scholarly journals Intranasal Glyphosate-Based Herbicide Administration Alters the Redox Balance and the Cholinergic System in the Mouse Brain

2019 ◽  
Author(s):  
Cristina Eugenia Gallegos ◽  
Mariana Bartos ◽  
Fernanda Gumilar ◽  
Rita Raisman-Vozari ◽  
Alejandra Minetti ◽  
...  
Keyword(s):  
Pesticide Exposure ◽  
Cholinergic Neurons ◽  
Redox Balance ◽  
Medial Septum ◽  
Brain Areas ◽  
Anterior Olfactory Nucleus ◽  
Psychomotor Disorders ◽  
Thiol Content ◽  
Glutamatergic Pathways ◽  
The Brain

ABSTRACTPesticide exposure is associated with cognitive and psychomotor disorders. Glyphosate-based herbicides (GlyBH) are among the most used agrochemicals, and inhalation of GlyBH sprays may arise from frequent aerial pulverizations. Previously, we described that intranasal (IN) administration of GlyBH in mice decreases locomotor activity, increases anxiety, and impairs recognition memory. Then, the aim of the present study was to investigate the mechanisms involved in GlyBH neurotoxicity after IN administration. Adult male CF-1 mice were exposed to GlyBH IN administration (equivalent to 50 mg/kg/day of Gly acid, 3 days a week, during 4 weeks). Total thiol content and the activity of the enzymes catalase, acetylcholinesterase and transaminases were evaluated in different brain areas. In addition, markers of the cholinergic and the nigrostriatal pathways, as well as of astrocytes were evaluated by fluorescence microscopy in coronal brain sections. The brain areas chosen for analysis were those seen to be affected in our previous study. GlyBH IN administration impaired the redox balance of the brain and modified the activities of enzymes involved in cholinergic and glutamatergic pathways. Moreover, GlyBH treatment decreased the number of cholinergic neurons in the medial septum as well as the expression of the α7-acetylcholine receptor in the hippocampus. Also, the number of astrocytes increased in the anterior olfactory nucleus of the exposed mice. Taken together, these disturbances may contribute to the neurobehavioural impairments reported previously by us after IN GlyBH administration in mice.

The Cholinergic Multicompartmental Basal Forebrain Microcircuit

2017 ◽  
pp. 163-184
Author(s):  
Laszlo Zaborszky ◽  
Peter Gombkoto
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Medial Septum ◽  
Cortical Activation ◽  
Ach Release ◽  
Diagonal Band ◽  
Substantia Innominata ◽  
Arousal Effect ◽  
Hippocampal Complex ◽  
The Brain

The basal forebrain (BF) is composed of an affiliation of structures, including the medial septum, ventral pallidum (VP), vertical diagonal band (VDB) and horizontal diagonal band (HDB) nuclei, substantia innominata/extended amygdala (SI/EA), and peripallidal regions. Together, they constitute one of the most extensive multicompartmental microcircuits in the brain. A prominent feature of the mammalian BF is the presence of aggregated and nonaggregated, large, cholinergic neurons, which project to the cerebral cortex, the hippocampal complex, and the amygdala. This highly complex system has been implicated in cortical activation, attention, motivation, and memory, as well as neuropsychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, schizophrenia, and drug abuse. Advances in modern tracing, genetic, and refined pharmacological techniques have dramatically increased the understanding of how the BF cholinergic system can support both phasic acetylcholine (ACh) release in attention, memory, and sensory processing and tonic ACh release over broad cortical areas as part of a general arousal effect.

Current Strategies and Novel Drug Approaches for Alzheimer Disease

2020 ◽  
Vol 19 (9) ◽  
pp. 676-690 ◽  
Author(s):  
Roma Ghai ◽  
Kandasamy Nagarajan ◽  
Meenakshi Arora ◽  
Parul Grover ◽  
Nazakat Ali ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinergic Neurons ◽  
Amyloid Plaque ◽  
Neural Pathways ◽  
Current Trends ◽  
Personality Changes ◽  
Traditional Therapies ◽  
Novel Drug ◽  
The Brain

