"Effect of a single dose of standard levodopa on cardiac autonomic function in Parkinson's disease" by SJ Sriranjini, Mohan Ganesan, Karuna Datta, Pramod Kumar Pal, Talakad N Sathyaprabha was published in Neurology India. Year : 2011  |  Volume : 59  |  Issue : 5  |  Page : 659-663

ABSTRACT
Background: Parkinson's disease (PD) is associated with autonomic dysfunction and chronic levodopa therapy has been reported to impair the autonomic control of heart rate. 

Aim: Our aim was to assess the immediate effect of a single dose of levodopa on heart rate variability (HRV) in idiopathic PD. 

Materials and Methods: Eleven patients of idiopathic PD (F:M =2:9, mean age 57.3±8.6 years, duration of illness 4.1±2.8 years, Hoehn and Yahr stage 2.1±0.2) on stable levodopa dosage were studied. Motor part of unified Parkinson's disease rating scale and resting Lead II electrocardiogram (ECG) recordings were performed at baseline (12 hours off medication) and after two tablets of 100/10 mg of standard levodopa/ carbidopa. ECG was recorded continuously in the first hour (H1) followed by a 15-min recording in second (H2), third (H3) and fourth (H4) hours. Artifact free 5-min segments of the ECG were analyzed offline to obtain the HRV parameters in time domain (ms) and frequency domains (ms 2 ). 

Results: Significant increase was observed in standard deviation of normal to normal intervals (23.5±2.7-46.2±6.6,P<0.05), root mean square of successive differences of NN intervals (16.3±2.9-30.7±5.1, P<0.01), total power (568.9±125.7-2739±667.5, P<0.01), low frequency power (146.5±40.8-614.1±206.7, P<0.05) and high frequency power (107.4±33.9-332.7±85.9, P<0.05) in H1. 

Conclusion: The results are suggestive of an improvement in the overall variability of the heart rate indicating an enhanced vagal tone.

Keywords: Cardiac autonomic dysfunction, levodopa, Parkinson′s disease

How to cite the article:
Sriranjini SJ, Ganesan M, Datta K, Pal PK, Sathyaprabha TN. Effect of a single dose of standard levodopa on cardiac autonomic function in Parkinson's disease. Neurol India 2011;59:659-63

Poojashri (1st year PhD Scholar) presented the paper by Foran etal in Glia (online since July, 2011) titled "Motor Neuron Impairment Mediated by a Sumoylated Fragment of the Glial Glutamate Transporter EAAT2".

KEYWORDS
amyotrophic lateral sclerosis; post-translational modification; SUMO; excitotoxicity

ABSTRACT
Dysregulation of glutamate handling ensuing down regulation of expression and activity levels of the astroglial gluta-mate transporter EAAT2 is implicated in excitotoxic degeneration of motor neurons in amyotrophic lateral sclerosis(ALS). We previously reported that EAAT2 (a.k.a. GLT-1) is cleaved by caspase-3 at its cytosolic carboxy-terminus domain. This cleavage results in impaired glutamate transport activity and generates a proteolytic fragment (CTE) that we found to be post-translationally conjugated by SUMO1. We show here that this sumoylated CTE fragment accumulates in the nucleus of spinal cord astrocytes of the SOD1-G93A mouse model of ALS at symptomatic stages of disease. Astrocytic expression of CTE, artificially tagged with SUMO1 (CTE-SUMO1) to mimic the native sumoylated fragment, recapitulates the nuclear accumulation pattern of the endogenous EAAT2-derived proteolytic fragment. Moreover, in a co-culture binary system, expression of CTE-SUMO1 in spinal cord astrocytes initiates extrinsic toxicity by inducing caspase-3 activation in motor neuron-derived NSC-34 cells or axonal growth impairment in primary motor neurons. Interestingly, prolonged nuclear accumulation of CTE-SUMO1 is intrinsically toxic to spinal cord astrocytes, although this gliotoxic effect of CTE-SUMO1 occurs later than the indirect, noncell autonomous toxic effect on motor neurons. As more evidence on the implication of SUMO substrates in neurodegenerative diseases emerges, our observations strongly suggest that the nuclear accumulation in spinal cord astrocytes of a sumoylated proteolytic fragment of the astroglial glutamate transporter EAAT2 could participate to the pathogenesis of ALS and suggest a novel, unconventional role for EAAT2 in motor neuron degeneration.

