain obscure. Here, we report a novel function for carboxypeptidase E (CPE) in controlling chemical long-term potentiation stimuli-induced TrkB surface delivery in hippocampal neurons. Total internal reflection fluorescence assays and line plot assays showed that CPE facilitates TrkB transport from dendritic shafts to the plasma membrane. The Box2 domain in the juxtamembrane region of TrkB and the C terminus of CPE are critical for the activity-dependent plasma membrane insertion of TrkB. Moreover, the transactivator of transcription TAT-CPE ^452-466 , which could block the association between CPE and TrkB, significantly inhibited neuronal activity-enhanced BDNF signaling and dendritic spine morphologic plasticity in cultured hippocampal neurons. Microinfusion of TAT-CPE ^452-466 into the dorsal hippocampus of male C57BL/6 mice inhibited the endogenous interaction between TrkB and CPE and diminished fear-conditioning-induced TrkB phosphorylation, which might lead to an impairment in hippocampal memory acquisition and consolidation but not retrieval. These results suggest that CPE modulates activity-induced TrkB surface insertion and hippocampal-dependent memory and sheds light on our understanding of the role of CPE in TrkB-dependent synaptic plasticity and memory modulation. SIGNIFICANCE STATEMENT It is well known that BDNF acts preferentially on active neurons; however, the underlying molecular mechanism is not fully understood. In this study, we found that the cytoplasmic tail of CPE could interact with TrkB and facilitate the neuronal activity-dependent movement of TrkB vesicles to the plasma membrane. Blocking the association between CPE and TrkB decreased fear-conditioning-induced TrkB phosphorylation and led to hippocampal memory deficits. These findings provide novel insights into the role of CPE in TrkB intracellular trafficking as well as in mediating BDNF/TrkB function in synaptic plasticity and hippocampal memory.
(Copyright © 2021 the authors.)

المؤلفون: Zhou H; Department of Anesthesiology, Columbia University Irving Medical Center, New York, NY, USA., Xie Z; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Brambrink AM; Department of Anesthesiology, Columbia University Irving Medical Center, New York, NY, USA., Yang G; Department of Anesthesiology, Columbia University Irving Medical Center, New York, NY, USA. Electronic address: gy2268@cumc.columbia.edu.

المصدر: British journal of anaesthesia [Br J Anaesth] 2021 Jun; Vol. 126 (6), pp. 1141-1156. Date of Electronic Publication: 2021 Feb 26.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 0372541 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1471-6771 (Electronic) Linking ISSN: 00070912 NLM ISO Abbreviation: Br J Anaesth Subsets: MEDLINE

مواضيع طبية MeSH: Anesthetics, Intravenous/*toxicity , Behavior, Animal/*drug effects , Maze Learning/*drug effects , Motor Activity/*drug effects , Motor Cortex/*drug effects , Neurotoxicity Syndromes/*etiology , Propofol/*toxicity, Animals ; Animals, Newborn ; Calcium Signaling/drug effects ; Elevated Plus Maze Test ; Excitatory Amino Acid Agonists/pharmacology ; GABA Antagonists/pharmacology ; Interneurons/drug effects ; Interneurons/metabolism ; Mice, Transgenic ; Motor Cortex/metabolism ; Motor Cortex/physiopathology ; Neural Inhibition/drug effects ; Neurotoxicity Syndromes/physiopathology ; Neurotoxicity Syndromes/prevention & control ; Neurotoxicity Syndromes/psychology ; Open Field Test/drug effects ; Pyramidal Cells/drug effects ; Pyramidal Cells/metabolism ; Social Behavior

مستخلص: Background: Both animal and retrospective human studies have linked extended and repeated general anaesthesia during early development with cognitive and behavioural deficits later in life. However, the neuronal circuit mechanisms underlying this anaesthesia-induced behavioural impairment are poorly understood.
Methods: Neonatal mice were administered one or three doses of propofol, a commonly used i.v. general anaesthetic, over Postnatal days 7-11. Control mice received Intralipid® vehicle injections. At 4 months of age, the mice were subjected to a series of behavioural tests, including motor learning. During the process of motor learning, calcium activity of pyramidal neurones and three classes of inhibitory interneurones in the primary motor cortex were examined in vivo using two-photon microscopy.
Results: Repeated, but not a single, exposure of neonatal mice to propofol i.p. caused motor learning impairment in adulthood, which was accompanied by a reduction of pyramidal neurone number and activity in the motor cortex. The activity of local inhibitory interneurone networks was also altered: somatostatin-expressing and parvalbumin-expressing interneurones were hypoactive, whereas vasoactive intestinal peptide-expressing interneurones were hyperactive when the mice were performing a motor learning task. Administration of low-dose pentylenetetrazol to attenuate γ-aminobutyric acid A receptor-mediated inhibition or CX546 to potentiate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-subtype glutamate receptor function during emergence from anaesthesia ameliorated neuronal dysfunction in the cortex and prevented long-term behavioural deficits.
Conclusions: Repeated exposure of neonatal mice to propofol anaesthesia during early development causes cortical circuit dysfunction and behavioural impairments in later life. Potentiation of neuronal activity during recovery from anaesthesia reduces these adverse effects of early-life anaesthesia.
(Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

