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Nature Communications Jun 2024In vertebrates, folliculogenesis and ovulation are regulated by two distinct pituitary gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH)....
In vertebrates, folliculogenesis and ovulation are regulated by two distinct pituitary gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Currently, there is an intriguing consensus that a single hypothalamic neurohormone, gonadotropin-releasing hormone (GnRH), regulates the secretion of both FSH and LH, although the required timing and functions of FSH and LH are different. However, recent studies in many non-mammalian vertebrates indicated that GnRH is dispensable for FSH function. Here, by using medaka as a model teleost, we successfully identify cholecystokinin as the other gonadotropin regulator, FSH-releasing hormone (FSH-RH). Our histological and in vitro analyses demonstrate that hypothalamic cholecystokinin-expressing neurons directly affect FSH cells through the cholecystokinin receptor, Cck2rb, thereby increasing the expression and release of FSH. Remarkably, the knockout of this pathway minimizes FSH expression and results in a failure of folliculogenesis. Here, we propose the existence of the "dual GnRH model" in vertebrates that utilize both FSH-RH and LH-RH.
Topics: Animals; Gonadotropin-Releasing Hormone; Follicle Stimulating Hormone; Female; Oryzias; Hypothalamus; Neurons; Luteinizing Hormone; Ovarian Follicle; Ovulation
PubMed: 38937445
DOI: 10.1038/s41467-024-49564-8 -
In Vivo (Athens, Greece) 2024Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them...
BACKGROUND/AIM
Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known.
MATERIALS AND METHODS
In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot.
RESULTS
The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses.
CONCLUSION
Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them.
Topics: Animals; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Mice; Depression; Disease Models, Animal; Non-alcoholic Fatty Liver Disease; Male; Mice, Inbred C57BL; Corticotropin-Releasing Hormone; Diet, High-Fat; Adrenocorticotropic Hormone; Liver; Fatty Liver; Corticosterone
PubMed: 38936893
DOI: 10.21873/invivo.13618 -
Journal of Clinical Neurophysiology :... Jul 2024Stereoelectroencephalography (SEEG) has emerged as a transformative tool in epilepsy surgery, shedding light on the complex network dynamics involved in focal epilepsy.... (Review)
Review
Stereoelectroencephalography (SEEG) has emerged as a transformative tool in epilepsy surgery, shedding light on the complex network dynamics involved in focal epilepsy. This review explores the role of SEEG in elucidating the role of deep brain structures, namely the basal ganglia and thalamus, in epilepsy. SEEG advances understanding of their contribution to seizure generation, propagation, and control by permitting precise and minimally invasive sampling of these brain regions. The basal ganglia, comprising the subthalamic nucleus, globus pallidus, substantia nigra, and striatum, have gained recognition for their involvement in both focal and generalized epilepsy. Electrophysiological recordings reveal hyperexcitability and increased synchrony within these structures, reinforcing their role as critical nodes within the epileptic network. Furthermore, low-frequency and high-frequency stimulation of the basal ganglia have demonstrated potential in modulating epileptogenic networks. Concurrently, the thalamus, a key relay center, has garnered prominence in epilepsy research. Disrupted thalamocortical connectivity in focal epilepsy underscores its significance in seizure maintenance. The thalamic subnuclei, including the anterior nucleus, centromedian, and medial pulvinar, present promising neuromodulatory targets, suggesting pathways for personalized epilepsy therapies. The prospect of multithalamic SEEG and thalamic SEEG stimulation trials has the potential to revolutionize epilepsy management, offering tailored solutions for challenging cases. SEEG's ability to unveil the dynamics of deep brain structures in epilepsy promises enhanced and personalized epilepsy care in our new era of precision medicine. Until deep brain SEEG is accepted as a standard of care, a rigorous informed consent process remains paramount for patients for whom such an exploration is proposed.
Topics: Humans; Basal Ganglia; Electroencephalography; Thalamus; Epilepsy; Stereotaxic Techniques; Deep Brain Stimulation
PubMed: 38935656
DOI: 10.1097/WNP.0000000000001097 -
Journal of Behavioral Addictions Jun 2024Changes in brain structural connections appear to be important in the pathophysiology of substance use disorders, but their role in behavioral addictions, such as...
BACKGROUND
Changes in brain structural connections appear to be important in the pathophysiology of substance use disorders, but their role in behavioral addictions, such as gambling disorder (GD), is unclear. GD also offers a model to study addiction mechanisms without pharmacological confounding factors. Here, we used multimodal MRI data to examine the integrity of white matter connections in individuals with GD. We hypothesized that the affected areas would be in the fronto-striatal-thalamic circuit.
METHODS
Twenty individuals with GD (mean age: 64 years, GD duration: 15.7 years) and 40 age- and sex-matched healthy controls (HCs) underwent detailed clinical examinations together with brain 3T MRI scans (T1, T2, FLAIR and DWI). White matter (WM) analysis involved fractional anisotropy and lesion load, while gray matter (GM) analysis included voxel- and surface-based morphometry. These measures were compared between groups, and correlations with GD-related behavioral characteristics were examined.