Alzheimer’s Disease (AD) is a chronic, devastating dysfunction of neurons in the brain leading to dementia. It mainly arises due to neuronal injury in the cerebral cortex and hippocampus area of the brain and is clinically manifested as a progressive mental failure, disordered cognitive functions, personality changes, reduced verbal fluency and impairment of speech. The pathology behind AD is the formation of intraneuronal fibrillary tangles, deposition of amyloid plaque and decline in choline acetyltransferase and loss of cholinergic neurons. Tragically, the disease cannot be cured, but its progression can be halted. Various cholinesterase inhibitors available in the market like Tacrine, Donepezil, Galantamine, Rivastigmine, etc. are being used to manage the symptoms of Alzheimer’s disease. The paper’s objective is to throw light not only on the cellular/genetic basis of the disease, but also on the current trends and various strategies of treatment including the use of phytopharmaceuticals and nutraceuticals. Enormous literature survey was conducted and published articles of PubMed, Scifinder, Google Scholar, Clinical Trials.org and Alzheimer Association reports were studied intensively to consolidate the information on the strategies available to combat Alzheimer’s disease. Currently, several strategies are being investigated for the treatment of Alzheimer’s disease. Immunotherapies targeting amyloid-beta plaques, tau protein and neural pathways are undergoing clinical trials. Moreover, antisense oligonucleotide methodologies are being approached as therapies for its management. Phytopharmaceuticals and nutraceuticals are also gaining attention in overcoming the symptoms related to AD. The present review article concludes that novel and traditional therapies simultaneously promise future hope for AD treatment.

Aetiologies and anatomy of confabulation

2017 ◽  
Author(s):  
Armin Schnider
Keyword(s):  
Brain Damage ◽  
Limbic Encephalitis ◽  
Artery Aneurysm ◽  
Anterior Communicating Artery ◽  
Brain Areas ◽  
Anatomical Basis ◽  
Korsakoff Syndrome ◽  
Hypoxic Brain ◽  
Degenerative Dementia ◽  
The Brain

What diseases cause confabulations and which are the brain areas whose damage is responsible? This chapter reviews the causes, both historic and present, of confabulations and deduces the anatomo-clinical relationships for the four forms of confabulation in the following disorders: alcoholic Korsakoff syndrome, traumatic brain injury, rupture of an anterior communicating artery aneurysm, posterior circulation stroke, herpes and limbic encephalitis, hypoxic brain damage, degenerative dementia, tumours, schizophrenia, and syphilis. Overall, clinically relevant confabulation is rare. Some aetiologies have become more important over time, others have virtually disappeared. While confabulations seem to be more frequent after anterior brain damage, only one form has a distinct anatomical basis.

scholarly journals Limbic Expression of mRNA Coding for Chemoreceptors in Human Brain—Lessons from Brain Atlases

2021 ◽  
Vol 22 (13) ◽  
pp. 6858
Author(s):  
Fanny Gaudel ◽  
Gaëlle Guiraudie-Capraz ◽  
François Féron
Keyword(s):  
G Proteins ◽  
The Body ◽  
Trace Amines ◽  
Chemical Senses ◽  
Brain Areas ◽  
Genes Encoding ◽  
The Central Nervous System ◽  
Human Brains ◽  
The Brain ◽  
Brain Atlases

Animals strongly rely on chemical senses to uncover the outside world and adjust their behaviour. Chemical signals are perceived by facial sensitive chemosensors that can be clustered into three families, namely the gustatory (TASR), olfactory (OR, TAAR) and pheromonal (VNR, FPR) receptors. Over recent decades, chemoreceptors were identified in non-facial parts of the body, including the brain. In order to map chemoreceptors within the encephalon, we performed a study based on four brain atlases. The transcript expression of selected members of the three chemoreceptor families and their canonical partners was analysed in major areas of healthy and demented human brains. Genes encoding all studied chemoreceptors are transcribed in the central nervous system, particularly in the limbic system. RNA of their canonical transduction partners (G proteins, ion channels) are also observed in all studied brain areas, reinforcing the suggestion that cerebral chemoreceptors are functional. In addition, we noticed that: (i) bitterness-associated receptors display an enriched expression, (ii) the brain is equipped to sense trace amines and pheromonal cues and (iii) chemoreceptor RNA expression varies with age, but not dementia or brain trauma. Extensive studies are now required to further understand how the brain makes sense of endogenous chemicals.

