scholarly journals Norepinephrine May Oppose Other Neuromodulators to Impact Alzheimer’s Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7364
Author(s):  
Paul J. Fitzgerald
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biomedical Research ◽  
Response Curve ◽  
The Other ◽  
Molecular Pathways ◽  
Pharmacological Agents ◽  
Extracellular Signaling ◽  
Health And Disease ◽  
The Brain

While much of biomedical research since the middle of the twentieth century has focused on molecular pathways inside the cell, there is increasing evidence that extracellular signaling pathways are also critically important in health and disease. The neuromodulators norepinephrine (NE), serotonin (5-hydroxytryptamine, 5HT), dopamine (DA), acetylcholine (ACH), and melatonin (MT) are extracellular signaling molecules that are distributed throughout the brain and modulate many disease processes. The effects of these five neuromodulators on Alzheimer’s disease (AD) are briefly examined in this paper, and it is hypothesized that each of the five molecules has a u-shaped (or Janus-faced) dose-response curve, wherein too little or too much signaling is pathological in AD and possibly other diseases. In particular it is suggested that NE is largely functionally opposed to 5HT, ACH, MT, and possibly DA in AD. In this scenario, physiological “balance” between the noradrenergic tone and that of the other three or four modulators is most healthy. If NE is largely functionally opposed to other prominent neuromodulators in AD, this may suggest novel combinations of pharmacological agents to counteract this disease. It is also suggested that the majority of cases of AD and possibly other diseases involve an excess of noradrenergic tone and a collective deficit of the other four modulators.

scholarly journals Sex Differences and the Influence of Sex Hormones on Cognition through Adulthood and the Aging Process

2018 ◽  
Vol 8 (9) ◽  
pp. 163 ◽  
Author(s):  
Caroline Gurvich ◽  
Kate Hoy ◽  
Natalie Thomas ◽  
Jayashri Kulkarni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Functioning ◽  
Sex Hormones ◽  
Reproductive Function ◽  
Health And Disease ◽  
And Function ◽  
The Brain

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided.

scholarly journals Alzheimer's Disease: A Survey

2021 ◽  
Vol 8 (1) ◽  
pp. 33-39
Author(s):  
Harshitha ◽  
Gowthami Chamarajan ◽  
Charishma Y
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Deep Neural Networks ◽  
Brain Area ◽  
Brain Mri ◽  
Three Dimensional ◽  
The Other ◽  
Machine Learning Techniques ◽  
Learning Techniques ◽  
The Brain

Alzheimer's Diseases (AD) is one of the type of dementia. This is one of the harmful disease which can lead to death and yet there is no treatment. There is no current technique which is 100% accurate for the treatment of this disease. In recent years, Neuroimaging combined with machine learning techniques have been used for detection of Alzheimer's disease. Based on our survey we came across many methods like Convolution Neural Network (CNN) where in each brain area is been split into small three dimensional patches which acts as input samples for CNN. The other method used was Deep Neural Networks (DNN) where the brain MRI images are segmented to extract the brain chambers and then features are extracted from the segmented area. There are many such methods which can be used for detection of Alzheimer’s Disease.

Mitochondria in Neuroplasticity, Neurologic Disease and Aging.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-2-SCI-2 ◽  
Author(s):  
Mark P. Mattson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bone Marrow ◽  
Learning And Memory ◽  
Neuronal Excitability ◽  
Epileptic Seizures ◽  
Receptor Expression ◽  
Health And Disease ◽  
Energy Deprivation ◽  
The Brain

Abstract Abstract SCI-2 Brain cells are influenced in health and disease by several types of bone marrow-derived cells (BMDC) that either reside in, or are recruited to, the brain. Microglia are macrophage-like cells that continuously surveil the brain, and respond to injury, infection or disease by endocytosing damaged/dead cells and microorganisms, and by producing pro-inflammatory cytokines. Lymphocytes of various phenotypes enter the brain in large numbers in response to acute injury (stroke, severe epileptic seizures, trauma) or chronic disease (multiple sclerosis, Alzheimer's disease). While microglia and lymphocytes are best known for their adverse effects on neuronal function and survival in injury or disease (Arumugam et al., Nat Med. 2006; 12:621-3), recent findings suggest that these cells may also serve important beneficial roles in processes such as learning and memory (Ziv et al. Nat Neurosci. 2006; 9:268-75). Here I describe how BMDC can affect neuronal excitability and mitochondrial function in normal physiological settings and in disease states. We have found that low concentrations of tumor necrosis factor (TNF), which is produced by microglia/macrophages and lymphocytes, can promote neuronal survival and synaptic plasticity by activating the transcription factor NF-kB to induce the expression of glutamate receptor subunits, mitochondrial SOD2 and Bcl2 (Mattson and Meffert, Cell Death Differ. 2006; 13:852-60). When bone marrow from TNF receptor-deficient mice was transplanted into irradiated wild type mice, neurons in the brain were more vulnerable to epileptic seizures, suggesting that TNF suppresses neuronal excitability (Guo et al., Neuromolecular Med. 2004; 5:219-34). In other studies we found that a mutation in presenilin-1 (PS1) that causes early-onset inherited Alzheimer's disease (AD) perturbs lymphocyte signaling (Morgan et al., Neuromolecular Med. 2007; 9:35-45). Splenic T cells isolated from PS1 mutant knockin mice respond poorly to proliferative signals and have downregulated cluster designation 3 and interleukin (IL)- 2-receptor expression necessary for a normal T-cell immune response. The adverse effect of mutant PS1 involves perturbed calcium regulation and cytokine signaling in lymphocytes, and associated sensitivity of lymphocytes to mitochondria-mediated apoptosis. These findings suggest that abnormalities in immune function might play roles in the pathogenesis of AD. Finally, I describe very recent findings that suggest roles for toll-like receptor signaling in learning and memory processes, and in neuronal responses to energy deprivation (Tang et al., Proc Natl Acad Sci U S A. 2007; 104:13798-803). Emerging findings therefore suggest that both innate and humoral signaling from BMDC to neurons play interesting roles in regulating neuronal plasticity and energy metabolism in health and disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Time to test antibacterial therapy in Alzheimer’s disease