RESULTS
Individuals with GD showed reduced WM integrity in the left and right frontal parts of the corona radiata and corpus callosum (pFWE < 0.05). WM gambling symptom severity (SOGS score) was negatively associated to WM integrity in these areas within the left hemisphere (p < 0.05). Individuals with GD also exhibited higher WM lesion load in the left anterior corona radiata (pFWE < 0.05). GM volume in the left thalamus and GM thickness in the left orbitofrontal cortex were reduced in the GD group (pFWE < 0.05).
CONCLUSIONS
Similar to substance addictions, the fronto-striatal-thalamic circuit is also affected in GD, suggesting that this circuitry may have a crucial role in addictions, independent of pharmacological substances.
Topics: Humans; Male; Middle Aged; Gray Matter; White Matter; Gambling; Female; Magnetic Resonance Imaging; Aged; Multimodal Imaging; Frontal Lobe; Thalamus
PubMed: 38935433
DOI: 10.1556/2006.2024.00031 -
Behavioral Neuroscience Jun 2024In recent years, there have been significant advances in our understanding of the positive symptoms of schizophrenia, such as hallucinations and delusions. This progress... (Review)
Review
In recent years, there have been significant advances in our understanding of the positive symptoms of schizophrenia, such as hallucinations and delusions. This progress has been significantly aided by the use of associative learning-based approaches in human subjects and preclinical animal models. Here, we first review experimental research focusing on the abnormal processing of absent stimuli using three different conditioning phenomena: conditioned hallucinations, mediated conditioning, and trace conditioning. We then review studies investigating the ability to reduce focal processing of physically present but informationally redundant stimuli using habituation, latent inhibition, and blocking. The results of these different lines of research are then summarized within the framework of Wagner's (1981) standard operating procedures model, an associative learning model with explicit reference to the internal representations of both present and absent stimuli. Within this framework, the central deficit associated with positive symptoms can be described as a failure to suppress the focal processing of both absent stimuli and present but irrelevant stimuli. This can explain the wide range of results obtained in different experimental settings. Finally, we briefly discuss the role of the hippocampus and its interaction with dopaminergic transmission in the emergence of such abnormal stimulus representations and learning. Overall, we hope that the theoretical framework and empirical findings offered by the associative learning approach will continue to facilitate and integrate analyses of schizophrenia conducted at the psychological and behavioral levels on the one hand, and at the neural and molecular levels on the other, by serving as a useful interface between them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Topics: Humans; Association Learning; Schizophrenia; Animals; Psychotic Disorders; Hallucinations; Schizophrenic Psychology; Conditioning, Classical; Hippocampus; Perception
PubMed: 38934921
DOI: 10.1037/bne0000599 -
Behavioral Neuroscience Jun 2024A growing body of literature indicates that mediated learning techniques have specific utility for tapping into reality testing in animal models of neuropsychiatric...
A growing body of literature indicates that mediated learning techniques have specific utility for tapping into reality testing in animal models of neuropsychiatric illness. In particular, recent work has shown that animal models that recapitulate various endophenotypes of schizophrenia are particularly vulnerable to impairments in reality testing when undergoing mediated learning. Multiple studies have indicated that these effects are dopamine receptor 2-dependent and correlated with aberrant insular cortex (IC) activity. However, until now, the connection between dopamine and the IC had not been investigated. Here, we utilized a novel intersectional approach to label mesencephalic dopamine cells that specifically project to the insular cortex in both wild-type controls and transgenic mice expressing the dominant-negative form of the Disrupted-in-Schizophrenia-1 (DISC-1) gene. Using these techniques, we identified a population of cells that project from the ventral tegmental area (VTA) to the IC. Afterward, we conducted multiple studies to test the necessity of this circuit in behaviors ranging from gustatory detection to the maintenance of effort and, finally, mediated performance. Our results indicate that perturbations of the DISC-1 genetic locus lead to a reduction in the number of cells in the VTA → IC circuit. Behaviorally, VTA → IC circuitry does not influence gustatory detection or motivation to acquire sucrose reward; however, inactivation of this circuit differentially suppresses Pavlovian approach behavior in wild-type and DISC-1 transgenic mice during mediated performance testing. Moreover, under these testing conditions, inactivation of this circuit predisposes wild-type (but not DISC-1) mice to display impaired reality testing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Topics: Animals; Mice, Transgenic; Dopaminergic Neurons; Mice; Insular Cortex; Male; Ventral Tegmental Area; Mice, Inbred C57BL; Neural Pathways; Reward; Disease Models, Animal; Dopamine; Nerve Tissue Proteins; Mesencephalon; Schizophrenia
PubMed: 38934920
DOI: 10.1037/bne0000580 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that...
