212,623 results match your criteria neurons pharmacological

Toll-like receptor 4 signaling is critical for the adaptive cellular stress response effects induced by intermittent fasting in the mouse brain.

Neuroscience 2021 May 3. Epub 2021 May 3.

Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo 05508-900, Brazil. Electronic address:

Among different kinds of dietary energy restriction, intermittent fasting (IF) has been considered a dietary regimen which causes a mild stress to the organism. IF can stimulate proteins and signaling pathways related to cell stress that can culminate in the increase of the body resistance to severe stress conditions. Energy intake reduction induced by IF can induce modulation of receptors, kinases, and phosphatases, which in turn can modulate the activation of transcription factors such as NF-E2-related factor 2 (NRF2) and cAMP response element-binding (CREB) which regulate the transcription of genes related to the translation of proteins such as growth factors: brain-derived neurotrophic factor (BDNF), chaperone proteins: heat shock proteins (HSP), and so on. Read More

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Locus revealed: Painlessness via loss of Na1.7 at central terminals of sensory neurons.

Neuron 2021 May;109(9):1413-1416

Pharmacology Institute, Medical Faculty Heidelberg, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany. Electronic address:

How genetic loss of the sodium channel Na1.7 results in painlessness is puzzling. MacDonald et al. Read More

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Pseudomonas aeruginosa-induced nociceptor activation increases susceptibility to infection.

PLoS Pathog 2021 May 6;17(5):e1009557. Epub 2021 May 6.

Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

We report a rapid reduction in blink reflexes during in vivo ocular Pseudomonas aeruginosa infection, which is commonly attributed and indicative of functional neuronal damage. Sensory neurons derived in vitro from trigeminal ganglia (TG) were able to directly respond to P. aeruginosa but reacted significantly less to strains of P. Read More

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Inhibition of hyperactivity of the dorsal raphe 5-HTergic neurons ameliorates hippocampal seizure.

CNS Neurosci Ther 2021 May 6. Epub 2021 May 6.

Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.

Aims: Epilepsy, frequently comorbid with depression, easily develops drug resistance. Here, we investigated how dorsal raphe (DR) and its 5-HTergic neurons are implicated in epilepsy.

Methods: In mouse hippocampal kindling model, using immunochemistry, calcium fiber photometry, and optogenetics, we investigated the causal role of DR 5-HTergic neurons in seizure of temporal lobe epilepsy (TLE). Read More

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Calcium-permeable AMPA receptor activity and GluA1 trafficking in the basolateral amygdala regulate operant alcohol self-administration.

Addict Biol 2021 May 5:e13049. Epub 2021 May 5.

Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Addiction is viewed as maladaptive glutamate-mediated neuroplasticity that is regulated, in part, by calcium-permeable AMPA receptor (CP-AMPAR) activity. However, the contribution of CP-AMPARs to alcohol-seeking behavior remains to be elucidated. We evaluated CP-AMPAR activity in the basolateral amygdala (BLA) as a potential target of alcohol that also regulates alcohol self-administration in C57BL/6J mice. Read More

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Noninvasive Ultrasound Stimulation of Ventral Tegmental Area Induces Reanimation from General Anaesthesia in Mice.

Research (Wash D C) 2021 12;2021:2674692. Epub 2021 Apr 12.

Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, Shenzhen, China 518055.

Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness (DOC). However, these treatments require invasive procedures. This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice. Read More

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Neuroinflammatory Mechanisms of Mitochondrial Dysfunction and Neurodegeneration in Glaucoma.

Joao N Duarte

J Ophthalmol 2021 15;2021:4581909. Epub 2021 Apr 15.

Neuroinflammation Unit, Biotech Research & Innovation Center, University of Copenhagen, Copenhagen, Denmark.

The exact mechanism of retinal ganglion cell loss in the pathogenesis of glaucoma is yet to be understood. Mitochondrial damage-associated molecular patterns (DAMPs) resulting from mitochondrial dysfunction have been linked to Leber's hereditary optic neuropathy and autosomal dominant optic atrophy, as well as to brain neurodegenerative diseases. Recent evidence shows that, in conditions where mitochondria are damaged, a sustained inflammatory response and downstream pathological inflammation may ensue. Read More

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Tanshinone IIA Protects Against Cerebral Ischemia Reperfusion Injury by Regulating Microglial Activation and Polarization NF-κB Pathway.

Front Pharmacol 2021 19;12:641848. Epub 2021 Apr 19.

Department of Pharmacy, Punan Hospital, Pudong New District, Shanghai, China.

