Multiple Sclerosis and Autism Spectrum Disorder Causes

Multiple induration and Autism Spectrum Disorder CausesMultiple sclerosis and Autism spectrum put out argon two neurophysiological unsoundnesss that atomic number 18 found to develop in the catchingally unvaccinated population. The shoot starts of these diseases and the exact interplay between the brokertic factors and environmental factors in the maturation of the disease atomic number 18 serving to be a billion dollar question. sixfold SCLEROSISSymptoms and ProgressionMS is a chronic neurologic tick which affects the central nervous agreement (CNS).1 The CNS consists of the read/write head, ocular nerves and the spinal cord. As the CNS controls various motor and demeanoral functions in the body, an force of symptoms develops. The symptoms as advantageously as the progression of the disease varies substantively from undivided to single(a). The symptoms in to the highest degree individuals though, start at the age of 20 to 40, further the symptoms argon unfe ignedly slight that they usually go un noniced savings bank the disease progresses. In few individuals, the symptoms are noticeable right at the onset of the disease it self.2SYMPTOMSVISUAL IMPAIRMENT As the disease attacks the optic nerves, visual problems arise in the patients. The inflammation of the optic nerves head teacher to severe pain behind the eyes. Double vision is a actually common symptom in MS patients. In certain patients, chargetide vision loss is reported.BLADDER AND BOWEL PROBLEMS 50% of the patients have constipation which sometimes lead to faecal impaction. Bladder problems arise which makes the patient to have more frequently.COGNITIVE SYMPTOMS Hearing balk, loss of memory or swindle term memory loss, slurred speech, attention troubles. Dizziness and depression are reported as well.MOTOR SYMPTOMS Numbness, tremor, gait, muscle spasms and seizures, fatigue and vertigo.SEXUAL DYSFUNCTIONS Males bear upon by MS have difficulty in getting / maintaining an erection. Females touch by MS have difficulty in getting orgasms.2 bankruptment OF DISEASEThe progression of disease, further like the symptoms, deviate from one individual to another. There are five types of progression seen in MS patients.Relapsing-remitting MS Majority of patients orient this kind of progression. As the name suggests, there are episodes of mild/severe symptoms followed by episodes of very mild or no symptoms at all. The episode of attacks usually lasts between few hours to a few monthsPrimary advancing MS About 10-15% of the patients have primary progressive MS. The severity of the symptoms worsen progressively. No backsliding and remission cycle is seen in these patients.Secondary progressive MS The initial stages of the disease show relapse and remission cycles. just after a certain point, the symptoms worsen gradually, just like in the primary progressive MS.Progressive relaxing MS In these patients, the symptoms are followed by recovery, but the se verity of the symptoms increase gradually. gracious MS The individuals undergoes episodes of mild symptoms but gets recovered completely ergo no permanent disability.3GENETIC FACTORSThe exploreers have identified certain agents and environmental factors which most likely cause and progress the disease. One striking observation is that contractable linkage studies have shown the variation in the genes associated with the Major Histocompatibility complicated (MHC) promotes the gamble of exposure for developing MS in individuals.4 The group of genes called the human leukocyte antigen (HLA) genes encodes for Major histocompatibility hard (MHC) in our body.5 The HLA genes are usher in the short arm of chromosome no 6. The MHC consists of two classes. The genes HLA-A, HLA-B and HLA-C form the MHC class I. The genes HLA-DP, HLA-DQ and HLA-DR make up the MHC class II. The MHC proteins stick to to the T- stalls to recognize antigens.6So, the MHC basically helps the immune system to differentiate between self and non-self cells (a property called as MHC restriction).6 It has been identified that the HLA-DRB1 mutant alleles and HLA-A alleles increases the risk of developing the disease.7,8 though these are the most commonly reported variant gene premise in MS, variants in genes set out in the HLA system such as HLA-DR15, HLA- DQ6,etc have been link to the disease as well.7Also, variants in IL7R have been linked to MS. Presence of C risk allele of the IL7R gene decreases the appearance of IL7R.9 IL7 signalling