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Major psychiatric disorders Psychoses & affective disorders
Psychoses Disorders in which patients exhibit gross disturbances in their comprehension of reality as evidenced by false perception (hallucinations), false beliefs (delusions) and loss of contact with reality; schizophrenia most common form of psychosis (+ve n –ve symptoms)
Mostly concerned Abt –ve because poor prognosis , more difficult to treat, persist after positive symptoms have resolved
Mesolimbic Dopamine travels from the midbrain tegmental area to the nucleus accumbens. Increased activity in this pathway may cause delusions, hallucinations, and other so-called positive symptoms of schizophrenia.
Mesocortical pathways Decreased activity in the pathway that goes from the midbrain to the prefrontal lobe cortex can cause apathy, withdrawal, lack of motivation and pleasure, and other so-called negative symptoms of schizophrenia. Mesocortical dysfunction also disinhibits the mesolimbic pathway.
Nigrostriatal pathway from the substantia nigra to the striatum is involved in the coordination of body movements. Inhibition of this pathway causes the extrapyramidal side effects of antipsychotic drugs.
Tuberoinfundibular pathway from the hypothalamus to the pituitary inhibits the release of prolactin. Inhibition of this pathway leads to elevated serum prolactin levels.
2nd generation antipsychotics Clozapine, Risperidone, Olanazapine, Quetiapine, Ziprasidone, Aripiprazole (MOA, Dose, Brand name & A/E and receptor affinities)
Why do 1st gen. antipsychotics cause EPS & 2nd gen. do not? “Hit and run” hypothesis
Inflammation & schizophrenia
New drugs in pipeline Aspirin, Minocycline, Raloxifene, Estrogen, N-acetylcysteine (MOA and rationale of use)
Potential future targets of schizophrenia
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The neuroprotective role of glp1 receptor aganist in people with mood disorder
1. 1
The neuroprotective role of glp1 receptor agonist in people with mood disorder
The neuroprotective role of glp1 receptor aganist in people with mood disorder
Student Name
Department’s Name
University
dd/mm/yyyy
2. 2
The neuroprotective role of glp1 receptor agonist in people with mood disorder
Contents
Introduction ................................................................................................................................3
Glp-1 and Mood Disorder ...........................................................................................................3
How GLP-1 acts as a neuropositive for the treatments of the patients suffering from Mood
Disorders?...................................................................................................................................4
Conclusion..................................................................................................................................8
References ..................................................................................................................................8
3. 3
The neuroprotective role of glp1 receptor agonist in people with mood disorder
Introduction
The human body consists of a number of hormones. Each and every hormone has a different
function. Like many others group of hormones, ‘Incretins’ is a group of gastrointestinal hormone
which exists both in the periphery and also in the central nervous system of the human body. In
the recent times it has been found that this hormonal group has varies number of functions in the
human body which effects the structure and the functioning of the brain. The situations which are
related to mood disorders are associated with the brain and have similar alterations and
functions. The conditions which are related to mood disorders are as a result of the defects which
may reflect in the form of memory, learning and other execution function (Hlscher, 2011). Such
kind of defects are observed in a number of humans mainly who are having some or the other
kind of metabolic disorder. Also those patients who are suffering from the mood disorders have a
co-morbid metabolic conditions. This reports examines the role of GLP-1 receptor for the
treatment of people who are suffering from mood disorders.
