Neethi Prem (2nd year PhD scholar) presented the progress on animal models of Schizophrenia
Dr Rukmani M R (1st year MPhil Scholar) presented a paper by Qian et al titled "Neuroprotection by the Soy Isoflavone, Genistein, via Inhibition of Mitochondria-Dependent Apoptosis Pathways and Reactive Oxygen Induced –NF - κB Activation in a Cerebral Ischemia Mouse" from the journal Neurochemistry International (2012).
Recently, the treatment of stroke has focused on antioxidant therapies, where oxidative stress is implicated The preventive and therapeutic potential of plant compounds on ischemic stroke has been intensively studied because many of them contain antioxidant properties. Genistein, one of the active ingredients in soybean, possesses many bioactivities. In this study, we investigated the potential neuroprotective effects of genistein and its possible mechanism of action in a cerebral ischemia mouse model Mice were pretreated with genistein (2.5, 5 and 10 mg/kg) or vehicle orally once daily for 14 consecutive days before transient middle cerebral artery occlusion was performed. Genistein at doses of 2.5—10 mg/kg significantly reduced the infarct volume. improved the neurological deficit and prevented cell apoptosis after ischemia. In addition. genistein pretreatment was shown to inhibit the ischemia-induced reactive oxygen species (ROS) production, enhance the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). and decrease levels of malondialdehyde (MDA) in stroke mice. Moreover, genistein reversed the mitochondrial dysfunction after ischemia. as evidenced by decreasing mitochondria ROS levels, preventing cytochrome C release to the cytoplasm and inhibiting caspase-3 activation. Western blotting showed ischemia activated the ROS-dependent nuclear factor-kB (NF-kB) signaling pathway, and genistein suppressed phosphorylation and activation of the NF-KE p65 subunit. as well as the phosphorylation and degradation of the inhibitor protein of kBa(IkBa). Our findings suggested that genistein has a neuroprotective effect in transient focal ischemia, which may involve regulation of mitochondria-dependent apoptosis pathways and suppression of ROS-induced NF-kB activation.
Vidyadhara D J (1st year PhD Scholar) presented a paper by Angot et al titled "Alpha-Synuclein Cell-to-Cell Transfer and Seeding in Grafted Dopaminergic Neurons In Vivo" from the journal PLOSone (2012).
Several people with Parkinson’s disease have been treated with intrastriatal grafts of fetal dopaminergic neurons. Following autopsy, 10-22 years after surgery, some of the grafted neurons contained Lewy bodies similar to those observed in the host brain. Numerous studies have attempted to explain these findings in cell and animal models. In cell culture. Alpha-synuclein has been found to transfer from one cell to another, via mechanisms that include exosomal transport and endocytosis, and in certain cases seed aggregation in the recipient cell. In animal models, transfer of alpha-synuclein from host brain cells to grafted neurons has been shown, but the reported frequency of the event has been relatively low and little is known about the underlying mechanisms as well as the fate of the transferred alpha-synuclein. We now demonstrate frequent transfer of alpha-synuclein from a rat brain engineered to overexpress human alpha-synuclein to grafted dopaminergic neurons. Further, we show that this model can be used to explore mechanisms underlying cell-to-cell transfer of alpha-synuclein. Thus, we present evidence both for the involvement of endocytosis in alpha-synuclein uptake in vivo. and for seeding of aggregation of endogenous alpha-synucleln in the recipient neuron by the transferred 2-synuclein. Finally, we show that, at least in a subset of the studied cells, the transmitted alpha-synuclein is sensitive to proteinase K. Our new model system could be used to test compounds that inhibit cell-to-cell transfer of alpha-synuclein and therefore might retard progression of Parkinson neuropathology.
Sunil Tripathi (1st year PhD scholar) presented a paper by Goshen etal 2011 "Dynamics of Retrieval Strategies for Remote Memories" from the journal Cell.
Prevailing theory suggests that long-term memories are encoded via a two-phase process requiring early involvement of the hippocampus followed by the neocortex. Contextual fear memories in rodents rely on the hippocampus immediately following training but are unaffected by hippocampal lesions or pharmacological inhibition weeks later. With fast optogenetic methods, we examine the real-time contribution of hippocampal CA1 excitatory neurons to remote memory and find that contextual fear memory recall, even weeks after training, can be reversibly abolished by temporally precise optogenetic inhibition of CA1. When this inhibition is extended to match the typical time course of pharmacological inhibition, remote hippocampus dependence converts to hippocampus independence, suggesting that long-term memory retrieval normally depends on the hippocampus but can adaptively shift to alternate structures. Further revealing the plasticity of mechanisms required for memory recall, we confirm the remote-timescale importance of the anterior cingulate cortex (ACC) and implicate CA1 in ACC recruitment for remote recall.
Dr Ghanshyam Pandey, Prof of Pharmacology from University of Illinois at Chicago gave a talk on "Neuroendocrine and Neuroimmune function in Depression and Suicide".
There are about 30,000 suicides per year in the US and is predominant among the young and geriatric (75+) populations. Suicide is a symptom rather than a disease and there are a number of risk factors such as depression, alcohol and drug abuse, early life trauma, family history, hopelessness, abnormal neurobiology, impulsive-aggressive behavior, conduct adjustment disorder, stress and contagion-copy cat cluster. The last few of these are predominantly seen in teenage populations which are also characterized by the fact that they are non-responsive to tricyclics but do respond to SSRIs.
Dr Pandey's group studied post mortem brain samples of depressed suicide victims and found that Protein and mRNA expression of Glucocorticoid receptors (GR) were lower in the prefrontal cortex(PFC) and amygdala. The same was true for Corticotropin Releasing Factor Receptor 1 (CRF-R1) and CRF Binding Proteins. Overall, dysregulation of the Hypothalamo-Pituitary-Adrenal (HPA) axis was seen to be related to altered expression of CRF and GR in PFC and amygdala. Interestingly, there was no change seen in the hippocampus. This could be because the sample population was young and perhaps the hippocampi had not yet been compromised.
In addition to the HPA axis, pro-inflammatory cytokines such as IL-1, IL-6, and INF-a were found to be increased and BDNF expression was decreased in depressed suicide victims.
Sumitha R (2nd year PhD scholar) presented her seminar on "Neuronal specification in spinal cord - Signals and Transcriptional codes".
She covered the role of BMP, Shh, Wnts, FGF and Retinoic acid in signaling and also how the concentration gradient of Class I (Pax, Dbx) and Class II genes (NKx family of transcription factors) determines whether a cell becomes a motor neuron or an interneuron.
Merlin P B (1st year MPhil Scholar) presented her seminar on 'Calcium in Neuronal signalling'.
The seminar was well structured and described the role of calcium at various levels of organization.
Some of the salient points were:
We watched and discussed most part of Charlie Rose Brain Series - Episode 2: "The Perceiving Brain". One controversial aspect was that surgery for squint (strabismus) correction may not be of benefit after a critical period. However see this article for a differing opinion. Overall, an excellent introduction to visual perception.
Ajay Kumar Nair (2nd year PhD scholar) presented his seminar on "Microstates - the atoms of thought? Studies in EEG, fMRI... A Conceptual Overview".
This seminar introduced a breadth of topics moving from cognition and consciousness to global workspace theory, cerebral networks, self organized criticality and scale free systems... and narrowed down to how the microstates approach to EEG analysis seems to provide evidence for the brain's function as a scale free phenomenon.