scholarly journals Crucial Role of FABP3 in αSyn-Induced Reduction of Septal GABAergic Neurons and Cognitive Decline in Mice

2021 ◽  
Vol 22 (1) ◽  
pp. 400
Author(s):  
Kazuya Matsuo ◽  
Yasushi Yabuki ◽  
Ronald Melki ◽  
Luc Bousset ◽  
Yuji Owada ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Processing ◽  
Dopaminergic Neurons ◽  
Dorsal Striatum ◽  
Cholinergic Neurons ◽  
Medial Septum ◽  
Gabaergic Neurons ◽  
Gamma Aminobutyric Acid ◽  
Fatty Acid Binding

In synucleinopathies, while motor symptoms are thought to be attributed to the accumulation of misfolded α-synuclein (αSyn) in nigral dopaminergic neurons, it remains to be elucidated how cognitive decline arises. Here, we investigated the effects of distinct αSyn strains on cognition and the related neuropathology in the medial septum/diagonal band (MS/DB), a key region for cognitive processing. Bilateral injection of αSyn fibrils into the dorsal striatum potently impaired cognition in mice. The cognitive decline was accompanied by accumulation of phosphorylated αSyn at Ser129 and reduction of gamma-aminobutyric acid (GABA)-ergic but not cholinergic neurons in the MS/DB. Since we have demonstrated that fatty acid-binding protein 3 (FABP3) is critical for αSyn neurotoxicity in nigral dopaminergic neurons, we investigated whether FABP3 also participates in αSyn pathology in the MS/DB and cognitive decline. FABP3 was highly expressed in GABAergic but rarely in cholinergic neurons in the MS/DB. Notably, Fabp3 deletion antagonized the accumulation of phosphorylated αSyn, decrease in GABAergic neurons, and cognitive impairment caused by αSyn fibrils. Overall, the present study indicates that FABP3 mediates αSyn neurotoxicity in septal GABAergic neurons and the resultant cognitive impairment, and that FABP3 in this subpopulation could be a therapeutic target for dementia in synucleinopathies.

scholarly journals Initiators of Classical and Lectin Complement Pathways Are Differently Engaged after Traumatic Brain Injury—Time-Dependent Changes in the Cortex, Striatum, Thalamus and Hippocampus in a Mouse Model

2020 ◽  
Vol 22 (1) ◽  
pp. 45
Author(s):  
Agata Ciechanowska ◽  
Katarzyna Ciapała ◽  
Katarzyna Pawlik ◽  
Marco Oggioni ◽  
Domenico Mercurio ◽  
...  
Keyword(s):  
Brain Injury ◽  
Microglial Cell ◽  
Lectin Pathway ◽  
Brain Areas ◽  
Mannose Binding ◽  
Primary Microglial Cell ◽  
Cellular Markers ◽  
The Brain ◽  
Binding Lectin ◽  
Complement Pathways

The complement system is involved in promoting secondary injury after traumatic brain injury (TBI), but the roles of the classical and lectin pathways leading to complement activation need to be clarified. To this end, we aimed to determine the ability of the brain to activate the synthesis of classical and lectin pathway initiators in response to TBI and to examine their expression in primary microglial cell cultures. We have modeled TBI in mice by controlled cortical impact (CCI), a clinically relevant experimental model. Using Real-time quantitative polymerase chain reaction (RT-qPCR) we analyzed the expression of initiators of classical the complement component 1q, 1r and 1s (C1q, C1r, and C1s) and lectin (mannose binding lectin A, mannose binding lectin C, collectin 11, ficolin A, and ficolin B) complement pathways and other cellular markers in four brain areas (cortex, striatum, thalamus and hippocampus) of mice exposed to CCI from 24 h and up to 5 weeks. In all murine ipsilateral brain structures assessed, we detected long-lasting, time- and area-dependent significant increases in the mRNA levels of all classical (C1q, C1s, C1r) and some lectin (collectin 11, ficolin A, ficolin B) initiator molecules after TBI. In parallel, we observed significantly enhanced expression of cellular markers for neutrophils (Cd177), T cells (Cd8), astrocytes (glial fibrillary acidic protein—GFAP), microglia/macrophages (allograft inflammatory factor 1—IBA-1), and microglia (transmembrane protein 119—TMEM119); moreover, we detected astrocytes (GFAP) and microglia/macrophages (IBA-1) protein level strong upregulation in all analyzed brain areas. Further, the results obtained in primary microglial cell cultures suggested that these cells may be largely responsible for the biosynthesis of classical pathway initiators. However, microglia are unlikely to be responsible for the production of the lectin pathway initiators. Immunofluorescence analysis confirmed that at the site of brain injury, the C1q is localized in microglia/macrophages and neurons but not in astroglial cells. In sum, the brain strongly reacts to TBI by activating the local synthesis of classical and lectin complement pathway activators. Thus, the brain responds to TBI with a strong, widespread and persistent upregulation of complement components, the targeting of which may provide protection in TBI.