Glp-1 and Mood Disorder
Mood disorder treatment in the patients by using various other methods for treatment also leads
to the number of abnormalities such as the gain the weight of the human body, the elevation in
the level of glucose in the body, the conditions related to hyperinsulinemia, resistance against
insulin and dyslipidemia (McIntyre et al, 2008). This was one of the most used treatments in the
past and were used for many mood disorder patients. However over the period of time, it was
observed that mood disorder is just not related to the brain and is also linked to a number of other
4. 4
The neuroprotective role of glp1 receptor agonist in people with mood disorder
symptoms such as the poor glucose homeostatic, resistance against the insulin and gain of
weight. Also, it was observed that GLP 1 receptors not only can be beneficial in diabetes but has
an impact in the growth of neurons in the body as well. According to the recent studies it was
also observed that many neuron related defects are caused due to the reduction in the active
Glucagon like Peptide (GLP-1) in the body (Ashrafian et al, 2013). It was found from the
experiments that the GLP-1 receptors are located in the brain and they also have a significant
effect on the human behavior. Recent evidences also suggested that it was the GLP-1 receptors
which have a significant role in a number of activities such as sleep patterns and other anti-
inflammatory and neuropositive activities. Also, it was found that it is the GLP-1 receptor which
helps in the reduction of the levels of Amyloid beta peptide and the oxidative damage in the
brain.
How GLP-1 acts as a neuropositive for the treatments of the patients
suffering from Mood Disorders?
It has been demonstrated that glucagon like peptide-1 (GLP-1) and its stable and lasting
analogues have been identified as the peptides which exerts the effects such as neuro-protective
and anti-apoptotic defects and the reduction of the beta-amyloid (AB) plague accumulation
(Greig et al, 2014). Also, it modulates the potentiation and synaptic plasticity for a long terms
and also helps in the promotion of the differentiation between the of the neuronal progenitor
cells. If we observe the similar behavior among the animals, the treatment by using the GLP-1
receptors has been demonstrated as a beneficial measure as it helps in the improvement of a
number of cognitive functions in the body such as the increase in the ability to learn and
5. 5
The neuroprotective role of glp1 receptor agonist in people with mood disorder
memorize the things and also have a good metabolism which also leads to the loss of weight and
the reduction of the risk for hypoglycemia (Calkin et al, 2013). The overall evaluation of the
effects of GLP1 Treatments in case of the mood disorder patients represents a number of
possibilities. There has been a number of evidences which supports the neuroprotective role of
the GLP-1 receptor and the stimulation of the same in the cells. Thus, the need for the review on
the GLP -1 for the treatment of mood disorders is increasing. This research is focused towards
the benefits of the treatment of mood disorders by GLP-1.
There are a number of neurological conditions in the mood disorders. This disorder is associated
with the motor function and the cognitive inability and also primarily caused as a result of the
selective neurological pathology which can often be said to derive from the different areas in the
human brain. In the recent times it has been observed that there has been a resemblance between
the metabolisms of AD brain and the relation of the same with T2DM (Numakawa et al , 2013).
The GLP-1 have a unique effect in brain and they help in the stimulation of the neuronal
proliferation. From the investigations it has also been observed that the increased level of a large
number of immune-historical methods which make the use of BrDu or the nuclear proteins. It has
also been observed that there has been a use of GLP-2 in the signaling event in the brain. These
signaling events are generated in the ciliary neurotic factor (CNTF) (Xu et al, 2013). The overall
administration of CNTF leads to the fact that there has been the observation of the induction
leading to the increase in the expression which is related to the face that there is a relation
between cell proliferationsand the GLP-1 signaling. Another proof related to the treatment of
mood disorders was observed by using GLP-1 with the cells in vitro there was an overall
observation that lead to the decrease in the level of Ki-67 stimulation (Vicknasingam et al,
6. 6
The neuroprotective role of glp1 receptor agonist in people with mood disorder
2013). This also proved that GLP-1 can be used for a number of treatments including the mood
disorders. Also the chronic treatment of mood disorders which was observed as a models by
experimenting on the rats gave rise to the conclusion that there was an increase in the progenitor
cell and also the increase in the DCX positive neurons (Bayliss et al ). A number of interesting
findings were also identified. Another beneficial feature which was observed with the use of
GLP-1 receptor was that there was an increase and the growth in the neurite outgrowths which
leads to pathway signaling. This was another benefit to the patients who are suffering from
various kinds of mood disorders. It has been observed that the treatment of the SH-SY5Y cells
in the human body has led to the increase in the number of cells who bear neurite (Darsalia et al,
2014). This is another benefit for the persons who suffers from the mood disorder. This disease is
normally caused due to the imbalance in the number of Chemicals which exists in the brain. The
use of GLP-1 receptor direct leads to the increase in the number of neurons in the brains and also
help in the increase in the number of cells which leads to the betterment of the patients who
suffers from mood disorders. Another benefit of using the GLP-1 receptor is the fact that it helps
in the incitation of the growth of the neurite.In order to have the cellular correlate for the purpose
of the memory formation, Long Term Potentiation (LTP) is used and this can also be identified
as the enhancement in the process related to the signal transmission in human brain (Bauer et al,
2014).This directly helps in the transmission of the information through neurons and helps for
the treatment of the people who are suffering with mood disorders (Chaldakov, 2014).
