Abstract：
BACKGROUND:There is widespread loss of acetylcholine and other neurotransmitters in Alzheimer's disease and vascular dementia. It has generally been assumed that death of neurons causes neurotransmitter loss, but alternatively neurotransmitter depletion itself may at least contribute to neurodegeneration. PRESENTATION OF THE HYPOTHESIS:Transgenic mice and pigs with inducible 50% depletion of acetylcholine, dopamine, norepinephrine, serotonin, gamma-aminobutyric acid (GABA) and corticotrophin releasing factor will reproduce Alzheimer's disease or vascular dementia neuropathology, and pharmacologically restoring neurotransmitters will attenuate neuronal injury. TESTING THE HYPOTHESIS:Through nuclear transfer cloning, transgenic mice and pigs would be created with transgenes on one X chromosome, so that transgenes would only be expressed in half of all cells in female animals. Transgenes would encode tetracycline-inducible short hairpin RNA (shRNA) designed to form small interfering RNA (siRNA) to knock down neurotransmitter biosynthesis in late adulthood. Transgene expressing neurons could be readily identified in tissue sections with fluorescent reporter genes. Cholinesterase inhibitors, antidepressants, benzodiazepines and CRF would then be administered in an attempt to rescue degenerating neurons. IMPLICATIONS OF THE HYPOTHESIS:The mice and pigs could serve as an important new model for the pathogenesis of dementia, especially if pharmacologically restoring neurotransmitters rescues degenerating neurons. The animals may also be useful for as models for other disorders such as multi-system atrophy, Parkinson's disease, and depression.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Alisky JMdoi
10.1016/j.mehy.2006.02.043subject
Has Abstractpub_date
2006-01-01 00:00:00pages
556-60issue
3eissn
0306-9877issn
1532-2777pii
S0306-9877(06)00181-2journal_volume
67pub_type
杂志文章abstract：:COVID-19 (coronavirus disease 2019) pandemic due to infection with SARS-CoV-2 has led to the death of thousands of adults worldwide. It is now clear that the hyper-inflammatory response triggered by SARS-CoV-2 plays a major role in disease severity and lethality of the infection. Macrophages are innate immune cells th...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.110073
更新日期：2020-10-01 00:00:00
abstract：:Genetic and environmental influences are both known to be causal factors in the development and maintenance of obesity. Stress related chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and resulting increased glucocorticoid exposure are known to be important pathophysiological mechanisms in the deve...
journal_title：Medical hypotheses
pub_type： 杂志文章,评审
doi：10.1016/j.mehy.2010.10.049
更新日期：2011-03-01 00:00:00
abstract：:Natural objects, live and inanimate, actively maintain their entities by using their capacities (i.e., properties, internal resources, mechanisms, and experience) adequately to their needs. It is suggested that the principle of adequate function is a law of nature. ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(86)90078-2
更新日期：1986-03-01 00:00:00
abstract：:It is proposed here that the initial events in gastric carcinogenesis occur at the junction of the oxyntic and antral mucosae. Intestinal metaplasia represents an adaptive counter-response to early neoplastic change at this site. Chronic gastric ulceration may arise due to the elimination of overtly dedifferentiated c...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(91)90229-r
更新日期：1991-07-01 00:00:00
abstract：:Homocysteinemia, first identified as a genetic disease in children in the 1960s, is associated with severe widespread atherosclerosis which causes death (in untreated cases) before the age of 10 years. Elevated blood homocysteine is now recognized as a risk factor for heart disease in the general population. The mecha...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.2000.1209
更新日期：2001-02-01 00:00:00
abstract：INTRODUCTION:Cardiac resynchronization therapy (CRT) or biventricular pacing (BIVP) has become a common procedure for the treatment of ventricular dyssynchrony in patients with heart failure, particularly in those with bundle branch block patterns (QRS durations >150ms) on the electrocardiogram (ECG). However, a large ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2017.09.026
更新日期：2017-11-01 00:00:00
abstract：:Patients with chronic kidney disease (CKD) experience co-morbid illnesses, including cardiovascular disease and retinopathy. Sevelamer hydrochloride (Renagel®); a non-calcium phosphate binder reduces coronary artery and aortic calcification as compared to calcium containing phosphate binders and additionally effects i...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.12.035
更新日期：2013-04-01 00:00:00