المؤلفون: Xie B; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Zhang Y; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Qi H; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Yao H; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Shang Y; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Yuan S; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Zhang J; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

المصدر: Aging [Aging (Albany NY)] 2020 Nov 10; Vol. 12 (23), pp. 23739-23760. Date of Electronic Publication: 2020 Nov 10.

نوع المنشور: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE

مواضيع طبية MeSH: Behavior, Animal* , Light* , Maze Learning*, Anxiety/*etiology , Learning Disabilities/*etiology , Sepsis/*complications, Age Factors ; Animals ; Anxiety/microbiology ; Anxiety/physiopathology ; Anxiety/psychology ; Disease Models, Animal ; Dysbiosis ; Feces/microbiology ; Gastrointestinal Microbiome ; Intestines/microbiology ; Learning Disabilities/microbiology ; Learning Disabilities/physiopathology ; Learning Disabilities/psychology ; Male ; Mice, Inbred C57BL ; Open Field Test ; Sepsis/microbiology ; Sepsis/physiopathology ; Splenomegaly/etiology ; Splenomegaly/physiopathology ; Vagus Nerve/physiopathology

مستخلص: Light exerts critical non-visual effects on a multitude of physiological processes and behaviors, including sleep-wake behavior and cognitive function. In this study, we investigated the effects of continued exposure to different colors of light on cognitive function after sepsis in old mice. We found that exposure to red light, but not green light, exaggerated learning impairments and anxiety-like behaviors after sepsis. Red light also induced remarkable splenomegaly and altered the diversity and composition of the fecal microbiota. Pseudo germ-free mice transplanted with fecal bacteria from septic mice exposed to red light developed the same behavioral defects and splenomegaly as their donors. Intriguingly, splenectomy and subdiaphragmatic vagotomy reversed the learning impairments and anxiety-like behaviors resulting from red light exposure after sepsis. After subdiaphragmatic vagotomy, no differences in behavior or spleen size were observed among pseudo germ-free mice transplanted with fecal bacteria from septic mice exposed to different colors of light. Our results suggested that red light exposure after sepsis in old mice causes gut microbiota dysfunction, thus stimulating signaling through the subdiaphragmatic vagus nerve that induces splenomegaly and aggravates learning impairments and anxiety-like behaviors.

المؤلفون: Yoshizaki K; Department of Disease Model, Institute for Developmental Research, Aichi Developmental Disability Center, Aichi 480-0392, Japan., Asai M; Department of Disease Model, Institute for Developmental Research, Aichi Developmental Disability Center, Aichi 480-0392, Japan., Hara T; Laboratory of Food and Life Science, Faculty of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan.

المصدر: Nutrients [Nutrients] 2020 Jul 09; Vol. 12 (7). Date of Electronic Publication: 2020 Jul 09.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

مواضيع طبية MeSH: Anxiety* , Diet, High-Fat* , Maze Learning* , Memory, Short-Term*, Anhedonia ; Animals ; Behavior, Animal ; Cognition ; Elevated Plus Maze Test ; Male ; Mice, Inbred C57BL ; Motor Activity ; Open Field Test ; Weight Gain

مستخلص: Obesity is characterized by massive adipose tissue accumulation and is associated with psychiatric disorders and cognitive impairment in human and animal models. However, it is unclear whether high-fat diet (HFD)-induced obesity presents a risk of psychiatric disorders and cognitive impairment. To examine this question, we conducted systematic behavioral analyses in C57BL/6J mice (male, 8-week-old) fed an HFD for 7 weeks. C57BL/6J mice fed an HFD showed significantly increased body weight, hyperlocomotion in the open-field test (OFT) and Y-maze test (YMZT), and impaired sucrose preference in the sucrose consumption test, compared to mice fed a normal diet. Neither body weight nor body weight gain was associated with any of the behavioral traits we examined. Working memory, as assessed by the YMZT, and anxiety-like behavior, as assessed by the elevated plus maze test (EPMT), were significantly correlated with mice fed an HFD, although these behavioral traits did not affect the entire group. These results suggest that HFD-induced obesity does not induce neuropsychiatric symptoms in C57BL/6J mice. Rather, HFD improved working memory in C57BL/6J mice with less anxiety, indicating that an HFD might be beneficial under limited conditions. Correlation analysis of individual traits is a useful tool to determine those conditions.