Brain ◽  
2019 ◽  
Author(s):  
Francesco Panza ◽  
Madia Lozupone ◽  
Vincenzo Solfrizzi ◽  
Mark Watling ◽  
Bruno P Imbimbo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
The Other ◽  
Brain Barrier ◽  
The Past ◽  
Blood Brain ◽  
The Brain

Abstract Alzheimer’s disease is associated with cerebral accumulation of amyloid-β peptide and hyperphosphorylated tau. In the past 28 years, huge efforts have been made in attempting to treat the disease by reducing brain accumulation of amyloid-β in patients with Alzheimer’s disease, with no success. While anti-amyloid-β therapies continue to be tested in prodromal patients with Alzheimer’s disease and in subjects at risk of developing Alzheimer’s disease, there is an urgent need to provide therapeutic support to patients with established Alzheimer’s disease for whom current symptomatic treatment (acetylcholinesterase inhibitors and N-methyl d-aspartate antagonist) provide limited help. The possibility of an infectious aetiology for Alzheimer’s disease has been repeatedly postulated over the past three decades. Infiltration of the brain by pathogens may act as a trigger or co-factor for Alzheimer’s disease, with Herpes simplex virus type 1, Chlamydia pneumoniae, and Porphyromonas gingivalis being most frequently implicated. These pathogens may directly cross a weakened blood–brain barrier, reach the CNS and cause neurological damage by eliciting neuroinflammation. Alternatively, pathogens may cross a weakened intestinal barrier, reach vascular circulation and then cross blood–brain barrier or cause low grade chronic inflammation and subsequent neuroinflammation from the periphery. The gut microbiota comprises a complex community of microorganisms. Increased permeability of the gut and blood–brain barrier induced by microbiota dysbiosis may impact Alzheimer’s disease pathogenesis. Inflammatory microorganisms in gut microbiota are associated with peripheral inflammation and brain amyloid-β deposition in subjects with cognitive impairment. Oral microbiota may also influence Alzheimer’s disease risk through circulatory or neural access to the brain. At least two possibilities can be envisaged to explain the association of suspected pathogens and Alzheimer’s disease. One is that patients with Alzheimer’s disease are particularly prone to microbial infections. The other is that microbial infection is a contributing cause of Alzheimer’s disease. Therapeutic trials with antivirals and/or antibacterials could resolve this dilemma. Indeed, antiviral agents are being tested in patients with Alzheimer’s disease in double-blind placebo-controlled studies. Although combined antibiotic therapy was found to be effective in animal models of Alzheimer’s disease, antibacterial drugs are not being widely investigated in patients with Alzheimer’s disease. This is because it is not clear which bacterial populations in the gut of patients with Alzheimer’s disease are overexpressed and if safe, selective antibacterials are available for them. On the other hand, a bacterial protease inhibitor targeting P. gingivalis toxins is now being tested in patients with Alzheimer’s disease. Clinical studies are needed to test if countering bacterial infection may be beneficial in patients with established Alzheimer’s disease.

scholarly journals Targeting Microglia-Synapse Interactions in Alzheimer’s Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2342
Author(s):  
Gaia Piccioni ◽  
Dalila Mango ◽  
Amira Saidi ◽  
Massimo Corbo ◽  
Robert Nisticò
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Intimate Relationship ◽  
Synapse Loss ◽  
Disease Modifying Therapy ◽  
Inflammatory Signals ◽  
Health And Disease ◽  
Activity Dependent ◽  
The Brain

In this review, we focus on the emerging roles of microglia in the brain, with particular attention to synaptic plasticity in health and disease. We present evidence that ramified microglia, classically believed to be “resting” (i.e., inactive), are instead strongly implicated in dynamic and plastic processes. Indeed, there is an intimate relationship between microglia and neurons at synapses which modulates activity-dependent functional and structural plasticity through the release of cytokines and growth factors. These roles are indispensable to brain development and cognitive function. Therefore, approaches aimed at maintaining the ramified state of microglia might be critical to ensure normal synaptic plasticity and cognition. On the other hand, inflammatory signals associated with Alzheimer’s disease are able to modify the ramified morphology of microglia, thus leading to synapse loss and dysfunction, as well as cognitive impairment. In this context, we highlight microglial TREM2 and CSF1R as emerging targets for disease-modifying therapy in Alzheimer’s disease (AD) and other neurodegenerative disorders.