abstract：:Recent articles about the roles and relationships of tissue inhibitor of metalloproteinase-1 and transforming growth factor-beta 1 in various types of normal tissues and malignancies give rise to the question: 'Is there a relationship between them with regard to malignant melanoma progression?' In the light of many re...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.2001.1270
更新日期：2001-08-01 00:00:00
abstract：:Trypanosomiasis (whether African sleeping sickness, or American Chaga's disease) is caused by an infection with a protozoan parasite, i.e. the trypanosome. This carries fatal sequences in the untreated host. Currently available chemotherapeutic drugs (some of which cure by involving reactive oxygen species (ROS] are n...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(91)90142-l
更新日期：1991-11-01 00:00:00
abstract：:Our hypothesis was that testosterone therapy (TT) interacts with previously undiagnosed thrombophilia-hypofibrinolysis, leading to hospitalization for deep venous thrombosis (DVT)-pulmonary emboli (PE). We determined the prevalence of DVT-PE associated with TT 147 men hospitalized in the last 12 months for DVT-PE. Of ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2015.01.020
更新日期：2015-04-01 00:00:00
abstract：:Doppler sonography is used as a routine test for detection of renal artery stenosis (RAS). Although increased peak systolic velocity at the site of the narrowing is a widely accepted method for assessing main renal artery stenosis, tardus parvus phenomenon detected on the downstream blood flow has been used as an alte...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2019.01.016
更新日期：2019-03-01 00:00:00
abstract：:A high incidence of sudden unexplained nocturnal deaths has been reported among young Asian males. These deaths are known as Pokkuri in Japan, Bangungut in the Philippines and Sudden Unexplained Nocturnal Death in the United States. Post mortem analysis has demonstrated cardiac conduction defects in many of the victim...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(88)90071-0
更新日期：1988-06-01 00:00:00
abstract：:Mandibular asymmetry (MA) is one of the most common craniofacial malformations. However, there is no optimal technique for this malformation nowadays. A novel technique for both children and adults with less disadvantages is a must. Parathyroid hormone (PTH) is a straight-chain polypeptide secreted by the parathyroid ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.10.047
更新日期：2010-04-01 00:00:00
abstract：:Structures which morphologically resemble treponemes have been found in material from patients suffering from latent or late latent syphilis, many of whom have received treatment in the past. These structures were also found in the blood or spinal fluid (SF) of asymptomatic patients with both positive and negative ser...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(92)90137-2
更新日期：1992-09-01 00:00:00
abstract：:Seroepidemiological, clinical and molecular findings suggest that the acquired immune deficiency syndrome virus human immunodeficiency virus-1 was introduced into the human species at the time (late 1950s) and in the geographic area (Zaire) in which millions of Africans were vaccinated with attenuated poliomyelitis vi...
journal_title：Medical hypotheses
pub_type： 历史文章,杂志文章
doi：10.1016/s0306-9877(97)90030-x
更新日期：1997-05-01 00:00:00
abstract：BACKGROUND:Huachansu, a Chinese medicine that comes from dried toad venom from the skin glands of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, has been used in treatment of cancers. We conducted a meta-analysis to evaluate the efficacy and safety of Huachansu combined with chemotherapy for advanced gas...
journal_title：Medical hypotheses
pub_type： 杂志文章,meta分析
doi：10.1016/j.mehy.2013.04.038
更新日期：2013-08-01 00:00:00
abstract：:Many clinical trials have clearly demonstrated the benefit of statins in the prevention of coronary heart disease. Although other effects have subsequently been described, the so-called pleiotropic effects of statins, there is a tendency to relate all those effects, more or less directly, to inhibition of 3-hydroxy-3-...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2006.02.046
更新日期：2006-01-01 00:00:00
abstract：:Individuals with Down syndrome (DS) not only have increased risk of hypothyroidism, they also tend to develop a relatively novel mild form of neonatal hypothyroidism. One problem that may predispose those with trisomy 21 to hypothyroidism is the overexpression of the gene DYRK1A, which may have an affect on the thyroi...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2007.01.068
更新日期：2007-01-01 00:00:00
abstract：:Twenty years ago, circumstantial evidence was compiled to link the 1918 pandemic influenza virus to a CNS disorder called epidemic encephalitis or encephalitis lethargica. A challenge was issued to naysayers. During the past two decades, the knowledge about the influenza virus and the 1918 pandemic virus in particular...