Tanshinone IIA, a fat-soluble diterpenoid isolated from Salvia miltiorrhiza Bunge, has been shown to attenuate the cerebral ischemic injury. The aim of this study was to examine the effects on neuroprotection and microglia activation of Tanshinone IIA. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Read More

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Fast odour dynamics are encoded in the olfactory system and guide behaviour.

Nature 2021 May 5. Epub 2021 May 5.

Sensory Circuits and Neurotechnology Laboratory, The Francis Crick Institute, London, UK.

Odours are transported in turbulent plumes, which result in rapid concentration fluctuations that contain rich information about the olfactory scenery, such as the composition and location of an odour source. However, it is unclear whether the mammalian olfactory system can use the underlying temporal structure to extract information about the environment. Here we show that ten-millisecond odour pulse patterns produce distinct responses in olfactory receptor neurons. Read More

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Nicotine Enhances Firing Activity of Layer 5 Pyramidal Neurons in the Medial Prefrontal Cortex through Inhibition of Kv7 Channels.

Biol Pharm Bull 2021 ;44(5):724-731

Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University.

Nicotine enhances attention, working memory and recognition. One of the brain regions associated with these effects of nicotine is the medial prefrontal cortex (mPFC). However, cellular mechanisms that induce the enhancing effects of nicotine remain unclear. Read More

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January 2021

Dysregulation of the mesoprefrontal dopamine circuit mediates an early-life stress-induced synaptic imbalance in the prefrontal cortex.

Cell Rep 2021 May;35(5):109074

Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Max Planck Institute of Neurobiology, Martinsried 82152, Germany. Electronic address:

Stress adversely affects an array of cognitive functions. Although stress-related disorders are often addressed in adulthood, far less is known about how early-life stress (ELS) affects the developing brain in early postnatal periods. Here we show that ELS, induced by maternal separation, leads to synaptic alteration of layer 2/3 pyramidal neurons in the prefrontal cortex (PFC) of mice. Read More

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Gain of PITRM1 peptidase in cortical neurons affords protection of mitochondrial and synaptic function in an advanced age mouse model of Alzheimer's disease.

Aging Cell 2021 May 5:e13368. Epub 2021 May 5.

Department of Surgery, Columbia University, New York, NY, USA.

Mitochondrial dysfunction is one of the early pathological features of Alzheimer's disease (AD). Accumulation of cerebral and mitochondrial Aβ links to mitochondrial and synaptic toxicity. We have previously demonstrated the mechanism by which presequence peptidase (PITRM1)-mediated clearance of mitochondrial Aβ contributes to mitochondrial and cerebral amyloid pathology and mitochondrial and synaptic stress in adult transgenic AD mice overexpressing Aβ up to 12 months old. Read More

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Rapid nucleus-scale reorganization of chromatin in neurons enables transcriptional adaptation for memory consolidation.

PLoS One 2021 5;16(5):e0244038. Epub 2021 May 5.

Institute of Physiology, Focus Program Translational Neurosciences, University Medical Center, Johannes-Gutenberg University, Mainz, Germany.

The interphase nucleus is functionally organized in active and repressed territories defining the transcriptional status of the cell. However, it remains poorly understood how the nuclear architecture of neurons adapts in response to behaviorally relevant stimuli that trigger fast alterations in gene expression patterns. Imaging of fluorescently tagged nucleosomes revealed that pharmacological manipulation of neuronal activity in vitro and auditory cued fear conditioning in vivo induce nucleus-scale restructuring of chromatin within minutes. Read More

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A honokiol-enriched Magnolia officinalis Rehder & E.H. Wilson. bark extract possesses anxiolytic-like activity with neuroprotective effect through the modulation of CB1 receptor.

J Pharm Pharmacol 2021 May 5. Epub 2021 May 5.

Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology, University of Florence, Florence, Italy.

Objectives: The exposure of neurons to an excessive excitatory stimulation induces the alteration of the normal neuronal function. Mood disorders are among the first signs of alterations in the central nervous system function. Magnolia officinalis bark extract has been extensively used in the traditional medicine systems of several countries, showing several pharmacological activities. Read More

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Serotonin 5-HT7 receptors require cyclin-dependent kinase 5 to rescue hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome.

Eur J Neurosci 2021 May 5. Epub 2021 May 5.

Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.