المؤلفون: Hillman KL; Department of Psychology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand., Wall HJ; Department of Psychology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand., Matthews LO; Department of Psychology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand., Gowing EK; Department of Anatomy, Brain Health Research Centre and Brain Research New Zealand, University of Otago, PO Box 56, Dunedin, 9054, New Zealand., Clarkson AN; Department of Anatomy, Brain Health Research Centre and Brain Research New Zealand, University of Otago, PO Box 56, Dunedin, 9054, New Zealand. andrew.clarkson@otago.ac.nz.

المصدر: Neuromolecular medicine [Neuromolecular Med] 2019 Dec; Vol. 21 (4), pp. 401-413. Date of Electronic Publication: 2019 Jul 16.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Humana Press Country of Publication: United States NLM ID: 101135365 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1174 (Electronic) Linking ISSN: 15351084 NLM ISO Abbreviation: Neuromolecular Med Subsets: MEDLINE

مواضيع طبية MeSH: Hippocampus/*physiopathology , Maze Learning/*physiology , Memory Disorders/*etiology , Prefrontal Cortex/*physiopathology , Stroke/*complications, Animals ; Beta Rhythm ; Electrodes, Implanted ; Exploratory Behavior/physiology ; Male ; Memory Disorders/physiopathology ; Mice ; Mice, Inbred C57BL ; Neural Pathways/physiopathology ; Open Field Test/physiology ; Random Allocation ; Recognition, Psychology/physiology ; Stroke/pathology ; Stroke/physiopathology ; Stroke/psychology ; Theta Rhythm

مستخلص: Frontal infarcts can produce cognitive impairments that affect an individual's ability to function in everyday life. However, the precise types of deficits, and their underlying mechanisms, are not well-understood. Here we used a prefrontal photothrombotic stroke model in C57BL/6J mice to characterise specific cognitive changes that occur in the 6 weeks post-stroke. Behavioural experiments were paired with in vivo electrophysiology to assess whether changes in oscillatory communication between the prefrontal cortex (PFC) and the hippocampus (HPC) mirrored any observed behavioural changes. We found that mice in the stroke group exhibited a delayed onset impairment in tasks of spatial working memory (object location recognition and Y-maze) and that this correlated with reduced PFC-HPC theta band coherence (5-12 Hz) during the task. In the open field, mice in the stroke group exhibited hyperactivity as compared to controls, and stroke animals also exhibited significantly higher beta band activity (13-30 Hz) in the PFC and the HPC. Taken together our results suggest that infarcts in the PFC result in PFC-HPC oscillatory communication changes in the theta and beta bands, correlating with altered performance in spatial memory and open field tasks respectively. Of particular interest, early open field changes in PFC beta band power post-stroke correlated to later-stage spatial memory impairments, highlighting this as a potential biomarker for detecting when spatial memory impairments are likely to occur.

المؤلفون: Haigh, Jessica L, Adhikari, Anna, Copping, Nycole A, Stradleigh, Tyler, Wade, A Ayanna, Catta-Preta, Rinaldo, Su-Feher, Linda, Zdilar, Iva, Morse, Sarah, Fenton, Timothy A, Nguyen, Anh, Quintero, Diana, Agezew, Samrawit, Sramek, Michael, Kreun, Ellie J, Carter, Jasmine, Gompers, Andrea, Lambert, Jason T, Canales, Cesar P, Pennacchio, Len A, Visel, Axel, Dickel, Diane E, Silverman, Jill L, Nord, Alex S

المصدر: Genome Medicine. 13(1)