journal_title：Medical hypotheses
pub_type： 历史文章,杂志文章
doi：10.1016/j.mehy.2009.12.012
更新日期：2010-05-01 00:00:00
abstract：:Late luteal phase dysphoric disorder is described as a classic biopsychosocial disorder resulting from complex interactions of biological, psychological, socioeconomic and cultural forces on women. To understand women suffering from the disorder, one must understand how the genetically designed female brain and body i...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(93)90236-j
更新日期：1993-09-01 00:00:00
abstract：:The clinical syndrome of hypoxic ischemic encephalopathy (HIE) which occurs in association with birth asphyxia, is thought to represent a reperfusion injury consequent upon the generation of cytotoxic oxygen derived free radicals. It has recently been suggested that resuscitation of asphyxiated infants with unrestrict...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(93)90080-a
更新日期：1993-10-01 00:00:00
abstract：:A role for lipopolysaccharides (endotoxins, LPS) in 7 the pathogenesis of Reye's syndrome (RS) has previously been suggested. Impairment of hepatic LPS clearance can lead to systemic endotoxemia as previous studies by this and other laboratories have suggested for several hepatic disorders including RS. Systemic LPS m...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(92)90115-s
更新日期：1992-11-01 00:00:00
abstract：:An increase in pro-inflammatory cytokines, decrease in endothelial nitric oxide (eNO) and adiponectin levels and an alteration in hypothalamic peptides and gastrointestinal hormones such as incretins and cholecystokinin that regulate satiety, hunger, and food intake occur in metabolic syndrome. Thus, metabolic syndrom...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2010.11.013
更新日期：2011-03-01 00:00:00
abstract：:Hypoxic-ischemic brain injury is an important cause of neonatal mortality and subsequent serious neurological sequel. In neonatal brain the severity of hypoxic injury varies most probably due to the effects of multiple protective or deleterious factors. But the mechanisms under this difference are still not full under...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2008.10.032
更新日期：2009-06-01 00:00:00
abstract：:The amino acid threonine contains two chiral carbons and thus can exist in four possible conformations. However, only a single conformation (2S, 3R) of threonine is incorporated in proteins by the cellular translation material. The conformation at the alpha carbon (carbon 2) is the same as that of the other amino acid...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.2000.1231
更新日期：2001-04-01 00:00:00
abstract：:Diabetic individuals frequently suffer from skin pathologies, especially in their feet. Co-existing peripheral vascular disease and neuropathy exacerbate the capacity of these individuals to cope with infections, minor cuts and wounds, often leading to hard to treat and chronic ulcers. Copper has potent anti-fungal an...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.02.050
更新日期：2009-12-01 00:00:00
abstract：:Music is ubiquitous. Yet, its biological relevance is still an ongoing debate. Supporting the view that music had an ancestral role in courtship displays, a pilot study presented here provides preliminary evidence on the link between music and sexual selection. The underlying hypothesis is based on the fact that the s...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2016.05.030
更新日期：2016-08-01 00:00:00
abstract：:NETosis, being an alternative form of cell death is the creation of web-like chromatin decondensates by suitably primed neutrophils as a response to stimulus aimed at containing and eliminating the same. In certain situations, it causes more harm than benefit in the form of bystander damage directly or via activation ...
journal_title：Medical hypotheses
pub_type： 信件
doi：10.1016/j.mehy.2020.109968
更新日期：2020-11-01 00:00:00
abstract：:The water proton spin lattice relaxation time of normal and tumorous tissues of human and radiosensitivity yield a linear relationship. ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(95)90507-3
更新日期：1995-06-01 00:00:00
abstract：:Schizophrenia, if not the most difficult, is one of the most difficult mysterious puzzles for psychiatrists, psychologists, and neuroscientists to solve. In this paper, based on the previously known pathologies of schizophrenia, a new model is proposed for explanation of the formation of positive psychotic symptoms of...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2006.03.054
更新日期：2006-01-01 00:00:00
