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Arquivos de Neuro-psiquiatria May 2024New hippocampal neurons are continuously generated in the adult human brain. Several studies have demonstrated that the proliferation of hippocampal cells is strongly... (Review)
Review
New hippocampal neurons are continuously generated in the adult human brain. Several studies have demonstrated that the proliferation of hippocampal cells is strongly influenced by a variety of stimuli, including pesticides exposure. These effects are particularly important because neurogenesis dysregulation could be associated with the decline of neuronal and cognitive functions and the possible development of neuropsychiatric disorders.
Topics: Pesticides; Humans; Hippocampus; Neurogenesis; Neurons; Animals
PubMed: 38763143
DOI: 10.1055/s-0044-1786853 -
Scientific Reports May 2024The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite....
The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.
Topics: Humans; Transcranial Direct Current Stimulation; Hypothalamus; Male; Adult; Female; Feasibility Studies; Obesity; Cross-Over Studies; Appetite; Middle Aged; Nerve Net; Appetite Regulation; Reaction Time
PubMed: 38762574
DOI: 10.1038/s41598-024-61852-3 -
Scientific Reports May 2024Childhood maltreatment (CM) is known to influence brain development. To obtain a better understanding of related brain alterations, recent research has focused on the...
Childhood maltreatment (CM) is known to influence brain development. To obtain a better understanding of related brain alterations, recent research has focused on the influence of the type and timing of CM. We aimed to investigate the association between type and timing of CM and local brain volume. Anatomical magnetic resonance images were collected from 93 participants (79 female/14 male) with a history of CM. CM history was assessed with the German Interview Version of the "Maltreatment and Abuse Chronology of Exposure" scale, "KERF-40 + ". Random forest regressions were performed to assess the impact of CM characteristics on the volume of amygdala, hippocampus and anterior cingulate cortex (ACC). The volume of the left ACC was predicted by neglect at age 3 and 4 and abuse at age 16 in a model including both type and timing of CM. For the right ACC, overall CM severity and duration had the greatest impact on volumetric alterations. Our data point to an influence of CM timing on left ACC volume, which was most pronounced in early childhood and in adolescence. We were not able to replicate previously reported effects of maltreatment type and timing on amygdala and hippocampal volume.
Topics: Humans; Female; Male; Child Abuse; Magnetic Resonance Imaging; Child; Adolescent; Brain; Child, Preschool; Hippocampus; Adult; Amygdala; Organ Size; Gyrus Cinguli; Young Adult
PubMed: 38762570
DOI: 10.1038/s41598-024-62051-w -
Scientific Reports May 2024Despite the therapeutic potential of chemogenetics, the method lacks comprehensive preclinical validation, hindering its progression to human clinical trials. We aimed...
Despite the therapeutic potential of chemogenetics, the method lacks comprehensive preclinical validation, hindering its progression to human clinical trials. We aimed to validate a robust but simple in vivo efficacy assay in rats which could support chemogenetic drug discovery by providing a quick, simple and reliable animal model. Key methodological parameters such as adeno-associated virus (AAV) serotype, actuator drug, dose, and application routes were investigated by measuring the food-intake-reducing effect of chemogenetic inhibition of the lateral hypothalamus (LH) by hM4D(Gi) designer receptor stimulation. Subcutaneous deschloroclozapine in rats transfected with AAV9 resulted in a substantial reduction of food-intake, comparable to the efficacy of exenatide. We estimated that the effect of deschloroclozapine lasts 1-3 h post-administration. AAV5, oral administration of deschloroclozapine, and clozapine-N-oxide were also effective but with slightly less potency. The strongest effect on food-intake occurred within the first 30 min after re-feeding, suggesting this as the optimal experimental endpoint. This study demonstrates that general chemogenetic silencing of the LH can be utilized as an optimal, fast and reliable in vivo experimental model for conducting preclinical proof-of-concept studies in order to validate the in vivo effectiveness of novel chemogenetic treatments. We also hypothesize based on our results that universal LH silencing with existing and human translatable genetic neuroengineering techniques might be a viable strategy to affect food intake and influence obesity.
