MPTP Mouse Model

“There is evidence that PME directly affects the development of the central nervous system (CNS) in both animals and humans” (Day, Goldschmidt & Thomas, 2006).

To setup a repetitive concussive model that replicate the important features of the injury in humans as closely as possible, post-concussion symptoms are expected. Post-concussion symptoms generally include somatic symptoms, sleep disturbance, and emotional and cognitive symptoms. Since somatic symptoms such as headache, nausea, and dizziness may not be ready to be measured in animal models, the changes of motor function, cognitive function, and emotional behavior are used as criteria for rationally evaluating animal models of concussion. In a previous reported study, this rCHI mouse model induces spatial learning and memory impairments as well as anxiety-like behavior, which resemble those observed in human mTBI patients [8]. More importantly,

PD is the second most common neurodegenerative disease featured pathologically by the progressive loss of dopaminergic neurons in the substantia nigra. The typical symptoms of PD include slowness of movements (bradykinesia), muscle stiffness (rigidity), tremor, and balance disturbance. Etiopathologically, PD is considered to be caused by the significant loss of dopaminergic neurons in the substantia nigra pars compacta and the subsequent dopamine depletion at the striatum. To date, there are only symptomatic treatments available for PD, particularly in the early stages of the disease. No therapy has been found that can cure or halt the progression of the disease.

In the essay From Inside the Mouse: Work and Play at Disney World, the writer, Anna

The elevated striatal dopamine levels induced by rasagiline-dependent MAO-B inhibition has been correlated to improvements in PD motor symptoms in both monotherapy and adjunctive therapy studies. The TEMPO (TVP-2012 in Early Monotherapy for Parkinson’s Disease Outpatients) study, a 26-week, randomized, double-blind and placebo-controlled clinical trial observed the efficacy of rasagiline as a monotherapy for 404 early PD patients. Efficacy of rasagiline was quantified using the Unified Parkinson’s Disease Rating Scale (UPDRS), a rating scale used to measure the progression of PD by scoring four primary categories of symptoms: mentation, behavior and mood; activities of daily living; motor examination; and complications of therapy. Higher UPDRS scores correspond to greater severity of disease with the maximum possible score of 199 points representing total disability. The patients in the TEMPO trial had a mean baseline UPDRS score of 25 points and were subsequently divided into three groups: 1 mg rasagiline qd, 2 mg rasagiline qd or placebo. At the end of the trial period, compared with the placebo group, the average change in total UPDRS score was -3.56 for the 2 mg rasagiline group and -4.20 for the 1 mg rasagiline group. Of the four UPDRS categories, the greatest change was observed in the motor examination sub-scale with a mean change of -2.71 for the 1 mg rasagiline group and -1.68 for the 2 mg rasagiline group. This reduction in UPDRS score, especially with regards to

Smallpox is an acute contagious viral disease that has a relatively high fatality rate in immunologically naive populations. It is caused by variola virus, which is a member of a larger pox family of viruses. Smallpox can manifest itself in two clinical forms (variola major and variola minor) and it can be transmitted from person to person. There is no specific treatment for this disease other than the management of symptoms.

It has been well established that α- synuclein plays a role in the pathogenesis of PD (Spillantini MG et al., 1997; Wakabayashi et al 2007; Polymeropoulos MH et al., 1997; Singelton et al., 2003; Maries E et al., 2003). α-synuclein accumulates within the SN neurons, where it is trapped inside granules of pigments during the synthesis of neuromelanin much before there is evidence that neuromelanin is depleted in PD (Fasano M et al, 2003; Ikemura M et al, 2008; Michell AW et al., 2005). In PD, the peripheral nervous system (PNS) is also affected which is demonstrated by the fact that α-synuclein is also found in aggregates throughout the nervous system, including, enteric nervous system, sympathetic ganglia, submandibular gland, cardiac and pelvic plexuses, the skin and adrenal medulla (Shishido et al, 2010; Wakabayashi et al., 2010). It has been shown that α-synuclein immunoreactivity is increased in cutaneous peripheral nerves of PD when compared to those with other neurodegenerative disorders (Paisan Ruiz et al., 2009).

