实验仪器使用技术

Specific cellular and temporal regulation of gene expression is a goal of many molecular studies. The study of programmed cell death requires cellular specificity, temporal regulation, as well as the interaction of a myriad of gene products. One way to regulate these interactions in an apopt ...

Apoptosis is a physiological process that contributes to the establishment and homeostasis of the nervous system. For example, neurons that fail to make the proper connections with their postsynaptic targets die naturally during development due to the lack of sufficient trophic supp ...

In recent years substantial evidence has accumulated demonstrating a central regulatory role for mitochondria in cell death (1). More recently, mechanisms of cell death, through apoptosis, have been elucidated and increasingly point toward mitochondria as the gatekeepers of apo ...

Bax is a proapoptotic member of the Bcl-2 family. Members of this family can promote either cell survival, as in the case of Bcl-2 and Bcl-XL, or cell death, as in the case of Bax and Bak. Bax was first identified as a Bcl-2 binding partner by immunoprecipitation (1). Subsequently it was shown that overexpression ...

Dogma suggests that cell death mechanisms can present with either a necrotic or an apoptotic phenotype. Recent evidence, however, seems to point to a far more complex picture, in which apoptotic and necrotic phenotypes might present simultaneously (1). For example, TUNEL positivity in car ...

Neuronal apoptosis plays a significant role in nervous system development and in neuropathological conditions (1). Although apoptosis is not the only type of non-necrotic, regulated cell death observed in the nervous system, it is by far the most extensively investigated (2,3). Studies in a ...

Essentially three modes of synaptic elimination have been described (1): (1) loss of synapses in synaptically connected neurons following physiological neuron death during development or hormonally driven reorganization; (2) process (generally axonal) retraction and prot ...

Alzheimer’s disease (AD) is nowadays the most widespread form of senile dementia in Western countries. AD is considered a multifactorial disease: in fact, it is probable that many concomitant factors (genetic and environmental) are relevant in the pathogenesis of this disease. In partic ...

Alcoholic dementia is a disorder characterized by multiple cognitive deficits that include memory impairment associated with one or more cognitive disturbances listed in the present text. First, we characterize the disorder and describe aspects of using nonhuman models for study ...

Dementia in humans following traumatic brain injury (TBI) has been well documented in clinical populations, either after a single TBI or repeated mild TBI (rMTBI). In most cases, trauma-induced dementia follows a slow, chronic time-course, and in many cases mild injuries accumulate over ti ...

Normal Pressure Hydrocephalus (NPH) is a syndrome of dementia, gait disturbances, and urinary incontinence affecting the elderly population. Neuroimaging shows ventriculomegaly, and from the 70s to the early 90s invasive testing of intracranial pressure (ICP) and cerebrospin ...

Arterial hypertension is a well-known risk factor for stroke and cognitive deterioration of vascular origin, including vascular cognitive impairment (VCI) and vascular dementia (VaD). Patients with ischemic VaD have a significantly greater incidence of hypertension than pat ...

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a human genetic syndrome that causes multiple small strokes, due to a single-gene, autosomal dominant mutation with 100% penetrance. CADASIL mutations encode amino acid ...

Frontotemporal dementia (FTD) is a multifaceted syndrome with a high degree of clinical and �neuropathological variability, an extensive genetic contribution, and involvement of multiple proteins. FTD accounts for up to 50% of dementias with the onset prior to age 60. The heterogeneous ...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective death of motor neurons. Although ALS is predominantly a disease of motor system degeneration, cognitive impairments have also been reported. In order to determine the pathogenic m ...

Metachromatic leukodystrophy (MLD) and adrenoleukodystrophy (ALD) are two inherited �leukodystrophies that result in most cases in rapid destruction of the myelin within the central nervous system. There are no spontaneous animal models of these two leukodystrophies and knoc ...

Parkinson’s disease (PD) is primarily recognized as a motor disorder; however, patients also present with a wide range of nonmotor manifestations. Cognitive dysfunctions in nondemented PD patients can occur early in the disease and primarily consist of deficits in executive function. ...

Alzheimer’s disease (AD) is a devastating disease, and the most common form of dementia to afflict the elderly population. The disease causes a slow but progressive neurodegeneration, leading to memory impairments and dysfunction in other cognitive domains. The molecular mechanism of ...

Tau pathology refers to molecular mechanisms leading to the intracellular aggregation of abnormally modified Tau protein isoforms and to the propagation of this degenerating process along neuronal �circuitry. Tau proteins belong to the family of microtubule-associated prot ...

Producing a valid animal model of apolipoprotein E (APOE )-based dementia is critical to understanding the etiology and progression of late-onset Alzheimer’s disease (AD). Unfortunately, no such model exists. Herein, I review all past and present attempts to create an APOE-based model wi ...