The paper was severely critiqued on several grounds. Some of the items that featured in the discussion include:
Technical

1. They talk about the nuclear localisation of carboxy terminus of EAAT2, through immunoflourescence studies, in-vitro and in-vivo in the form of puncta reported overlapping with the DAPI (nuclear) staining. However, the figures do not really support it; the intensity of EAAT2 (ABR556) fluorescence in the nucleus was too less to reach to an emphatic conclusion.
2. It was suggested that it would have been nice if along with/instead of staining isolated nuclei specifically, they could produce some electron microscopic images depicting the nuclear localisation of the CTE-SUMO1 fragment with the PML-NB.
3. In the third figure of the article they represent the localisation of EAAT2 in the nucleus of the transgenic (SOD1) astrocytes. However, the GFAP staining also seems to become more nuclear rather than cytoplasmic! Since GFAP is expressed pan-cytoplasmically in the glia and not in the nucleus, the results seem to be inappropriately extrapolated.
4. Experiments regarding the impairment of axonal growth convey little inference and way too much confidence; since in a culture, differentiating an axon among the neurites becomes an issue. 

Conceptual

1. The role of upregulated Netrin in adult astrocytes, as reported with their microarray and Q-real time PCR data, was strongly debated in the discussion.
2. While they report previously that SOD1 mutations trigger the caspase 3 activation that degrades EAAT2 in two fragments viz. truncated EAAT2 and Carboxy terminus of EAAT2- which is sumoylated and targetted to the PML- NB; the fact that SOD1 mutations are not the universal feature of ALS makes their conclusive linkage to a central pathogenic mechanism seem rather hasty. Perhaps autopsy studies on human spinal cord tissues would have validated their claim.
   

It was suggested that a summary of the lacunae be sent to the editor. 

Vijaya Kumar (1st Year MPhil Scholar) presented a detailed seminar on Thalamocortical organization.

He first discussed the different parts of the thalamus with focus on anatomy, afferents, efferents and functions of the dorsal thalamic nuclei. He then discussed the organization and connectivity of the different types of neurons in the various cortical layers. He explained how the pacemaker activity of the various neurons that are part of the thalamocortical circuits in burst and transmission mode are reflected during sleep and wake mode with special activity of the inhibitory reticular nuclei of the ventral thalamus.

The seminar stimulated an animated discussion on how the ARAS is involved during sleep and waking and in particular how the rhythmicity is maintained. 

References

• Kandel, Schwartz and Jessell (2000): Principles of Neural Science, 4th edition
  
• Dale Purves et al (2008): Neuroscience, 4th edition 
  
• Exploring thalamus – Sherman & Guillery.
  
• Functional Organization of Thalamocortical Relays –S.Murray sherman & R.W.Guillery, Journal of neurophysiology vol 76,1996.
  
• Medical physiology – Vernon Mountcastle 14th edition
  

As additional reading, the recommendations wGordon Shepherd's 'The Synaptic Organization of the Brain' was recommended as additional reading as well as some of the papers by M Steriade et al (such as: link).

Ajay Kumar Nair (1st Year PhD scholar) presented the paper "Use of swLORETA to localize the cortical sources of target- and distracter-elicited P300 components" by Bocquillon et al, Clinical Neurophysiology October 2011.

Abstract
Objective: Cognitive event-related potentials (especially P300) have long been used to explore attentional

processes. The aim of this study was to identify the cortical areas involved in P300 generation during a
selective attention task.

Methods: 128 channel electroencephalograms were recorded in 15 healthy controls performing a three-stimulus visual oddball paradigm, in order to identify distracter- and target-elicited P300 components. For each subject, the P300 sources were localized using standardized weighted low-resolution electro-magnetic tomography (swLORETA). One sample and paired T-tests were performed using SPM5.

Results: Common sources for both P300 components were observed within a large frontoparietal network, including the frontal eye field and dorsal parietal cortex (i.e. the attentional dorsal frontopari-etal network). More inferior parietal areas, prefrontal and cingulate cortices (i.e. the attentional ventral frontoparietal network) were also involved in the generation of target-elicited P300.

Conclusions: These results suggest that distracter- and target-elicited P300 are both generated by the
dorsal frontoparietal network. Moreover, target processing recruits a specific ventral network.

Significance: The data agrees with the literature reports using other methods and should help to improve our knowledge of the cerebral networks underlying attentional processes.

The paper provides a good literature review and methodological approach of this promising technique.