مصطلحات موضوعية: Biological Sciences, Genetics, Neurosciences, Neurodegenerative, Human Genome, Behavioral and Social Science, Epilepsy, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Good Health and Well Being, Animals, Attention, Base Sequence, Brain, Chromatin, Conserved Sequence, Disease Models, Animal, Electroencephalography, Evolution, Molecular, Female, Gene Expression Regulation, HEK293 Cells, Heterozygote, Homozygote, Humans, Male, Maze Learning, Memory Disorders, Mice, Inbred C57BL, NAV1.1 Voltage-Gated Sodium Channel, Neurons, Open Field Test, Phenotype, Protein Binding, Regulatory Sequences, Nucleic Acid, Sequence Deletion, Survival Analysis, Temperature, Trans-Activators, Mice, Clinical Sciences

الوصف: BackgroundGenes with multiple co-active promoters appear common in brain, yet little is known about functional requirements for these potentially redundant genomic regulatory elements. SCN1A, which encodes the NaV1.1 sodium channel alpha subunit, is one such gene with two co-active promoters. Mutations in SCN1A are associated with epilepsy, including Dravet syndrome (DS). The majority of DS patients harbor coding mutations causing SCN1A haploinsufficiency; however, putative causal non-coding promoter mutations have been identified.MethodsTo determine the functional role of one of these potentially redundant Scn1a promoters, we focused on the non-coding Scn1a 1b regulatory region, previously described as a non-canonical alternative transcriptional start site. We generated a transgenic mouse line with deletion of the extended evolutionarily conserved 1b non-coding interval and characterized changes in gene and protein expression, and assessed seizure activity and alterations in behavior.ResultsMice harboring a deletion of the 1b non-coding interval exhibited surprisingly severe reductions of Scn1a and NaV1.1 expression throughout the brain. This was accompanied by electroencephalographic and thermal-evoked seizures, and behavioral deficits.ConclusionsThis work contributes to functional dissection of the regulatory wiring of a major epilepsy risk gene, SCN1A. We identified the 1b region as a critical disease-relevant regulatory element and provide evidence that non-canonical and seemingly redundant promoters can have essential function.

وصف الملف: application/pdf

URL الوصول: https://escholarship.org/uc/item/6ck6m0x4

المؤلفون: Justel N; Laboratorio de Psicología Experimental y Aplicada (PSEA), Instituto de Investigaciones Médicas (IDIM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires (UBA), Argentina., Salguero A; Instituto de Investigación Médica M. y M. Ferreyra (INIMEC), CONICET Universidad Nacional de Córdoba (UNC), Argentina., Marengo L; Instituto de Investigación Médica M. y M. Ferreyra (INIMEC), CONICET Universidad Nacional de Córdoba (UNC), Argentina., Psyrdellis M; Laboratorio de Psicología Experimental y Aplicada (PSEA), Instituto de Investigaciones Médicas (IDIM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires (UBA), Argentina., Pautassi RM; Instituto de Investigación Médica M. y M. Ferreyra (INIMEC), CONICET Universidad Nacional de Córdoba (UNC), Argentina; Facultad de Psicología, Universidad Nacional de Córdoba (UNC), Argentina. Electronic address: rpautassi@gmail.com.

المصدر: Neuroscience letters [Neurosci Lett] 2021 Jul 13; Vol. 757, pp. 135997. Date of Electronic Publication: 2021 May 28.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Elsevier Scientific Publishers Ireland Country of Publication: Ireland NLM ID: 7600130 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7972 (Electronic) Linking ISSN: 03043940 NLM ISO Abbreviation: Neurosci Lett Subsets: MEDLINE

مواضيع طبية MeSH: Maze Learning/*physiology , Recognition, Psychology/*physiology , Spatial Memory/*physiology, Animals ; Male ; Maze Learning/drug effects ; Models, Animal ; Rats ; Rats, Wistar ; Recognition, Psychology/drug effects ; Scopolamine/administration & dosage ; Spatial Memory/drug effects

مستخلص: Novelty seems to reduce the persistence of aversive memories and to modulate frustration responses, yet much less is known on how this treatment affects memories lacking hedonic or emotional content. The present study analyzed how a 5-min exposure to a novel open field modulated the expression of a spatial recognition memory. Experiment 1 indicated that male Wistar rats trained in a T-maze in which one goal arm is blocked exhibit, when tested 2 h later, preference for the novel arm. This recognition memory was impaired by the muscarinic cholinergic antagonist scopolamine. Postraining, but not pretraining, novelty exposure rescued the cognitive impairment induced by scopolamine (Experiment 2 and 3). Pretraining open field exposure alleviated the lack of memory expression, induced by imposing a 6 h delay between training and testing (Experiment 4). The study shows that a very brief exposure to novelty can improve expression of a spatial, recognition memory, a modulation that - in the case of the pretraining novelty exposure -- emerges even in spite of cholinergic blockade. The present results are consistent with research suggesting that novelty exposure can be an effective, non-pharmacological, treatment to modulate memory expression.
(Copyright © 2021 Elsevier B.V. All rights reserved.)

