Mptp Animal Model

Parkinson disease (PD), also referred to as Parkinson’s disease and paralysis agitans, is a progressive neurodegenerative disease that is the third most common neurologic disorder of older adults. It is a debilitating disease affecting motor ability and is characterized by four cardinal symptoms: tremor rigidity, bradykinesia or kinesis (slow movement/no movement), and postural instability. Most people have primary, or idiopathic, disease. A few patients have secondary parkinsonian symptoms from conditions such as brain tumors and certain anti-psychotic drugs.

There is a little research on the causes of PD. Some assumptions are made, including issues such as severity of childhood abuse and neglect, as antecedent risks to the development of PD in adulthood. Mental factors and genes such as brain injury or a lack of serotonin is thought to be a part of the cause. (Cohen, et.al. 2001).

In Parkinson's Disease and Huntington's disease the nigra-striatum neural communication assemblage is severely hampered. PD results from a depletion in the amount of dopamine produced by the brain. At the onset of the disease, dopamine-secreting cells of the substania nigra, either because of genetic factors or environmental toxins, experience mass cell death. Thus, the nigra cells are unable to form synapses through which they secrete and relay dopamine to the striatum in a neural circuit within the basal ganglia (18).

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.

These deficits increase during the course of the disease and are due to loss of dopamine-secreting neurons in the motor circuits in the basal ganglia which are necessary for control and coordination of movements. The symptoms displayed because of this are: bradykinesia, resting tremor, rigidity of muscles and impaired posture (Millage, Vesey, Finkelstein, & Anheluk, 2017). Research indicates that exercise modalities can improve both motor and non-motor aspects of PD (Dashtipour et al., 2015).

PD pathology results from a degenerative process which reduces the function of dopaminergic substantia nigra (SN) neurons below a certain threshold until it manifests as clinical symptoms17. It should be noted that degeneration of the SN is not the sole location of degeneration – regions such as the locus coeruleus, raphe nuclei, basal forebrain, and frontal cortex undergo a similar process17. The pathology is still not fully understood, but the degenerative process has been found to stem from the glossopharyngeal, vagal, and olfactory cranial nerve nuclei and then ascend upwards through the brainstem18. The degeneration of these origin structures have been theorized to be responsible for the non-motor symptoms presented in PD18.

PD is clinical syndrome characterized by motor disturbance that will damage dopaminergic neurons. Also, PD induced by drug like dopamine antagonists and injure dopaminergic neurons by toxins. And it can be induced by other disease like progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy. Also, it could be genetic by mutation of gene encoding α-synuclein, Or by environment. Its pathological changes include that dopaminergic neurons incapable of producing dopamine.

Parkinson’s disease is affected by the degeneration of dopaminergic neurons which is responsible to produce dopamine. Dopaminergic neurons have their cell bodies in substantia nigra pars compacta (SNpc) in basal ganglia (O’Sullivan and Schmitz, 2007). Basal ganglia are a collection of interconnected gray matter nuclear masses deep within the brain”. These gray matter masses are caudate, putamen, globus pallidus, subthalamic nucleus and the substantia nigra. Basal ganglia receive its input through striatum (O’Sullivan and Schmitz, 2007).

for the treatment or prevention of PD but it will take more time and considerably more

PD is increasingly recognized as an extensive multi-system disease with widespread neurological impairment, affecting a variety of brain regions not directly involved in motor control. The extranigral pathology includes the olfactory bulb, the dorsal motor nucleus of the glossopharyngeal and vagal nerves, the intermediate reticular zone, subnuclei of the reticular formation and the raphe system, the locus coeruleus (LC), regions of the basal forebrain, many subnuclei of the thalamus and amygdala, and, in severe cases, the neocortex [64-67]. In 2003, Heiko Braak and colleagues [68] traced the course of the pathology in incidental PD cases and developed a staging procedure based on the location of α-synuclein-containing inclusion bodies, also

disorder that affects 10 million people worldwide. It is characterized by progressive loss of midbrain dopamine neurons in the substantia nigra pars compacta. Neither the molecular mechanism that underlies the pathogenesis of Parkinson’s is fully understood nor preventative and effective treatment is available. In the past few years, epigenetic mechanisms have emerged as potential mediators of environmental factors which cause abnormal epigenetic modifications which have been detected in PD. The term Epigenetics, refers to reversible heritable alterations in gene expression without any changes in DNA sequence. Fundamental mechanism of epigenetic regulation is mainly chromatin modification which is divided into several categories including DNA methylation, histone modification, histone variant, and non-coding RNA. This assignment discusses on recent studies on how epigenetic dysregulation, which modulates gene expression, plays key role in

A wide variety of dosing regimens are used to create the MPTP mouse model [155, 216-219]. In all cases, cell death is rapid with the first signs appearing within 12-72 hours and is maintained for several weeks [220]. Other hallmarks of PD observed include reductions in striatal DA and TH, elevated levels of acetylcholine, and reduced GSH [155, 221], as well as inflammatory markers and reactive gliosis [222, 223]. Mice administered MPTP display behavioral signs of decreased locomotor activity including akinesia and catalepsy [224]. The disadvantage of the MPTP model is that systemic MPTP lacks reproducibility in terms of behavioral changes and the degree of neurodegeneration. Many factors influence the reproducibility of the lesion, including

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,

Parkinson’s Disease or PD is a progressive disorder of the nervous system that affects movement. The cause of the disorder unknown, although many scientist believe that it is caused by both genetic and environmental factors. People who have first-degree relatives with PD have a four to nine percent higher chance of inheriting the disease.It has been suggested that PD may result from prolonged exposure to certain environmental toxins or injury. When someone has PD the neurons in their brain gradually break down or die.

C.1. Mouse PD model to be used in this project: In VMAT2 LO, a transgenic mouse PD model, shut-down of 95% endogenous vesicular monoamine transporter 2 (VMAT2) leads to a massive oxidative deamination of monoamine neurotransmitters [43], accompanied by increased oxidative stress markers and a significant decrease of antioxidant ability [44]. Therefore, oxidative damage could be the culprit for the replication of the pathogenic features of PD [45], including substantial reductions of DA and NE levels in the brain, progressive neurodegeneration in the SNpc and LC with formation of α–synuclein containing inclusions. More importantly, neuronal loss in the LC of VMAT2 LO mice starts earlier (at 12 months) and to a greater extent