Topics: Animals; Clozapine; Rats; Eating; Hypothalamic Area, Lateral; Dependovirus; Male; Proof of Concept Study; Exenatide; Humans
PubMed: 38762561
DOI: 10.1038/s41598-024-62014-1 -
Scientific Reports May 2024Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of...
Oral administration of coenzyme Q10 ameliorates memory impairment induced by nicotine-ethanol abstinence through restoration of biochemical changes in male rat hippocampal tissues.
Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of neurobiological changes in adolescent brain which makes the individual more susceptible for risk-taking and impulsive behaviors. Alcohol and nicotine are among the most available drugs of abuse in adolescents. Prolonged consumption of nicotine and alcohol leads to drug dependence and withdrawal which induce various dysfunctions such as memory loss. Coenzyme Q10 (CoQ is known to improve learning and memory deficits induced by various pathological conditions such as Diabetes mellitus and Alzheimer's disease. In the present study we investigated whether CoQ treatment ameliorates memory loss following a nicotine-ethanol abstinence. Morris water maze and novel object recognition tests were done in male Wistar rats undergone nicotine-ethanol abstinence and the effect of CoQ10 was assessed on at behavioral and biochemical levels. Results indicated that nicotine-ethanol abstinence induces memory dysfunction which is associated with increased oxidative and inflammatory response, reduced cholinergic and neurotrophic function plus elevated Amyloid-B levels in hippocampi. CoQ treatment prevented memory deficits and biochemical alterations. Interestingly, this ameliorative effect of CoQ was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration. CoQ treatment could effectively improve memory defects induced by nicotine-ethanol consumption through attenuation of oxidative damage, inflammation, amyloid-B level and enhancement of cholinergic and neurotrophic drive. Further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects.
Topics: Animals; Ubiquinone; Male; Nicotine; Hippocampus; Memory Disorders; Rats; Rats, Wistar; Administration, Oral; Ethanol; Alcohol Abstinence; Oxidative Stress; Maze Learning
PubMed: 38762560
DOI: 10.1038/s41598-024-61932-4 -
Epilepsy & Behavior : E&B May 2024In this paper we look at non-pharmaceutical treatments for intractable epilepsy based on neurophysiological methods especially with EEG analysis. In summary, there are a... (Review)
Review
In this paper we look at non-pharmaceutical treatments for intractable epilepsy based on neurophysiological methods especially with EEG analysis. In summary, there are a number of limbic and thalamo-cortical related structures involved in the processing of musical emotion (exposure), including the amygdala (arousal, expression of mood, fear), hippocampus (memory, regulation of HPA axis, stress), parahippocampal gyrus (recognition, memory retrieval), insula (valence), temporal poles (connectivity), ventral striatum (expectation and experience of reward), orbitofrontal cortex (valence) and cingulate cortex (autonomic regulation). One method is to audify (a form of sonification) EEG activity to find music by feedback to entrain abnormal EEG activity. We discuss various methods and our use of X-System (https://www.x-system.co.uk/) which is a computational model of the musical brain capable of predicting the neurophysiological effects of music. It models structures and pathways related to responses to music, including the cochlea, brain stem, auditory and motor cortex, as well as basal ganglia, cerebellum and limbic structures. It can predict autonomic and endocrine activity as well as the substrates of electrical activity to select music which can regularise EEG abnormalities to decrease epileptic activity and seizures, especially in those unresponsive to antiepileptic medication or invasive treatments.
PubMed: 38761451
DOI: 10.1016/j.yebeh.2024.109829 -
Scientific Reports May 20245-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is...
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20-50 Hz) and mid (50-100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.
Topics: Animals; Prefrontal Cortex; Rats; Hippocampus; Wakefulness; Male; Sleep; Electroencephalography; Theta Rhythm; Hallucinogens
PubMed: 38760450
DOI: 10.1038/s41598-024-61474-9 -
Scientific Reports May 2024Several lines of evidence demonstrate that the brain histaminergic system is fundamental for cognitive processes and the expression of memories. Here, we investigated...
