Role Of Depression In Psychiatric Illnesses

This protein circulates throughout the central nervous system and the concentrations can be measured in platelets (Corripio, Gónzalez-Clemente, Jacobo, Silvia, Lluis, Joan, Assumpta, 2012). BDNF neurotrophins bind with high affinity to its respective receptor, TrkB. These signals flow to other protein enzymes downstream of that where they regulate synaptic functioning and maintain cell viability (Tadahiro, Richards, Shingo, Naoki, Miyako, Haruki, Xin, 2014). Studies performed on rats show a crucial link between BDNF release and memory/ cognitive functioning. After two months on an HFS diet (high amounts of refined sugars and fats) the hippocampal level of BDNF and spatial learning performance in these rats was noticeable reduced. Diet-related changes were specific to the hippocampus because of its role in memory formation and that is one of the main places BDNF is produced and circulates (Molteni, Barnard, Ying, Roberts, Gómez-Pinilla, 2002). These decreased cognitive functions cooresponded to a decreased amount of BDNF measured in the blood stream. It is also well documented through research that BDNF protects neurons from degeneration due to the cascade of effects it has on other proteins and enzymes when it is released. Therefore, the reductions of BDNF that are seen resulting from an HSF diet may decrease a neurons ability to natural protect itself from degeneration (Molteni, et al., 2002). Inversely, an increased amount of serum BDNF circulating in

During normal development of the mammalian central nervous system (CNS), neural stem cells (NSC) give rise to neurons via process of neurogenesis (Kempermann et al., 2004; Zhao et al., 2008). Neurogenesis normally occurs in dentate gyrus (DG) region of the hippocampus and lateral ventricle of sub-ventricular zone (SVZ) (Zhao et al., 2008). Hippocampal neurogenesis plays pivotal role in neurologic and psychiatric disorder like epilepsy, depression, schizophrenia and mood disorders (Antonova et al., 2004; Keller and Roberts, 2008; Lucassen et al., 2006; Zhao et al., 2008). Development of the nervous system is complex, and includes multistep dynamic processes such as proliferation, differentiation, migration, expansion of axons and dendrites, synapse formation, myelination and programmed cell death (Rice and Barone, 2000). These processes required the coordinated expression of cellular and molecular events in a spatial and temporal manner during the brain development (Rice and Barone, 2000; Rodier, 1994). Several growth factors and signal transduction cascades have been implicated in controlling NSC behavior in the developing brain (Faigle and Song, 2013). Among these, members of the Wnt family of secreted glycoprotein thought to be variably influence proliferation and lineage decisions of NSC and their progeny (Clevers et al., 2014).

Long-term potentiation refers to the steady increase in synaptic activity between two neurons which causes persistent strengthening of synaptic activity. Since memory formation is mainly dependent on synaptic strength, LTP seems to play an essential role in memory formation. Contrary to that, long-term depression causes a reduction in synaptic activity between two neurons, causing a decrease in synaptic activity. LTP and LTD are essential for normal functioning of the brain and balance in the ratio of LTP/LTD is needed for homeostasis. The levels and activity of LTP and LTD are majorly dependent on Calcium levels, Calcium-Calmodulin Kinase, NMDARs (N-Methyl-D-Aspartate receptors) and AMPARs (α-amino-3-hydroxy-5-methylisoxazole-4-propionic

There has been a myriad of research investigating the symbiotic relationship between hippocampal volume and major mood disorders (MDD) like depression. Despite being one of the most prevalent illnesses, the underlying pathogenesis and neurobiology of MDD remain unclear. It has been widely documented that patients with a MDD tend to have smaller hippocampal volumes (Sheline et al., 1996, Nordanskog et al., 2014). The hippocampus is known to be closely affiliated with the hypothalamic-pituitary-adrenal axis, which is required to produce glucocorticoids that are involved in stress mechanisms (Chen et al., 2010). Moreover, stressful life events are considered a critical risk factor in the development of depression (Zannas et al., 2013). This, coupled with findings which suggest that depressed patients have difficulty with hippocampal-dependent learning and memory tasks (Gould et al., 1998, Gould et al., 2007), accentuates the relationship between the hippocampus and MDD being mediated through stress. There are various hypotheses regarding what may cause hippocampal volume diminution as a consequence of stress. Major propositions involve hippocampal neurogenesis in the dentate gyrus (Becker and Wojtowicz, 2007), glial numbers, apoptosis (Czeh and Lucassen, 2007) and granule neuron numbers (Boldrini et al., 2013). Other mechanisms that may affect hippocampal volume like neuropil reduction, shifts in fluid balance between the ventricles and brain tissue and changes in