المؤلفون: Gogokhia N; School of Natural Sciences and Medicine, Ilia State University. 3/5 K/Cholokashvili Avenue, 0162 Tbilisi, Georgia., Japaridze N; Department of Brain Ultrastructure and Nanoarchitecture, Ivane Beritashvili Center of Experimental Biomedicine, 14 Gotua Street, 9160 Tbilisi, Georgia; Medical School, New Vision University, 1A Evgeni Mikeladze Street, 0159 Tbilisi, Georgia., Tizabi Y; Department of Pharmacology, Howard University College of Medicine, Washington, DC, USA., Pataraya L; Department of Brain Ultrastructure and Nanoarchitecture, Ivane Beritashvili Center of Experimental Biomedicine, 14 Gotua Street, 9160 Tbilisi, Georgia., Zhvania MG; School of Natural Sciences and Medicine, Ilia State University. 3/5 K/Cholokashvili Avenue, 0162 Tbilisi, Georgia; Department of Brain Ultrastructure and Nanoarchitecture, Ivane Beritashvili Center of Experimental Biomedicine, 14 Gotua Street, 9160 Tbilisi, Georgia. Electronic address: mzia_zhvania@iliauni.edu.ge.

المصدر: Neuroscience letters [Neurosci Lett] 2021 Jan 18; Vol. 742, pp. 135543. Date of Electronic Publication: 2020 Dec 02.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Elsevier Scientific Publishers Ireland Country of Publication: Ireland NLM ID: 7600130 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7972 (Electronic) Linking ISSN: 03043940 NLM ISO Abbreviation: Neurosci Lett Subsets: MEDLINE

مواضيع طبية MeSH: Sex Characteristics*, Anxiety/*psychology , Exploratory Behavior/*physiology , Maze Learning/*physiology , Motor Activity/*physiology , Noise/*adverse effects, Acoustic Stimulation/adverse effects ; Acoustic Stimulation/methods ; Animals ; Anxiety/etiology ; Female ; Male ; Rats ; Rats, Wistar

مستخلص: Prolong exposure to high intensity white noise (HIWN), defined as a heterogeneous mixture of sound waves extending over a wide frequency range, has detrimental peripheral and central consequences including cardiovascular and emotional effects. Anxiety is a common manifestation of HIWN. Although gender-dependent differences in manifestation of anxiety and/or response to treatment of this condition has been amply documented, potential differences in response to HIWN, a common exposure in combat, construction and rave disco, has not been adequately investigated. In this study, both male and female Wistar rats were subjected to HIWN for 10 consecutive days, 1 h/day. On day 11, a day after the last exposure, the performance of the rats in open field (OF) and elevated plus maze (EPM) was evaluated. Male rats showed a higher anxiety-like response to HIWN as evidenced by: lower number of entries into the open arm of the EPM, lower number of entries into central zone of OF, excess grooming in OF and more boluses in closed arm of EPM. These results indicate that gender-related differences in anxiety in general, and in response to HIWN, in particular, has to be taken into consideration when investigating the neurobiological components and/or treatment modalities.
(Copyright © 2020. Published by Elsevier B.V.)

المؤلفون: Gudasheva TA; Federal State Budgetary Institution 'Zakusov Research Institute of Pharmacology' (FSBI 'Zakusov Institute of Pharmacology'), Baltiyskaya, 8, 125315 Moscow, Russia., Deeva OA; Federal State Budgetary Institution 'Zakusov Research Institute of Pharmacology' (FSBI 'Zakusov Institute of Pharmacology'), Baltiyskaya, 8, 125315 Moscow, Russia., Pantileev AS; Federal State Budgetary Institution 'Zakusov Research Institute of Pharmacology' (FSBI 'Zakusov Institute of Pharmacology'), Baltiyskaya, 8, 125315 Moscow, Russia., Mokrov GV; Federal State Budgetary Institution 'Zakusov Research Institute of Pharmacology' (FSBI 'Zakusov Institute of Pharmacology'), Baltiyskaya, 8, 125315 Moscow, Russia., Rybina IV; Federal State Budgetary Institution 'Zakusov Research Institute of Pharmacology' (FSBI 'Zakusov Institute of Pharmacology'), Baltiyskaya, 8, 125315 Moscow, Russia., Yarkova MA; Federal State Budgetary Institution 'Zakusov Research Institute of Pharmacology' (FSBI 'Zakusov Institute of Pharmacology'), Baltiyskaya, 8, 125315 Moscow, Russia., Seredenin SB; Federal State Budgetary Institution 'Zakusov Research Institute of Pharmacology' (FSBI 'Zakusov Institute of Pharmacology'), Baltiyskaya, 8, 125315 Moscow, Russia.