passageway is of the essence(p) for the T cell differentiation of CD4-CD8- thymocytes.10It also plays a major(ip) berth in maintaining the T-cell homeostasis. Variant of the IL7R results in the decrease in the expression of IL7R which affects the interlukin pathway, thereby disrupting the T cell development and T cell homeostasis.10But with the help of genome wide association studies (GWAS), a set of 12 susceptible genes which promotes the risk for d eveloping MS have been identified recently.11,12,13 Although the effect of variations in these genes are not as profound as the variations in the HLA gene system.11De myelinationThe neuron/nerve cells comprises of a cell body and an extension from the cell body called axon. The axons play a central role in carrying the communicate from one neuron to another. The axons in the body usually have a finishing rich in lipids, called the myelin. Myelin insulates the axon and protects it (just like an insulating coating over an electrical wire).14This helps in the efficient nerve transmission. Myelin present in the central nervous system are amazed by a special set of cells called the oligodendrocytes.15It is believe that in MS patients, a intractable immune system is unable to differentiate between the self and non-self cells and cause an inflammatory reply, most likely because of the variations present in the HLA gene system and IL7. This triggers the T-cells to attack and destroy th e myelin sheath of the axon or the oligodendrocytes (cells that produce the myelin sheath), keeping the nerve fibres unprotected and uninsulated. This is called as demyelination.14This consequently causes ending to the nerve fibre (as the protective sheath is degenerated). This produces many scar tissues or lesions (hence the name fivefold sclerosis) along the nerve cells, thereby limiting or blocking the transmission of impulses through the nerve cells. Consequently, the brain cannot communicate decent with the other parts of the CNS and eventually causes the various symptoms that are seen in the MS patients. In a nut shell, the disease is believed to be caused by the interplay between inflammation and neurodegeneration.1 After the episode of attack, the inflammation reaction may get halted and the neurons that are not demyelinated resume their normal function and even some recovery is possible (as seen in the relapsing-remitting type of progression). It has also been shown tha t the demyelinated axons range to produce more sodium impart and this helps in the remission.16 So, sodium impart are rightfully targeted for the MS therapy now.17 Also, even though the oligodendrocytes are not present around to remylinate immediately, myelin does grow back, but it may give in a real long time.15Picture Source eMedicineHealth, (2014).Myelin and the Central uneasy agreement Causes, Symptoms, Treatment What is myelin? eMedicineHealth. online obtainable at http//www.emedicinehealth.com/myelin_and_the_central_nervous_system/page2_em.htmAUTISM SPECTRUM DISORDERAutism spectrum disorder (ASD) is a neurodevelopmental disorder that causes kindly, cognitive and language impairment and the tendency to show exigent behaviour, interests and activities in the individuals.18 ASD is a collection of neurodevelopmental disorder.19The main types of ASD are Autism, Aspergers syndrome, Pervasive developmental disorder- not otherwise specified (PDD-NOS). The rare disorders in th e class are Rett syndrome and Childhood disintegrative disorder.18Symptoms and ProgressionSymptoms include impairment of social relationships, lack of communication and lack of imagination skills and signs of repetitive behaviour. Symptoms vary from one individual to another significantly. 18Aspergers syndrome patients did not have significant cognitive impairment/delays like autism patients. PDD-NOS is considered as the milder form of sick behaviour and usually show symptoms in one area, for instance, just lack of social communication.19 The progression of the disease is also different in different patients. Symptoms in childhood may include constant crying, sleeping problems, absence of speech, repetitive movements like handshake or clapping, lack of eye contact, etc. Symptoms in the adolescence and adulthood may be mood imbalance, presence of disability becomes more obvious and prominent, increased anxiety levels, epilepsy and seizures in rare cases.19Genetic factorsADS is more of a syndrome than a disease, caused by a variety of transmittable and environmental factors.19 