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Pharmacological Reports : PR Dec 2023Psychedelics are compounds acting by serotonin 5-hydroxytryptamine (5-HT) receptor activation and induce several behavioral responses. They are of special interest... (Review)
Review
Psychedelics are compounds acting by serotonin 5-hydroxytryptamine (5-HT) receptor activation and induce several behavioral responses. They are of special interest because of their positive effects on neuropsychiatric disorders (depression and posttraumatic stress disorder). However, several findings revealed that some psychedelic actions are similar to symptoms observed in schizophrenia (psychosis, sensorimotor gating impairments, attention, and working memory deficits) which might limit their clinical applications. Psychedelics activate some neurotransmitters, i.e., serotonergic, and glutamatergic, that are also impaired in schizophrenia. Therefore, the neurobiological background of psychedelics and schizophrenia is partially similar. Another important aspect to discuss is the perspective of using psychedelics in schizophrenia therapy. Postmortem studies showed a loss of synapses in schizophrenia, and the positive effects of psychedelics on neuroplasticity (synaptogenesis, neurogenesis, and neuritogenesis) might be essential in the context of schizophrenia therapy. However, because of psychedelics' psychotic action, the recommended doses of psychedelics in schizophrenia treatment are not established, and subpsychedelic dosing or microdosing are considered. Exploratory studies are needed to determine the tolerability of treatment and appropriate dosing regimen. Another therapeutic option is using non-hallucinogenic psychedelic analogs that also induce neuroplastic outcomes but do not have psychotogenic effects. Further preclinical and clinical studies are needed to recognize the potential effectiveness of 5-HT agonists in schizophrenia therapy.
Topics: Humans; Hallucinogens; Schizophrenia; Serotonin; Psychotic Disorders; Memory, Short-Term
PubMed: 37899392
DOI: 10.1007/s43440-023-00546-5 -
Smad7 in the hippocampus contributes to memory impairment in aged mice after anesthesia and surgery.Journal of Neuroinflammation Jul 2023Postoperative cognitive dysfunction (POCD) is a common neurological complication following anesthesia and surgery. Increasing evidence has demonstrated that...
BACKGROUND
Postoperative cognitive dysfunction (POCD) is a common neurological complication following anesthesia and surgery. Increasing evidence has demonstrated that neuroinflammation caused by systemic inflammatory responses during the perioperative period is a key factor in the occurrence of POCD. In addition, SMAD family member 7 (Smad7) has been confirmed to play vital roles in the pathogenesis and treatment of inflammatory diseases, such as inflammatory bowel disease. However, whether Smad7 participates in the regulatory process of neuroinflammation and apoptosis in the development of POCD is still unknown.
METHODS
In this study, a POCD mouse model was constructed by unilateral nephrectomy under anesthesia, and cognitive function was assessed using the fear conditioning test and open field test. The expression of Smad7 at the mRNA and protein levels in the hippocampus 3 days after surgery was examined by qRT-PCR, western blot and immunofluorescence assays. Furthermore, to identify whether the elevation of Smad7 in the hippocampus after unilateral nephrectomy contributes to cognitive impairment, the expression of Smad7 in the hippocampal CA1 region was downregulated by crossing Smad7 conditional mutant mice and CaMKIIα-Cre line T29-1 transgenic mice or stereotaxic injection of shRNA-Smad7. Inflammation and apoptosis in the hippocampus were assessed by measuring the mRNA levels of typical inflammatory cytokines, including TNF-α, IL-1β, IL-6, CCL2, CXCL1, and CXCL2, and the protein levels of apoptotic proteins, including Bax and Bcl2. In addition, apoptosis in the hippocampus postoperation was investigated by a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining assay. Finally, western blotting was used to explore how Smad7 mediates inflammation and apoptosis postoperation.
RESULTS
The results unequivocally revealed that elevated Smad7 in the hippocampal CA1 region significantly inhibited TGF-β signal transduction by blocking Smad2/3 phosphorylation, which enhanced neuroinflammation and apoptosis in the hippocampus and further led to learning and memory impairment after surgery.
CONCLUSIONS
Our results revealed that Smad7 contributes to cognitive impairment after surgery by enhancing neuroinflammation and apoptosis in the hippocampus and might serve as a promising therapeutic target for the treatment of memory impairment after anesthesia surgery.
Topics: Animals; Mice; Anesthesia; Cognitive Dysfunction; Hippocampus; Inflammation; Memory Disorders; Mice, Inbred C57BL; Neuroinflammatory Diseases; Postoperative Cognitive Complications; RNA, Messenger; Smad7 Protein
PubMed: 37507781
DOI: 10.1186/s12974-023-02849-z -
Frontiers in Psychology 2023The mathematical study of human memory is still an open challenge. Cognitive psychology and neuroscience have given a big contribution to understand how the human memory... (Review)
Review
The mathematical study of human memory is still an open challenge. Cognitive psychology and neuroscience have given a big contribution to understand how the human memory is structured and works. Cognitive psychologists developed experimental paradigms, conceived quantitative measures of performance in memory tasks for both healthy people and patients with memory disorders, but in terms of mathematical modeling human memory there is still a lot to do. There are many ways to mathematically model human memory, for example, by using mathematical analysis, linear algebra, statistics, and artificial neural networks. The aim of this study is to provide the reader with a description of some prominent models, involving mathematical analysis and linear algebra, designed to describe how memory works by predicting the results of psychological experiments. We have ordered the models from a chronological point of view and, for each model, we have emphasized what are, in our opinion, the strong and weak points. We are aware that this study covers just a part of human memory modeling as well as that we have made a personal selection, which is arguable. Nevertheless, our hope is to help scientists to modeling human memory and its diseases.