Fragile X Syndrome is a genetic form of intellectual disability associated with autism, epilepsy and mood disorders. Electrophysiology studies in Fmr1 knockout (KO) mice, a murine model of Fragile X Syndrome, have demonstrated alterations of synaptic plasticity, with exaggerated long-term depression induced by activation of metabotropic glutamate receptors (mGluR-LTD) in Fmr1 KO hippocampus. We have previously demonstrated that activation of serotonin 5-HT7 receptors reverses mGluR-LTD in the hippocampus of wild-type and Fmr1 KO mice, thus correcting a synaptic dysfunction typically observed in this disease model. Read More

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Central Acting Hsp10 Regulates Mitochondrial Function, Fatty Acid Metabolism, and Insulin Sensitivity in the Hypothalamus.

Antioxidants (Basel) 2021 Apr 30;10(5). Epub 2021 Apr 30.

Junior Research Group Central Regulation of Metabolism, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.

Mitochondria are critical for hypothalamic function and regulators of metabolism. Hypothalamic mitochondrial dysfunction with decreased mitochondrial chaperone expression is present in type 2 diabetes (T2D). Recently, we demonstrated that a dysregulated mitochondrial stress response (MSR) with reduced chaperone expression in the hypothalamus is an early event in obesity development due to insufficient insulin signaling. Read More

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The Role of the Excitation:Inhibition Functional Balance in the mPFC in the Onset of Antidepressants.

Neuropharmacology 2021 May 1:108573. Epub 2021 May 1.

Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China; Beijing Institute of Basic Medical Sciences, Beijing, China. Electronic address:

Currently available antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), generally require weeks to months to produce a therapeutic response, but the mechanism of action underlying the delayed onset of antidepressant-like action remains to be elucidated. The balance between excitatory glutamatergic pyramidal neurons and inhibitory γ-aminobutyric acid (GABA) interneurons, i.e. Read More

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The challenging diversity of neurons in the ventral tegmental area: a commentary of Miranda-Barrientos, J. et al., Eur J Neurosci 2021.

Eur J Neurosci 2021 May 4. Epub 2021 May 4.

Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Department of Neurosciences, Faculty of Medicine, Université de Montréal, CNS Research Group (GRSNC), Montréal, QC, Canada, H3C 3J7.

In 1992, a landmark paper by Johnson and North published in the Journal of Physiology and entitled "Two types of neurone in the rat ventral tegmental area and their synaptic inputs" (Johnson & North, 1992) provided a first glimpse of the diversity of neurons in this part of the brain. The ventral tegmental (VTA) area was initially better known for the presence of dopamine (DA)-containing neurons projecting to the ventral striatum and for its key role in motivated behaviors and drug addiction. Read More

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FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model.

NPJ Aging Mech Dis 2021 May 3;7(1). Epub 2021 May 3.

Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA.

Abnormal accumulation of hyperphosphorylated tau induces pathogenesis in neurodegenerative diseases, like Alzheimer's disease. Molecular chaperones with peptidyl-prolyl cis/trans isomerase (PPIase) activity are known to regulate these processes. Previously, in vitro studies have shown that the 52 kDa FK506-binding protein (FKBP52) interacts with tau inducing its oligomerization and fibril formation to promote toxicity. Read More

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Autophagy in axonal and presynaptic development.

Curr Opin Neurobiol 2021 Apr 30;69:139-148. Epub 2021 Apr 30.

Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, 98199, USA; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA; Department of Pharmacology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address:

The study of autophagy in the nervous system has predominantly centered on degeneration. Evidence is now cementing crucial roles for autophagy in neuronal development and growth, especially in axonal and presynaptic compartments. A picture is emerging that autophagy typically promotes the growth of axons and reduces presynaptic stability. Read More

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Phosphorylated tau targeted small-molecule PROTACs for the treatment of Alzheimer's disease and Tauopathies.

Biochim Biophys Acta Mol Basis Dis 2021 Apr 30:166162. Epub 2021 Apr 30.

Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Public Health, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Speech, Language, and Hearing Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. Electronic address:

Tau is a microtubule-stabilizing protein that plays an important role in the formation of axonal microtubules in neurons. Phosphorylated tau (p-Tau) has received great attention in the field of Alzheimer's disease (AD) as a potential therapeutic target due to its involvement with synaptic damage and neuronal dysfunction. Mounting evidence suggests that amyloid beta (Aβ)-targeted clinical trials continuously failed; therefore, it is important to consider alternative therapeutic strategies such as p-tau-PROTACs targeted small molecules for AD and other tauopathies. Read More

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Cerebral Dopamine Neurotrophic Factor Reduces α-Synuclein Aggregation and Propagation and Alleviates Behavioural Alterations in vivo.

Mol Ther 2021 Apr 30. Epub 2021 Apr 30.