(Ernst, Olson, Pinel, Lam, & Christie, 2006), investigated, antidepressant effects of exercise: Adult neurogenesis refers to the growth of new neurons in the adult brain, initially reports of adult neurogenesis were viewed with a great deal of skepticism, because neurogenic activity had been assumed to be limited to the developmental period; however, the legitimacy of adult neurogenesis in some brain areas has since gained wide acceptance. It is now clear that some regions of the adult mammalian brain contain populations of active progenitor cells that can give rise to new neurons and glia cells. It has been hypothesized that a decrease in the synthesis of new neurons in the adult hippocampus might be linked to major depressive disorder (MDD).

The hippocampus is smaller in patients with depression. The smaller hippocampus is thought to be diminished because of a persistent exposure to stress hormones, like cortisol, which impacts the growth of nerve cells. The hippocampus is highly susceptible to stress, perhaps because the protracted ontogeny or the high amount of glucocorticoid receptors (Uma Rao et al.; 2010). The longer the patient has depression, or the more episodes of depression the patient experiences, the smaller the hippocampal volumes become. Stress correlates with the smaller hippocampus, researchers used twenty-nine patients with depression, twenty-two patients with severe depression and thirty-two control patients. All patients were around the same age, physically healthy, alcohol and drug free, and did not have any other kind of mental illness like bi-polar disorder, autism, or schizophrenia. Structural imagery was used to obtain the images of each patients’ entire brain. Then an image was aligned with the anterior commissure and posterior commissure as well as the borders of the left and right hippocampus. From the MRI scans and using a formula the hippocampal volumes were figured. All of the patients were followed up on, every 6-months for up to five years. The results were conclusive, the severely depressed and the depressed patients had smaller hippocampal volumes when compared to the control subjects. The left hippocampus of the patients was smaller by 4.9% and 4.2%, respectively, while the

In spite of many studies on animals and human subjects, the mechanisms that promote neuroplasticity

Neurotransmitters are chemical messengers that carry messages between neurons and affect behaviour, mood and thought. Two of the neurotransmitters that play a role in depression are norepinephrine and serotonin (Shives 2005). In depression, neurons don’t produce enough neurotransmitters. Shives (2005) states as a result, membrane channels don’t open, nerve messages are not communicated, and areas of the brain affecting emotion may not receive stimulation (Shives 2005). The hormonal system known as the hypothalamic-pituitary-adrenal axis, that regulates the body’s response to stress, is overactive in many people with depression. The hypothalamus increases production of corticotrophin releasing factor when a person’s physical or psychological well-being is threatened (Shives 2005). Elevated levels of corticotrophin releasing factor lean to an increase in hormone secretion by the piturity and adrenal glands which prepares the body for defensive action (Shives 2005). The chronic overactivity of the hypothalamic-pituitary-adrenal axis may occur following a traumatic experience this may contribute to the onset of depression (Shives 2005).

A deficiency in both serotonin and norepinephrine neurotransmitters specifically in the locus coeruleus, and the dorsal raphe nucleus, which both are important in relations to serotonin receptors can cause depression in AD. Individuals who had both AD and depression showed fewer neurons in the two locations when compared to non-demented individuals (Modrego, 2010 as cited by Zubenk, Moossy & Knopp, 1990). The use of animal shows the links of depressive behavior and AD. Ledo et al. (2016) used a mouse model to show an association of amyloid beta oligomers (AβOs) and depressive like behavior. It was hypothesized that AβOs induced depressive behavior in AD by causing an inflammatory response, which was triggered by activation of microglial cells. Ledo et al. (2016) found that AβOs decreased serotonin levels in the mice. This suggest that the decrease levels in the brains are leading to abnormalities in the AβOs, which then causes cognitive impairments.