PubMed: 38187417
DOI: 10.3389/fpsyg.2023.1298235 -
Cell Reports Jul 2023The neural circuit mechanisms underlying postoperative cognitive dysfunction (POCD) remain elusive. We hypothesized that projections from the medial prefrontal cortex...
The neural circuit mechanisms underlying postoperative cognitive dysfunction (POCD) remain elusive. We hypothesized that projections from the medial prefrontal cortex (mPFC) to the amygdala are involved in POCD. A mouse model of POCD in which isoflurane (1.5%) combined with laparotomy was used. Virally assisted tracing techniques were used to label the relevant pathways. Fear conditioning, immunofluorescence, whole-cell patch-clamp recordings, and chemogenetic and optogenetic techniques were applied to investigate the role of mPFC-amygdala projections in POCD. We find that surgery impairs memory consolidation but not retrieval of consolidated memories. In POCD mice, the glutamatergic pathway from the prelimbic cortex to the basolateral amygdala (PL-BLA) shows reduced activity, whereas the glutamatergic pathway from the infralimbic cortex to the basomedial amygdala (IL-BMA) shows enhanced activity. Our study indicates that the hypoactivity in the PL-BLA pathway interrupts memory consolidation, whereas the hyperactivity in the IL-BMA promotes memory extinction, in POCD mice.
Topics: Mice; Animals; Prefrontal Cortex; Amygdala; Basolateral Nuclear Complex; Cerebral Cortex; Memory Disorders; Neural Pathways
PubMed: 37392387
DOI: 10.1016/j.celrep.2023.112719 -
Neurobiology of Learning and Memory Oct 2023Exposure to acute and chronic stress has significant effects on the basic mechanisms of associative learning and memory. Stress can both impair and enhance associative... (Review)
Review
Exposure to acute and chronic stress has significant effects on the basic mechanisms of associative learning and memory. Stress can both impair and enhance associative learning depending on type, intensity, and persistence of the stressor, the subject's sex, the context that the stress and behavior is experienced in, and the type of associative learning taking place. In some cases, stress can cause or exacerbate the maladaptive behavior that underlies numerous psychiatric conditions including anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, substance use disorder, and others. Therefore, it is critical to understand how the varied effects of stress, which may normally facilitate adaptive behavior, can also become maladaptive and even harmful. In this review, we highlight several findings of associative learning and decision-making processes that are affected by stress in both human and non-human subjects and how they are related to one another. An emerging theme from this work is that stress biases behavior towards less flexible strategies that may reflect a cautious insensitivity to changing contingencies. We consider how this inflexibility has been observed in different associative learning procedures and suggest that a goal for the field should be to clarify how factors such as sex and previous experience influence this inflexibility.
Topics: Humans; Adaptation, Psychological; Anxiety Disorders; Conditioning, Classical; Stress Disorders, Post-Traumatic
PubMed: 37598745
DOI: 10.1016/j.nlm.2023.107812 -
Science Bulletin Oct 2023The persistence of pathological memory is the basis of several psychiatric disorders. Memory retrieval induces "reconsolidation", a time interval during which the... (Review)
Review
The persistence of pathological memory is the basis of several psychiatric disorders. Memory retrieval induces "reconsolidation", a time interval during which the original memory becomes labile and destabilized. Time- and retrieval-dependent processes and memory reconsolidation are critical periods for memory interference. Modulating memory reconsolidation has received considerable research attention as a treatment protocol for several psychiatric conditions such as posttraumatic stress disorder, addiction, anxiety, and trauma-related disorders. This specific time window provides an opportunity for intervention regarding mental diseases. This article reviews the effect of modulating memory reconsolidation using behavioral-, brain stimulation-, and pharmacological-based interventions, which may help bridge the gap between intervention in laboratories and application in clinical practice. The potential advantages, limitations, challenges, and opportunities for memory reconsolidation manipulations were discussed.
Topics: Humans; Extinction, Psychological; Memory; Anxiety Disorders; Stress Disorders, Post-Traumatic; Psychiatry
PubMed: 37689533
DOI: 10.1016/j.scib.2023.08.050 -
Nature Communications Jul 2023Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders,...
Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization of trauma-related memory engrams and generalizes fear responses. Although PTSD may be viewed as a memory-based disorder, no approved treatments target pathological fear memory processing. Hippocampal sharp wave-ripples (SWRs) and concurrent neocortical oscillations are scaffolds to consolidate contextual memory, but their role during fear processing remains poorly understood. Here, we show that closed-loop, SWR triggered neuromodulation of the medial forebrain bundle (MFB) can enhance fear extinction consolidation in male rats. The modified fear memories became resistant to induced recall (i.e., 'renewal' and 'reinstatement') and did not reemerge spontaneously. These effects were mediated by D2 receptor signaling-induced synaptic remodeling in the basolateral amygdala. Our results demonstrate that SWR-triggered closed-loop stimulation of the MFB reward system enhances extinction of fearful memories and reducing fear expression across different contexts and preventing excessive and persistent fear responses. These findings highlight the potential of neuromodulation to augment extinction learning and provide a new avenue to develop treatments for anxiety disorders.
Topics: Rats; Male; Animals; Fear; Extinction, Psychological; Memory; Mental Recall; Basolateral Nuclear Complex; Stress Disorders, Post-Traumatic; Memory Disorders
PubMed: 37407557
DOI: 10.1038/s41467-023-39546-7 -
Acta Neurologica Belgica Aug 2023Since the hippocampus is predominantly susceptible to injuries caused by COVID-19, there are increasing data indicating the likelihood of post-infection memory loss and... (Review)
Review
Since the hippocampus is predominantly susceptible to injuries caused by COVID-19, there are increasing data indicating the likelihood of post-infection memory loss and quickening neurodegenerative disorders, such as Alzheimer's disease. This is due to the fact that the hippocampus has imperative functions in spatial and episodic memory as well as learning. COVID-19 activates microglia in the hippocampus and induces a CNS cytokine storm, leading to loss of hippocampal neurogenesis. The functional and structural changes in the hippocampus of COVID-19 patients can explain neuronal degeneration and reduced neurogenesis in the human hippocampus. This will open a window to explain memory and cognitive dysfunctions in "long COVID" through the resultant loss of hippocampal neurogenesis.
Topics: Humans; COVID-19; Alzheimer Disease; Hippocampus; Learning; Memory Disorders
PubMed: 37226033
DOI: 10.1007/s13760-023-02291-1 -
Pharmacological Research Aug 2023Synaptic dysfunction plays a crucial role in the pathogenesis of Alzheimer's disease (AD). α/β-hydrolase domain-containing 6 (ABHD6) contributes to synaptic...
Synaptic dysfunction plays a crucial role in the pathogenesis of Alzheimer's disease (AD). α/β-hydrolase domain-containing 6 (ABHD6) contributes to synaptic dysfunctions, and ABHD6 inhibition has shown potential therapeutic value in neurological disorders. However, the role of ABHD6 in AD has not been fully defined. In this study, we demonstrated that adeno-associated virus (AAV) mediated shRNA targeting ABHD6 in hippocampal neurons attenuated synaptic dysfunction and memory impairment of APPswe/PS1dE9 (APP/PS1) mice, while it didn't affect the amyloid-beta (Aβ) levels and neuroinflammation in the brains. In addition, intraperitoneal injection of wwl70, a specific inhibitor of ABHD6, improved synaptic plasticity and memory function in APP/PS1 mice, which might attribute to the activation of endogenous cannabinoid signaling. Furthermore, wwl70 significantly decreased the Aβ levels and neuroinflammation in the hippocampus of AD mice, and enhanced Aβ phagocytized by microglia. In conclusion, for the first time our data have shown that ABHD6 inhibition might be a promising strategy for AD treatment, and wwl70 is a potential candidate for AD drug development pipeline.
Topics: Animals; Mice; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Disease Models, Animal; Hydrolases; Memory Disorders; Mice, Transgenic; Monoacylglycerol Lipases; Neuroinflammatory Diseases
PubMed: 37480972
DOI: 10.1016/j.phrs.2023.106864 -
Physiological Research Apr 2024ADHD is a common chronic neurodevelopmental disorder and is characterized by persistent inattention, hyperactivity, impulsivity and are often accompanied by learning and... (Review)
Review
ADHD is a common chronic neurodevelopmental disorder and is characterized by persistent inattention, hyperactivity, impulsivity and are often accompanied by learning and memory impairment. Great evidence has shown that learning and memory impairment of ADHD plays an important role in its executive function deficits, which seriously affects the development of academic, cognitive and daily social skills and will cause a serious burden on families and society. With the increasing attention paid to learning and memory impairment in ADHD, relevant research is gradually increasing. In this article, we will present the current research results of learning and memory impairment in ADHD from the following aspects. Firstly, the animal models of ADHD, which display the core symptoms of ADHD as well as with learning and memory impairment. Secondly, the molecular mechanism of has explored, including some neurotransmitters, receptors, RNAs, etc. Thirdly, the susceptibility gene of ADHD related to the learning and impairment in order to have a more comprehensive understanding of the pathogenesis. Key words: Learning and memory, ADHD, Review.
Topics: Attention Deficit Disorder with Hyperactivity; Humans; Animals; Memory Disorders; Learning; Disease Models, Animal; Learning Disabilities; Memory
PubMed: 38710050
DOI: 10.33549/physiolres.935202