Several lines of evidence demonstrate that the brain histaminergic system is fundamental for cognitive processes and the expression of memories. Here, we investigated the effect of acute silencing or activation of histaminergic neurons in the hypothalamic tuberomamillary nucleus (TMN neurons) in vivo in both sexes in an attempt to provide direct and causal evidence of the necessary role of these neurons in recognition memory formation and retrieval. To this end, we compared the performance of mice in two non-aversive and non-rewarded memory tests, the social and object recognition memory tasks, which are known to recruit different brain circuitries. To directly establish the impact of inactivation or activation of TMN neurons, we examined the effect of specific chemogenetic manipulations during the formation (acquisition/consolidation) or retrieval of recognition memories. We consistently found that acute chemogenetic silencing of TMN neurons disrupts the formation or retrieval of both social and object recognition memory in males and females. Conversely, acute chemogenetic activation of TMN neurons during training or retrieval extended social memory in both sexes and object memory in a sex-specific fashion. These results suggest that the formation or retrieval of recognition memory requires the tonic activity of histaminergic neurons and strengthen the concept that boosting the brain histaminergic system can promote the retrieval of apparently lost memories.
Topics: Animals; Female; Male; Neurons; Mice; Recognition, Psychology; Histamine; Mice, Inbred C57BL; Hypothalamic Area, Lateral; Mental Recall
PubMed: 38760416
DOI: 10.1038/s41598-024-61998-0 -
Nature Communications May 2024The dorsolateral prefrontal cortex (dlPFC) is crucial for regulation of emotion that is known to aid prevention of depression. The broader fronto-cingulo-striatal (FCS)...
The dorsolateral prefrontal cortex (dlPFC) is crucial for regulation of emotion that is known to aid prevention of depression. The broader fronto-cingulo-striatal (FCS) network, including cognitive dlPFC and limbic cingulo-striatal regions, has been associated with a negative evaluation bias often seen in depression. The mechanism by which dlPFC regulates the limbic system remains largely unclear. Here we have successfully induced a negative bias in decision-making in female primates performing a conflict decision-making task, by directly microstimulating the subgenual cingulate cortex while simultaneously recording FCS local field potentials (LFPs). The artificially induced negative bias in decision-making was associated with a significant decrease in functional connectivity from cognitive to limbic FCS regions, represented by a reduction in Granger causality in beta-range LFPs from the dlPFC to the other regions. The loss of top-down directional influence from cognitive to limbic regions, we suggest, could underlie negative biases in decision-making as observed in depressive states.
Topics: Animals; Gyrus Cinguli; Decision Making; Female; Corpus Striatum; Macaca mulatta; Dorsolateral Prefrontal Cortex; Prefrontal Cortex; Electric Stimulation; Nerve Net; Neural Pathways
PubMed: 38760337
DOI: 10.1038/s41467-024-48375-1 -
Science Advances May 2024Intellectual disability (ID) affects ~2% of the population and ID-associated genes are enriched for epigenetic factors, including those encoding the largest family of...
Intellectual disability (ID) affects ~2% of the population and ID-associated genes are enriched for epigenetic factors, including those encoding the largest family of histone lysine acetyltransferases (KAT5-KAT8). Among them is , whose mutations cause KAT6A syndrome, with ID as a common clinical feature. However, the underlying molecular mechanism remains unknown. Here, we find that KAT6A deficiency impairs synaptic structure and plasticity in hippocampal CA3, but not in CA1 region, resulting in memory deficits in mice. We further identify a CA3-enriched gene , encoding Wnt activator R-spondin 2, as a key transcriptional target of KAT6A. Deletion of in excitatory neurons impairs memory formation, and restoring RSPO2 expression in CA3 neurons rescues the deficits in Wnt signaling and learning-associated behaviors in mutant mice. Collectively, our results demonstrate that KAT6A-RSPO2-Wnt signaling plays a critical role in regulating hippocampal CA3 synaptic plasticity and cognitive function, providing potential therapeutic targets for KAT6A syndrome and related neurodevelopmental diseases.
Topics: Animals; Wnt Signaling Pathway; Mice; Histone Acetyltransferases; Cognition; CA3 Region, Hippocampal; Thrombospondins; Neuronal Plasticity; Mice, Knockout
PubMed: 38758792
DOI: 10.1126/sciadv.adm9326