Two structural proteins, synaptophysin (hereafter: SYP) and microtubule-associated protein 2 (hereafter: MAP-2), which are implicated in neuronal plasticity, were chosen as molecular targets. The underlying reason was to ascertain whether or not gestational stress modifies the expression of the proteins, SYP and MAP-2, in the rat’s hippocampus. If it indeed does, then subsequent monitoring of the recovery process of the stress-induced changes in control and treatment groups would be of prime importance so as to discern and comprehend the roles of these two proteins pertaining the actions of gestational stress administration of

Integration of disciplines is essential for developing new approaches to treat mental health disorders. Identifying key players in the underlying pathology of schizophrenia, bipolar, and depressive disorders will prove new targets for treatments. In the past, glial cells have been overlooked in the treatment of schizophrenia, bipolar, and depressive disorders. Now, with new technology, the class of neuroglia, called astrocytes, has been implicated in the underlying pathology of these disorders. The question that emerges is: How does new research on neuroglia affect development of new treatments for psychopathologies?

The amygdala is a critical substrate or a pair of critical nuclei within the subcortical limbic system regulating emotion- and mood-related behaviors. Further, the nerves connected with multiples of other structures involved in stress responses, including, the prefrontal cortex (PFC), the mesolimbic reward pathway and the hippocampus. The amygdala activates the natural flight or fights to escape from dangerous situations, learning to fear and not to fear, creating memories of fear and safety. According to ….. Studies show that numerous structural and functional neuroimaging methods have revealed activity-dependent adjustment of the amygdalae for hyperactivity and hypertrophy in patients with psychiatric illness. Similarly, the current study in rodents shows that three hours per day of restraint stress for 14 days cause mice to show long-term depressive behaviors, manifested by disrupting sociality and despair levels of extracellular glutamate. And that chronic restraint stress-provoked hypertrophy of BLA neurons can be reversed by lithium treatment; implying that stress-related abnormal remodeling of BLA neurites can be medically reversed in chronic stress-related disorders. These behavioral changes communicated with

Niwa et al. showed that knockdown of DISC1 during in the pre and perinatal stages alters neuronal maturation and attenuates prepulse inhibition and responses to methamphetamine. The in utero electroporation can only affect neurons at the time of electroporation thereby has limited temporal control. Our approach will be able to influence neuronal populations generated throughout the whole embryonic period. Similar to our approach, Greenhill et al. used dox-inducible system to express c-terminal fragment of DISC1 from P7 to P9 in neurons and found deficit of long-term potentiation (LTP) in their model [80]. Our Nes-DN-DISC1 mice show changes in anxious and depression behaviors, which are consistent with recent genetic finding of an association of DISC1 with MDD [60]. Moreover, our results together with other studies [81] suggest that the interaction of genetic risks with environmental triggers may be needed to elicit more severe psychiatric symptoms.

Adult neurogenesis involves persistent proliferative neuroprogenitor populations that reside within distinct regions of the adult brain. This phenomenon was first described over 50 years ago and it is now firmly established that new neurons are continually generated in distinct regions of the adult brain. The potential of the neurogenesis process lies in improved brain cognition and neuronal plasticity particularly in the context of neuronal injury, neurodegenerative disorders. In addition, adult neurogenesis might also play a role in mood and affective disorders. The factors that regulate adult neurogenesis have been broadly studied; however, the underlying molecular mechanisms of regulating neurogenesis are still not fully defined. Here we discuss the current understanding of these factors and provide a critical analysis of the molecular

Hensler (2002) demonstrated in rats that were chronically injected (ip) with FLX showed a decrease 5-HT1A expression in the raphe nuclei. Further, 5-HT2B receptors have been shown to be involved in brain development (Lin et al., 2004) particularly in migrating cranial neural crest cells in the mouse (Choi et al., 1997). Moiseiwitsh and Lauder (1995) also showed that 5-HT has a dose-dependent effect on cranial neural crest migration, suggesting that neural crest migration is disrupted at high concentrations. Silva et al. (2010) demonstrated that postnatal FLX treatment in rats decreased the number of serotonin and serotonergic terminals in the dorsal raphe nuclei; suggesting neuroplasticity dysfunction causes impaired development of the serotonergic system.