Comparing the brain areas supporting nondeclarative categorization and recognition memory

2002 ◽  
Vol 14 (2) ◽  
pp. 245-257 ◽  
Author(s):  
Paul J Reber ◽  
Eric C Wong ◽  
Richard B Buxton
Keyword(s):  
Recognition Memory ◽  
Brain Areas ◽  
The Brain

Cannabidiol Has a Unique Effect on Global Brain Activity: A Pharmacological, Functional MRI Study in Awake Mice 

2021 ◽  
Author(s):  
Aymen Sadaka ◽  
Ana Ozuna ◽  
Richard Ortiz ◽  
Praveen Kulkarni ◽  
Clare Johnson ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Brain Activity ◽  
Stress Disorders ◽  
Functional Coupling ◽  
Specific Information ◽  
Imaging Data ◽  
Post Traumatic Stress ◽  
Brain Areas ◽  
Dose Dependent ◽  
The Brain

Abstract Background: The phytocannabinoid cannabidiol (CBD) is a potential treatment for post-traumatic stress disorders. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neural circuitry associated with fear and defense. Methods: During the scanning session awake mice were given vehicle or CBD (3, 10, or 30 mg/kg I.P.) and imaged for 10 min post treatment. Mice were also treated with the 10 mg/kg dose of CBD and imaged one hr later for resting state BOLD functional connectivity (rsFC). Imaging data were registered to a 3D MRI mouse atlas providing site-specific information on 138 different brain areas. Blood samples were collected for CBD measurements.Results: CBD produced a dose-dependent polarization of activation along the rostral-caudal axis of the brain. The olfactory bulb and prefrontal cortex showed an increase in positive BOLD whereas the brainstem and cerebellum showed a decrease in BOLD signal. This negative BOLD affected many areas connected to the ascending reticular activating system (ARAS). The ARAS was decoupled to much of the brain but was hyperconnected to the olfactory system and prefrontal cortex. The pattern of ARAS connectivity closely overlapped with brain areas showing high levels N-acyl-phosphatidylethanolamines-specific phospholipase D (NAPE-PLD) messenger RNA.Conclusion: The CBD-induced decrease in ARAS activity is consistent with an emerging literature suggesting that CBD reduces autonomic arousal under conditions of emotional and physical stress. The putative target and mechanism of action is NAPE-PLD the enzyme responsible for the biosynthesis of lipid signaling molecules like anandamide.

scholarly journals Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas

2017 ◽  
Vol 39 (2) ◽  
pp. 98-105 ◽  
Author(s):  
Paula Madeira Fortes ◽  
Lucas Albrechet-Souza ◽  
Mailton Vasconcelos ◽  
Bruna Maria Ascoli ◽  
Ana Paula Menegolla ◽  
...  
Keyword(s):  
Aggressive Behavior ◽  
Physiological Responses ◽  
Plasma Corticosterone ◽  
Corticotropin Releasing Factor ◽  
Brain Areas ◽  
Social Stressors ◽  
Swiss Mice ◽  
The Brain ◽  
Over Time ◽  
Resident Intruder

Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

scholarly journals Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Alessio Molfino ◽  
Gianfranco Gioia ◽  
Filippo Rossi Fanelli ◽  
Alessandro Laviano
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Proinflammatory Cytokines ◽  
Adaptive Response ◽  
Energy Homeostasis ◽  
Cancer Cachexia ◽  
Behavioral Changes ◽  
Brain Areas ◽  
Functional Changes ◽  
The Brain

Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.

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