Whole genome screens, next generation sequencing (NGS) and cytogenetic studies have been carried out to normal out the genes obscure in the cause of the syndrome.20 ADS is a really complex neurological condition which is linked to about 100 genes as of now. 21The genes broadly fall intogenes regulating synapsisgenes regulating transcriptionMutation of genes that are involved in the synaptic functions are commonly observed in ASD. A few important genes are discussed belowNeurexin (NLGN3, NLGN4) and Neuroligin (NRXN1)The genes involved in the return of Neurexin and neuregulin are commonly found mutated genes in ASD. Neurexin and Neuregulin act as neural cell surface receptors and organize the interaction between the pre-synaptic and post-synaptic neurons. Neurexin interacts with CASK in the pre-synaptic neuron. Neuroligin interact with PSD95 in the post- synaptic neuron. The two prote ins interacts with intracellular factors as well as scaffolding protein, forming a trans-synaptic interaction necessary for a synapsis to exist. Mutations in the genes encoding for these proteins have been reported in ASD patients. Also, the targeted knock out of these genes in the mouse model have caused deregulation of synaptic function. Mutation of neurexin in mice have shown to disrupt the voltage-gated calcium channel, thereby hindering pre-synaptic set down of vesicles. Mutations in neuroligin in ASD patients reduced the expression of neroligin, thereby causing less interaction with neurexin thereby causing synaptic transmission defects.22SHANKSHANK consists of trinity genes SHANK1, SHANK2, SHANK3. SHANK is involved in the post-synaptic neuron. It interacts with PSD95 and SAPAP and form a protein complex which regulates the institution of dendritic acantha. Overexpression of SHANK3 results in the increase in the dendritic spine and the collective results in the decrease o f dendritic spine formation. Reduced dendritic spine formation leads to defective postsynaptic structure thereby inhibiting synaptic transmission.22Also, sports in cadherin9, cadherin10 and cadherin15 are observed in ADS patients. Mutations in these genes destabilize the pre-synaptic and post-synaptic interactions, thereby inhibiting synapsis, leading to autistic symptoms.22Contactin associated protein-like 2 (CNTNAP2)CNTNAP2 is a member of the neurexin family that encodes for a neuronal membrane protein that helps in the trans-synaptic interaction. Mutations in this gene have been reported in autistic patients.20MECP2 geneMethyl cytosine binding protein (MECP2), a transcriptional regulator, is mutated in Rett syndrome. The gene is present in the X chromosome. This vicissitude occurs exclusively in females as the mutation of this gene in males is lethal. Mutation of this gene results in leads to reduced release of vesicles in inhibitory synapsis and affecting the excitation to inh ibition ration. 23Another rare mutation in the form of the transcriptional regulator, ARX, is seen in autistic patients.23Picutre Source Walsh, C., Morrow, E. and Rubenstein, J. (2008). Autism and Brain Development.Cell, 135(3), pp.396-400. bureau of demyelination in the diseaseMutations in HLA region (like MS) and increased level of IL12 are reported in autism.24 This causes the T cells to attack the myelin sheath. The damage of myelin sheath ergo nerve cells (mechanism explained above) have been a factor of brain damage in autistic individuals. Neuropathological findings suggest a role for demyelination in the damage of amygdala, hippocampus and cerebellum of autistic patients.24Environmental factorsAlong with the genetic factors, the environmental factors also seem to play a role in the development and progression of these two diseases. Lack of Vitamin D supposedly plays a role in increasing the risk of developing MS.2 Mercury vaccines have been guess to increase the risk of dev eloping ASD.25 Mercury vaccine results in the want of zinc and that in turn impacts the level of vitamin B12.25 Vitamin B12 in turn is essential for myelin sheath formation.25In sum, these two neurological diseases are really complex and not yet fully understood yet. Tonnes of research are being performed in order to understand the cause and the exact interplay of genetic factors in the development of disease. Fully understanding the diseases would also provide better ways to treat individuals affected by these devastating complex neurological diseases.REFERENCESMcDonald WI, Ron MA. 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