It has also been observed that under the normal circumstances, GLP-1 receptor can also be used
for the purpose of stimulation which leads to the promotion of LTP. This enhancement of LTP
also have a positive effect and on the stimulation of GLP-1R. The benefit of the LTP growth has
7. 7
The neuroprotective role of glp1 receptor agonist in people with mood disorder
a direct effect on the behavioral paradigms. It was observed on the rodents that the benefit of the
increase in LTP directly led to the improvement in the reference memory and also helped in the
better control (Sakr et al, 2013). Thus, there was an increase of the performance which led to an
associative and a spatial learning. A number of examples and demonstrations further gave an in-
depth view of the same and solidified the fact. The benefits which was observed by having the
treatment with GLP-1 stimulation at the cellular level can be easily found responsible for the
purpose of the enhancement in the process of learning and memory.
It was observed that GLP1 lead to the induced beneficial and psychological effects. Also it is
beneficial for the processes related to the cell proliferation. Also it is found to be benefitting in
the neural stem cell differentiation and the outgrowth of the neurite. The improved memory is
one of the most beneficial feature of using the GLP-1 receptor for the purpose of treatment of
mood disorder (Barb et al, 2006). The mood disorder is a disease which leads to a significant
enhancement in the physiological condition of the brain in case of the mood disorder.
A yet another benefit which was observed with the treatment using GLP -1 was the decrease in
the neuro-motor impairment. This GLP-1 receptor can significantly act for the patients who are
having neuropositive disorder (Shpakov et al, 2013). The mood disorder is caused due to the loss
of significant neurons or the imbalance in the same (Hutchinson et al, 2008). This leads to the
overall deficit in the motor function. It is the deficit of the motor function which forms the major
cause of the mood disorder (Marrinan et al, 2014). Also GLP-1 benefitted in the overall setting
of the mooddisorders. Some other experiments further led to the facts that GLP-1 also helped in
the overall settling of the human PD (Kaspar et al, 2013).
8. 8
The neuroprotective role of glp1 receptor agonist in people with mood disorder
A recent study has also led to the conclusion that there has been significant and more focused
benefits of having the GLP-1 activation in human brain (White et al, 2010). GLP-1 was also
observed to have an improvement in the reference memory performance and the decrease in the
overall duration of immobility in the body. Also, this was observed that there was an induced
hyper locomotion (Saez et al, 2012).
Conclusion
Mood disorders is one of the diseases whose actual cause wasn’t discovered for years. The cause
of the disease was based on the assumptions related to the chemical imbalances in the brain.
There hadn’t been a significant treatment of the disease before (Thein et al, 2011). But, in the
recent time a large amount of research has been done on the neuropositive response which is
generated from GLP-1 (Israili et al, 2011). It was been observed that GLP-1 receptor has a
significant effect on the brain and it is evident that it can be used as a significant hormone for the
treatment of the mood disorder patients (Foltynie et al, 2014). A large number of key
observations have been evaluated which has led to the conclusion that the GLP-1 have a
significant role and it exists as a neuroprotective in case of mood disorders (Ebdrup et al, 2012).
This has turned up as a successful treatment against the mood disorders and has turned up as a
new solution to the patients who are suffering from this disease.
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