Institute of Biotechnology, HiLIFE, University of Helsinki, FI-00014, Helsinki, Finland; Neuroscience Center, HiLIFE, University of Helsinki, FI-00014, Helsinki, Finland. Electronic address:

A molecular hallmark in Parkinson's Disease (PD) pathogenesis are α-synuclein aggregates. Cerebral dopamine neurotrophic factor (CDNF) is an atypical growth factor that is mostly resident in the endoplasmic reticulum but exerts its effects both intracellularly and extracellularly. One of the beneficial effects of CDNF can be protecting neurons from the toxic effects of α-synuclein. Read More

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Acteoside exerts neuroprotection effects in the model of Parkinson's disease via inducing autophagy: Network pharmacology and experimental study.

Eur J Pharmacol 2021 Apr 30:174136. Epub 2021 Apr 30.

State Key Laboratory of Pathogenesis, Prevention and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. Electronic address:

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. At present, the incidence rate of PD is increasing worldwide, there is no effective cure available so far, and currently using drugs are still limited in efficacy due to serious side effects. Acteoside (ACT) is an active ingredient of many valuable medicinal plants, possesses potential therapeutic effects on many pathological conditions. Read More

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cGMP signalling in dorsal root ganglia and the spinal cord: Various functions in development and adulthood.

Br J Pharmacol 2021 May 3. Epub 2021 May 3.

Institute of Pharmacology and Clinical Pharmacy, Goethe University, Frankfurt am Main, Germany.

Cyclic GMP (cGMP) is a second messenger that regulates numerous physiological and pathophysiological processes. In recent years, more and more studies have uncovered multiple roles of cGMP signalling pathways in the somatosensory system. Accumulating evidence suggests that cGMP regulates different cellular processes from embryonic development through adulthood. Read More

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Characterization of Ca-Sensing Receptor-Mediated Ca Influx in Microvascular bEND.3 Endothelial Cells.

Chin J Physiol 2021 Mar-Apr;64(2):80-87

Department of Physiology, China Medical University, Taichung, Taiwan.

Ca-sensing receptors (CaSR), activated by elevated concentrations of extracellular Ca, have been known to regulate functions of thyroid cells, neurons, and endothelial cells (EC). In this report, we studied CaSR-mediated Ca influx in mouse cerebral microvascular EC (bEND.3 cells). Read More

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Melanocortin 4 receptor signals at the neuronal primary cilium to control food intake and body weight.

J Clin Invest 2021 May;131(9)

Department of Medicine and The Diabetes Center and.

The melanocortin 4 receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis, and mutations in the MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R-expressing neurons are unknown. We recently reported that the MC4R localizes to the primary cilium, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether the MC4R functions in this organelle. Read More

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Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration.

iScience 2021 Apr 29;24(4):102376. Epub 2021 Mar 29.

Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

The group of retinal degenerations, retinitis pigmentosa (RP), comprises more than 150 genetic abnormalities affecting photoreceptors. Finding degenerative pathways common to all genetic abnormalities may allow general treatment such as neuroprotection. Neuroprotection may include enhancing the function of cells that directly support photoreceptors, retinal pigment epithelial cells, and Müller glia. Read More

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Resilience to anhedonia-passive coping induced by early life experience is linked to a long-lasting reduction of I current in VTA dopaminergic neurons.

Neurobiol Stress 2021 May 15;14:100324. Epub 2021 Apr 15.

Dept. of Psychology and Center "Daniel Bovet", Sapienza University, Rome, Italy.

Exposure to aversive events during sensitive developmental periods can affect the preferential coping strategy adopted by individuals later in life, leading to either stress-related psychiatric disorders, including depression, or to well-adaptation to future adversity and sources of stress, a behavior phenotype termed "resilience". We have previously shown that interfering with the development of mother-pups bond with the Repeated Cross Fostering (RCF) stress protocol can induce resilience to depression-like phenotype in adult C57BL/6J female mice. Here, we used patch-clamp recording in midbrain slice combined with both and pharmacology to test our hypothesis of a link between electrophysiological modifications of dopaminergic neurons in the intermediate Ventral Tegmental Area (VTA) of RCF animals and behavioral resilience. Read More

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The Promise of the Zebrafish Model for Parkinson's Disease: Today's Science and Tomorrow's Treatment.

Front Genet 2021 15;12:655550. Epub 2021 Apr 15.

Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University Malaysia (IIUM), Kuantan, Malaysia.

The second most prevalent neurodegenerative disorder in the elderly is Parkinson's disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more evidence is required concerning its pathogenesis. Read More

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Agitation and Dementia: Prevention and Treatment Strategies in Acute and Chronic Conditions.

Front Neurol 2021 16;12:644317. Epub 2021 Apr 16.

Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy.

Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes. Read More

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