If nothing else, the lesson that can be taken from the connection between Hebb’s postulate in 1949 and the discovery of LPT in 1973 is that the advancements in the neurobiological field of medicine can applied to previous theories and start to offer new ways to alleviate the symptoms that come with diseases such as Huntington’s and Parkinson’s. In a groundbreaking study, the alleviating effects of both THC and CBD were studied on rats who were injected with 6-hydroxydopamine (Lastres-Becker, Molina-Holgado, Ramos, Mechoulam, and Fernandez-Ruiz, 2005). This drug has been found to induce Parkinson’s disease-like conditions. Based on previous studies on the effectiveness of these cannabinoids on protecting neurons from neurotoxicity, the

Our laboratory has developed the mucosal MmuPV1 infection mouse model recently and noninvasive methods to track the infection from oral and anogenital canals longitudinally [14]. Our long term goal is to use this model to explore many unanswered questions regarding viral-host interaction during papillomavirus infection. Innate immunity, a critical part of host defense system, is not only the first line of defense against pathogens, but is also critical for stimulating adaptive immune responses in viral infection [15-22]. Other host defense factors including interferons, Toll-like receptors, cytokines and defensins all play an important role in papillomavirus persistence and progression [23-31]. However, some findings in human studies are inconsistent

Because of the low heritability of PD, more studies focusing on environmental exposures about the PD mechanism (AH-2012). Researchers may focus on both chemical hazards and physical hazards (AH-2012). Exposure to environmental factors or mutations in PD-associated genes of patients may cause mitochondrial dysfunction that ultimately results in PD. All of these share common linkages and influence each other greatly. Limiting the early inflammatory response will reduce further both elevated oxidative stress and microglial activation that are key to slowing the death of the neurons in the SNpc.

The neurodegenerative disease is the disease in which the neurons become degenerate and causing death of neurons. The Alzheimer’s disease is the first most common neurodegenerative disease. The Alzheimer’s disease is firstly described by Alois Alzheimer in (1907) because of this it named Alzheimer’s. The Parkinson’s disease is the second most common neurodegenerative disease National Institute of Environmental Health Sciences (NIEHS). Alzheimer’s disease is the first most common neurodegenerative disease and the (Yanker, 1996) studied the Alzheimer’s disease neuronal degeneration and the mechanism of this disease. The dopamine neurons degenerate when the neurotoxin induced in the Caenorhabditis elegans (Francis et al., 1999). The 95% Parkinson’

This was achieved upon administering the neurotoxin through a systemic injection but direct intracerebral injection produces neuronal lesions as the neurotoxin is unable to cross the blood brain barrier so administration for models is a vital step in order to produce Parkinsons symptoms. The preferred locations in the brain for injection are the substania nigra, striatum or the medial forebrain which is a common root for rat models, these locations reflect the motor defifcts associated with parkjinsons by dopamine depletion in the striatum and destruction of the dopaminergic neurons (Blum et al., 2001). What makes this neurotoxin more benifical is that it has been found to be a endogenous neurotoxin in both rat and human brains reflecting similarities which aid in rat models being a nobel model (Senoh et al.,

Strangely they has been a case where patients suffered from PMD phenotype of adult onset. The case involved two brothers who had a late onset of the disease at the ages of 29 and 42 years. They suffered the same chronic neurological symptoms including ataxia, dementia and tremor. The two brothers lived up to the ages of 45 and 61, and their post-mortem examinations showed very similar results to those expected from a person who suffered from PMD. The results showed hypomyelination in large parts of white matter, oligodendrites were numerically reduced, and immunhistochemistry showed that PLP reductions in affected white matter. Genetic study did not show any mutations or duplications of the PLP1 gene. It was concluded that "the

As previously discussed, the basal ganglia circuit is an important aspect of the pathophysiology of PD. There are five dopamine receptors that are found in the basal ganglia. They are categorized from D1 to D5. D1 and D2 are most significant with relation to the pathophysiology of PD. They are found primarily within motor stratum. These receptors have denervation hypersensitivity due to dopaminergic neuron deficiency. The dopamine producing neurons decrease significantly as the disease process advances, resulting in the depletion of dopamine in the nigrostriatal pathway and the substantia nigra. The subthalamic nucleus is not inhibited due to this hypersensitivity. his can lead to heightened inhibition in the thalamus, causing instability of

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized mainly by physical and psychological disabilities. This disorder was named after James Parkinson, an English physician who first described it as shaking palsy in 1817 (Goetz, Factr, and Weiner, 2002). Jean- Martin Charcot, who was a French neurologist, then progressed and further refined the description of the disease and identified other clinical features of PD (Goetz, Factr, and Weiner, 2002). PD involves the loss of cells that produce the neurotransmitter dopamine in a part of the brain stem called the substansia nigra, which results in several signs and symptoms (Byrd, Marks, and Starr, 2000). It is manifested clinically by tremor,