The control systems: nervous and endocrine
Nick Draper, Helen Marshall in Exercise Physiology, 2014
Neurons vary greatly in both length and diameter depending on their function within the body. Some nerve cells, such as those responsible for bringing about muscular contraction of the lower leg and feet, are over one metre in length. Like other cells within the body, the cell body (soma or perikaryon) comprises of a cell membrane, a nucleus and cytoplasm. The plasma membrane of the cell body and dendrites is called the neurilemma. However, the cell membrane of the axon is usually referred to as the axolemma because the function of axons necessitates differences in structure when compared with the rest of the cell. In a similar way the cytoplasm of the cell body is known as neuroplasm whereas that in the axon is called axoplasm. The cytoplasm of neurons contains many organelles common to other cells, such as lysosomes, ribosomes, mitochondria and a Golgi apparatus. In addition to generalised organelles, they contain some neuron-specific components, such as neurofibrils, neuron-specific microtubules and Nissl bodies. Neurofibrils are comprised of protein filaments and are designed to maintain the structure of the cell body. The neuron-specific microtubules provide a transport structure through which substances pass between the cell body and the axon. Nissl bodies are small rough endoplasmic reticulum structures that are responsible for synthesising proteins to be used for growth and repair.
Historical concepts of Alzheimer’s disease and dementia
Howard H. Feldman in Atlas of Alzheimer's Disease, 2007
The rapidity of degeneration and relatively young age of the patient made this clinical course unusual, and prompted Dr Alzheimer to investigate the neuropathologic features. One quarter to one third of cerebral cortical neurons had disappeared, and many of the remaining neurons contained thick, coiled tangles of fibrils within their cytoplasm. Using the Bielschowsky silver method, Dr Alzheimer observed intense staining of the neurofibrils and speculated that a chemical change had occurred. Furthermore, Dr Alzheimer suggested that the fibrils led to the eventual death of the cells, leaving the ‘tangle’ as a marker of cell death. In addition to the stained neurofibrillary tangles and accompanying neuronal degeneration, Dr Alzheimer noted the widespread presence of plaque pathology matching the original description of ‘miliary sclerosis’ by Marinescu et al in 1898.2
Internet Pornography: Addiction or Sexual Dysfunction?
Philipa A Brough, Margaret Denman in Introduction to Psychosexual Medicine, 2019
Thus, dopamine can be seen not as the pleasure chemical that dictates ‘liking’ of a substance or behaviour, but the driver, the fuel for craving. The reward, as described, is the prospect of pleasure rather than the pleasure itself (12). Modification of the system occurs through the ‘steady on’ influence of neurotransmitters such as glutamate and GABA. However, these modifying influences can be overwhelmed when there is endless novelty available. Continuous stimulation of the system results in repeated spiking of dopamine levels, which then serves to reinforce the appetite. Just as in drug addiction where the exogenous drugs of abuse compete for certain dopamine (D2) receptor sites, so do endogenous neurotransmitters, produced by the positive emotional effects of ‘natural’ rewards. The pathways would appear to be shared (13). Reduction in the D2 dopamine receptors causes escalation as the subject tries to potentiate and recreate the high (14). Prolonged disruption of the neuronal pathways appears to cause a physical change and reduction of the neurofilament proteins.
Molecular mechanisms governing axonal transport: a C. elegans perspective
Published in Journal of Neurogenetics, 2020
Amruta Vasudevan, Sandhya P. Koushika
In C. elegans, intermediate filaments, such as IFP-1 and IFA-4, have been reported to stabilize microtubules in DD motor neurons, and inhibit synaptic vesicle transport during neuronal remodelling (Kurup, Li, Goncharov, & Jin, 2018). By contrast, another study in C. elegans identified and characterized a novel neurofilament protein, TAG-63, which has been demonstrated to promote the anterograde transport of synaptic cargo (Figure 3(b)) by regulating the run length, velocity and flux of UNC-104/Kinesin-3 and SNB-1-containing synaptic vesicles (Bhan et al., 2019). This study is the first to report a direct role for neurofilament proteins in regulating the motility characteristics of axonal cargo in vivo. The exact nature of this regulation warrants further study, as it is not known whether it occurs via regulation of microtubule stability or direct interactions with the cargo-motor complex.
Polysaccharide of Taxus chinensis var. mairei Cheng et L.K.Fu attenuates neurotoxicity and cognitive dysfunction in mice with Alzheimer’s disease
Published in Pharmaceutical Biology, 2020
Senwei Zhang, Lulu Li, Jinting Hu, Ping Ma, Huimin Zhu
Intertwining of neurofibrils, loss of neurons and senile plaque formation are important pathological features in the brain of AD patients (Chandra 2017). Aβ is considered to be the most important component of senile plaque (Chandra 2017). Excessive Aβ deposits outside the cortex and hippocampal neurons, forming plaque tangles that lead to abnormal synaptic function, loss of nerve cells and inflammation, eventually leading to neurological structural and functional disorders and the formation of dementia (Nasica-Labouze et al. 2015). Besides, abnormal Aβ is able to induce apoptosis and neurotoxicity (Lee et al. 2013; Porcellotti et al. 2015). Interestingly, Aβ may affect cell apoptosis by regulating the activity of caspase-3, which plays an irreplaceable role in the process of apoptosis (Chang et al. 2016). Our results indicated that PTM treatment could reduce Aβ expression and apoptosis-related protein cleaved caspase-3 and Bax/Bcl-2 ratio in AD-like mice.
Accelerating Alzheimer’s disease drug discovery and development: what’s the way forward?
Published in Expert Opinion on Drug Discovery, 2021
Bruno P. Imbimbo, Stefania Ippati, Mark Watling, Claudia Balducci
Most of the drugs that have failed to show cognitive and clinical benefits in large clinical trials have shown significant effects on AD biomarkers (brain Aβ plaques, CSF Aβ, or tau levels) that are relevant to their intended mechanism of action. Typical examples are BACE1 inhibitors that dramatically reduced CSF Aβ levels, even while worsening cognition, behavior and even brain atrophy, rather than improving them [19]. Another example is the previously mentioned human IgG1 monoclonal antibody gantenerumab, which recognizes fibrillary forms of Aβ. In a 4-year study involving 144 pre-symptomatic or mildly symptomatic subjects who carried ADAD genetic mutations (PSEN1, PSEN2, and APP), the drug failed to demonstrate cognitive or clinical benefits despite a reduction of brain Aβ burden and an increase in CSF Aβ42 levels [12]. The treatment induced positive biomarker effects by significantly decreasing CSF levels of total tau, p-tau181, and neurofilament light chain (NfL), but this did not turn into cognitive benefits [12]. These examples of disconnection between positive effects of anti-Aβ drugs on AD biomarker expression and functional outcomes suggest that current AD biomarkers might represent only terminal biological steps of the AD cascade and their modification does not, or is not sufficient to, reflect the course of the pathological process underlying the disease.