المصدر: Molecules (Basel, Switzerland) [Molecules] 2020 Nov 04; Vol. 25 (21). Date of Electronic Publication: 2020 Nov 04.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

مواضيع طبية MeSH: Anti-Anxiety Agents*/chemical synthesis , Anti-Anxiety Agents*/chemistry , Anti-Anxiety Agents*/pharmacology , Dipeptides*/chemical synthesis , Dipeptides*/chemistry , Dipeptides*/pharmacology, Maze Learning/*drug effects , Receptors, GABA/*metabolism, Animals ; Ligands ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Structure-Activity Relationship

مستخلص: The translocator protein (TSPO, 18 kDa) plays an important role in the synthesis of neurosteroids by promoting the transport of cholesterol from the outer to the inner mitochondrial membrane, which is the rate-limiting step in neurosteroidogenesis. Stimulation of TSPO by appropriate ligands increases the level of neurosteroids. The present study describes the design, synthesis and investigation of anxiolytic-like effects of a series of N -acyl-tryptophanyl-containing dipeptides. These novel dipeptide TSPO ligands were designed with the original drug-based peptide design strategy using alpidem as non-peptide prototype. The anxiolytic activities were investigated in Balb/C mice using the illuminated open-field and elevated plus-maze tests in outbred laboratory mice ICR (CD-1). Dipeptide GD-102 ( N -phenylpropionyl-l-tryptophanyl-l-leucine amide) in the dose range of 0.01-0.5 mg/kg intraperitoneally (i.p.) has a pronounced anxiolytic activity. The anxiolytic effect of GD-102 was abolished by PK11195, a specific TSPO antagonist. The structure-activity relationship study made it possible to identify a pharmacophore fragment for the dipeptide TSPO ligand. It was shown that l,d-diastereomer of GD-102 has no activity, and the d,l-isomer has less pronounced activity. The anxiolytic activity also disappears by replacing the C-amide group with the methyl ester, a free carboxyl group or methylamide. Consecutive replacement of each amino acid residue with glycine showed the importance of each of the amino acid residues in the structure of the ligand. The most active and technologically available compound GD-102, was selected for evaluation as a potential anxiolytic drug.

المؤلفون: McElroy DL; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., Roebuck AJ; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., Onofrychuk TJ; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., Sandini TM; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., Greba Q; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., Howland JG; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada. Electronic address: john.howland@usask.ca.

المصدر: Neuroscience letters [Neurosci Lett] 2020 Apr 01; Vol. 723, pp. 134839. Date of Electronic Publication: 2020 Feb 14.

نوع المنشور: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Elsevier Scientific Publishers Ireland Country of Publication: Ireland NLM ID: 7600130 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7972 (Electronic) Linking ISSN: 03043940 NLM ISO Abbreviation: Neurosci Lett Subsets: MEDLINE

مواضيع طبية MeSH: Technology Transfer*, Fitness Trackers/*trends , Locomotion/*physiology , Maze Learning/*physiology , Software/*trends, Animals ; Male ; Rats ; Rats, Long-Evans

مستخلص: Animal tracking software is an important tool to record and analyze locomotor activity during behavioral assays that provides considerable advantages over traditional manual scoring approaches (e.g., counting line crosses on a grid overlay or using a stopwatch to score time spent in regions of interest). Although several options are available to researchers, tracking software is often costly or requires advanced technical knowledge to operate efficiently. In this study, a free open-source behavioral tracking pipeline called ezTrack was compared to commercially available software for assessing rat locomotor behavior and time spent in regions of interest during elevated plus maze (EPM) and open field test (OFT) assays. ezTrack produced nearly identical results to the commercial software. Overall, these results suggest that ezTrack is a cost-effective approach to quantify some aspects of behavior in these tasks.
Competing Interests: Declaration of Competing Interest No conflicts of interests are declared by the authors.
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