In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that obesogenic high-fat and sugar diet intake during adolescence (adoHFSD) impairs hippocampus (HPC)-dependent memory in rodents. These results were obtained in males only and it remains to evaluate whether adoHFSD has similar effect in females. Therefore, here, we investigated the effects of adoHFSD consumption on HPC-dependent contextual fear memory and associated brain activation in male and female mice. Exposure to adoHFSD increased fat mass accumulation and glucose levels in both males and females but impaired contextual fear memory only in males. Compared with females, contextual fear conditioning induced higher neuronal activation in the dorsal and ventral HPC (CA1 and CA3 subfields) as well as in the medial prefrontal cortex in males. Also, adoHFSD-fed males showed enhanced c-Fos expression in the dorsal HPC, particularly in the dentate gyrus, and in the basolateral amygdala compared with the other groups. Finally, chemogenetic inactivation of the dorsal HPC rescued adoHFSD-induced memory deficits in males. Our results suggest that males are more vulnerable to the effects of adoHFSD on HPC-dependent aversive memory than females, due to overactivation of the dorsal HPC.
Topics: Animals; Fear; Male; Female; Hippocampus; Diet, High-Fat; Obesity; Sex Characteristics; Mice; Memory; Mice, Inbred C57BL; Prefrontal Cortex
PubMed: 38934712
DOI: 10.1093/cercor/bhae254 -
Frontiers in Neural Circuits 2024Various mammals have shown that sensory stimulation plays a crucial role in regulating the development of diverse structures, such as the olfactory bulb (OB), cerebral... (Review)
Review
Various mammals have shown that sensory stimulation plays a crucial role in regulating the development of diverse structures, such as the olfactory bulb (OB), cerebral cortex, hippocampus, and retina. In the OB, the dendritic development of excitatory projection neurons like mitral/tufted cells is influenced by olfactory experiences. Odor stimulation is also essential for the dendritic development of inhibitory OB interneurons, such as granule and periglomerular cells, which are continuously produced in the ventricular-subventricular zone throughout life. Based on the morphological and molecular features, OB interneurons are classified into several subtypes. The role for each interneuron subtype in the control of olfactory behavior remains poorly understood due to lack of each specific marker. Among the several OB interneuron subtypes, a specific granule cell subtype, which expresses the oncofetal trophoblast glycoprotein (Tpbg or 5T4) gene, has been reported to be required for odor detection and discrimination behavior. This review will primarily focus on elucidating the contribution of different granule cell subtypes, including the Tpbg/5T4 subtype, to olfactory processing and behavior during the embryonic and adult stages.
Topics: Animals; Interneurons; Olfactory Bulb; Humans; Neurogenesis
PubMed: 38933598
DOI: 10.3389/fncir.2024.1427378 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Jun 2024Motor imagery is often used in the fields of sports training and neurorehabilitation for its advantages of being highly targeted, easy to learn, and requiring no special...
[A study on the effects of transcranial direct current stimulation combined with motor imagery on brain function based on electroencephalogram and near infrared spectrum].
Motor imagery is often used in the fields of sports training and neurorehabilitation for its advantages of being highly targeted, easy to learn, and requiring no special equipment, and has become a major research paradigm in cognitive neuroscience. Transcranial direct current stimulation (tDCS), an emerging neuromodulation technique, modulates cortical excitability, which in turn affects functions such as locomotion. However, it is unclear whether tDCS has a positive effect on motor imagery task states. In this paper, 16 young healthy subjects were included, and the electroencephalogram (EEG) signals and near-infrared spectrum (NIRS) signals of the subjects were collected when they were performing motor imagery tasks before and after receiving tDCS, and the changes in multiscale sample entropy (MSE) and haemoglobin concentration were calculated and analyzed during the different tasks. The results found that MSE of task-related brain regions increased, oxygenated haemoglobin concentration increased, and total haemoglobin concentration rose after tDCS stimulation, indicating that tDCS increased the activation of task-related brain regions and had a positive effect on motor imagery. This study may provide some reference value for the clinical study of tDCS combined with motor imagery.
Topics: Humans; Transcranial Direct Current Stimulation; Electroencephalography; Spectroscopy, Near-Infrared; Brain; Imagination; Motor Cortex; Hemoglobins; Young Adult
PubMed: 38932533
DOI: 10.7507/1001-5515.202310029 -
Clinical and Translational Science Jun 2024Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of...
Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1 miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology. The prefrontal lobe, anterior cingulate, and hippocampus from NF1 and wild-type miniswine were examined longitudinally, revealing abnormalities in mature oligodendrocytes and astrocytes, and microglial activation over time. Imbalances in GABA: Glutamate ratios and GAD67 expression were observed in the hippocampus and motor cortex, supporting the role of disruption in inhibitory neurotransmission in NF1 cognitive impairment and motor dysfunction. Moreover, NF1 miniswine demonstrated slower and shorter steps, indicative of a balance-preserving response commonly observed in NF1 patients, and progressive memory and learning impairments. Collectively, our findings affirm the effectiveness of NF1 miniswine as a valuable resource for assessing cognitive and motor impairments associated with NF1, investigating the involvement of specific neural circuits and glia in these processes, and evaluating potential therapeutic interventions.
Topics: Animals; Neurofibromatosis 1; Disease Models, Animal; Mice; Neurofibromin 1; Behavior, Animal; Male; Hippocampus; Cognitive Dysfunction; Oligodendroglia; Humans; Astrocytes; Female
PubMed: 38932491
DOI: 10.1111/cts.13858