scholarly journals The Roles of the Microbiome in Alzheimer’s Disease

2021 ◽  
Vol 2 (1) ◽  
pp. 159-167
Author(s):  
Zahin Hafiz ◽  
Moina Malek ◽  
William Ju
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Metabolic Diseases ◽  
The Other ◽  
Therapeutic Interventions ◽  
Brain Barrier ◽  
Therapeutic Implications ◽  
Blood Brain ◽  
The Brain

The gut and the brain are in constant communication in a complex network known as the brain-gut axis. A growing body of research has found links between the brain-gut axis and Alzheimer’s Disease (AD). In this review, we will explore how the mammalian microbiome affects neuroinflammation and increases the permeability of the blood brain barrier in the context of AD. Research shows that the microbiome is associated with neuroinflammation in AD, which is presumably caused by the secretion of cytokines from specialized cells of the brain - microglia and astrocytes. On the other hand, metabolic diseases, caused by microbiota dysbiosis, can increase the permeability of the blood brain barrier. In addition, its higher permeability can allow blood plasma components to enter brain tissue and further develop AD pathology. Findings of the current research have tremendous therapeutic implications. Researchers have speculated whether the therapeutic modification of gut microbiota, through the use of antibiotics and probiotics, may show improvement in AD patients. Our understanding of the pathways and mechanisms involved in the brain-gut axis and AD is still very limited and requires further research before clinical and therapeutic interventions can occur.

scholarly journals Deleterious Alteration of Glia in the Brain of Alzheimer’s Disease

2020 ◽  
Vol 21 (18) ◽  
pp. 6676
Author(s):  
Eunyoung Kim ◽  
Undarmaa Otgontenger ◽  
Ariunzaya Jamsranjav ◽  
Sang Seong Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Genetic Information ◽  
Cellular Communication ◽  
The Other ◽  
Beneficial Effects ◽  
New Findings ◽  
Cellular Factors ◽  
The Brain

The deterioration of neurons in Alzheimer’s disease (AD) arises from genetic, immunologic, and cellular factors inside the cortex. The traditional consensus of the amyloid-beta (Aβ) paradigm as a singular cause of AD has been under revision, with the accumulation of exploding neurobiological evidence. Among the multifaceted casualties of AD, the involvement of glia gains significance for its dynamic contribution to neurons, either in a neuroprotective or neurotoxic fashion. Basically, microglia and astrocytes contribute to neuronal sustainability by releasing neuroprotective cytokines, maintaining an adequate amount of glutamate in the synapse, and pruning excessive synaptic terminals. Such beneficial effects divert to the other detrimental cascade in chronic neuroinflammatory conditions. In this change, there are new discoveries of specific cytokines, microRNAs, and complementary factors. Previously unknown mechanisms of ion channels such as Kv1.3, Kir2.1, and HCN are also elucidated in the activation of microglia. The activation of glia is responsible for the excitotoxicity through the overflow of glutamate transmitter via mGluRs expressed on the membrane, which can lead to synaptic malfunction and engulfment. The communication between microglia and astrocytes is mediated through exosomes as well as cytokines, where numerous pieces of genetic information are transferred in the form of microRNAs. The new findings tell us that the neuronal environment in the AD condition is a far more complicated and dynamically interacting space. The identification of each molecule in the milieu and cellular communication would contribute to a better understanding of AD in the neurobiological perspective, consequently suggesting a possible therapeutic clue.

scholarly journals Physiopathology of Dementia in Iranian Traditional Medicine

2016 ◽  
Vol 21 (4) ◽  
pp. 253-254 ◽  
Author(s):  
Mohammad Mahdi Ahmadian-Attari ◽  
Meysam Shirzad
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Decision Making ◽  
Traditional Medicine ◽  
Animal Studies ◽  
Medical Condition ◽  
The Other ◽  
Iranian Traditional Medicine ◽  
Thinking Ability ◽  
The Brain

Recently, an article published in this journal by Dr Seifaddini and colleagues. In that article, the authors tried to connect dementia, including Alzheimer’s disease, with a condition mentioned in Iranian traditional medical condition, Raoonat and Homgh. In this condition, intellectual functions of the brain are disturbed and therefore, learning and decision-making abilities are damaged. This condition is not age limited and affects thinking ability but not memory. On the other hand, there is a condition described in Iranian traditional medicine, which completely matches with Alzheimer’s disease. This condition is explained under the title of Nesyan (forgetfulness). Nesyan has 5 subdivisions, one of which is caused by the inclination of the brain normal temperament to more coldness and dryness. By performing animal studies, we have recently shown that this kind of Nesyan is related with Alzheimer’s disease. Studies on the traditional recommendations on treatment of this kind of Nesyan can be useful in treatment of Alzheimer’s disease.

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