Biodata name of the Nominee : Birendra Nath Mallick 2
SCOPUS CITATION ANALYSIS (66 PAPERS)
Yüklə 175,31 Kb.
|
SCOPUS CITATION ANALYSIS (66 PAPERS) Key words : Mallick, B., School of Life Sciences, Jawaharlal Nehru University, New Delhi, India Citations <2010 2010 2011 2012 (up to Nov)
h index = 20 B. Book chapters : 1. Mohan Kumar,V., Chhina,G.S., Mallick,B.N., Datta,S., Bagga,N. and Singh,B., Preoptic area in sleep-wakefulness. In: Motivational and emotional stress. Ed: K.V.Sudakov, USSR Academy of Medical Sciences, 1984, p. 67-76.
5. Mallick, B. N., Can yoga help improve sleep loss related problems? Proceedings of the World Householders' Yoga: Conference on sane living, Dec 25-26, 1997, Bombay, India 1997, pp. 85-88.
C. Book Review : Book Name : The Golden Age of Rapid Eye Movement Sleep Discoveries 1965-1966; by Claude Gottesmann, Nova, New York, 2005. Published in Sleep and Hypnosis Sleep and Hypnosis, 8 (2006) 71 - 72. D. Books edited/written : 1. Mallick, B. N. and Singh, R. (1994) Environment and Physiology, New Delhi. Narosa Publishing House, 278 p.
public). 4. Mallick, B. N., Pandi-Perumal, S. R., McCarley, R.W. and Morrison, A. R. (2011) Rapid Eye Movement Sleep : Regulation and Function, Cambridge University Press, London, United Kingdom, 478 p.
'Homology Modeling of Alpha1A-Adrenoreceptor ' RCSB ID : rcsb 035534; PDB ID : code 2F75 Vijayan, R., Subbarao, N. and Mallick B. N.
“Homology Modeling of Beta-1 Adrenergic Receptor” RCSB ID : rcsb; PDB ID : code 2FF9 Vijayan, R., Subbarao, N. and Mallick B. N. F. Patent Information : Title of invention : A Method for diagnosis of REM Sleep loss by blood protein estimation. Patent No. : 7,125,724 Issue Date of Patent : Oct 24, 2006
Rapid Eye Movement (REM) sleep is a unique phenomenon expressed during sleep and was objectively identified based on electrophysiological characteristic signals recorded from the scalp, eyes and neck muscles. It is present through evolution in the higher mammals and continues through life although the quantity may vary. Loss and/or disturbance in this stage of sleep are associated with several somatic, psychic, developmental and other disorders, however, the mechanism of its regulation, function and mode of action(s) were unknown, which are the focus of Biren Mallick’s study. In brief, his studies may broadly be described under Neuro-anatomical and neurochemical mechanism of regulation of REM sleep and Functions of REM sleep which have been discussed below under four heads (A-D). A) Mechanism of Neural Regulation of Rapid Eye Movement Sleep Generation : a) Cessation of activity of REM-OFF neurons in the locus coeruleus (LC) is a pre-requisite for REM sleep generation (reviewed Pal et al., 2005; Pal and Mallick, 2007) : Before he started independent work at School of Life Sciences, Jawaharlal Nehru University (SLS/JNU), it was known that there are cholinergic REM-ON and noradrenaline (NA)-ergic REM-OFF neurons in the brain stem and they are likely to be reciprocally connected for the regulation of REM sleep. Since the REM-OFF neurons are continuously active all through except during REM sleep, he proposed that cessation of those neurons may be a pre-requisite for the generation of REM sleep. Therefore, he hypothesized that if those REM-OFF neurons were continuously kept active (i.e. they were not allowed to cease activity), REM sleep should not be generated or at least significantly reduced. To prove, under surgical anaesthesia electrodes were implanted for sleep-waking recording and stimulation of locus coeruleus (LC). After recovery, in freely moving normally behaving rats it was indeed found that upon continuous activation of the LC neurons by mild, low frequency electrical stimulation, there was significant reduction in REM sleep, which was followed by a rebound increase in REM sleep after the stimulation was stopped confirming my hypothesis (Singh and Mallick, 1996). b) Mechanism of cessation of REM-OFF neurons in LC : Until mid 1980s based on isolated independent studies existence of reciprocal relationship (when one neuron is active the other remains inactive) between REM-OFF and REM-ON neurons was proposed for effective regulation of REM sleep; however the neurochemical nature of such action was unknown. i) Simultaneous recording of REM-OFF and REM-ON neurons : In JNU, Biren Mallick initiated and established the facility to maintain animals higher than rats, the cats. He then successfully established (technique) recording single neuronal activity in freely moving normally behaving cats. His are the first publications from this country based on single neuronal activity recorded from freely moving animals. Unlike earlier isolated studies, by simultaneous recording of a pair of REM-OFF and REM-ON neurons in freely moving cats, his group showed for the first time that those neurons are reciprocally active in relation to REM sleep and waking (Mallick et al., 1998). ii) Mechanism of inhibition of REM-OFF neurons for REM sleep regulation : The REM-OFF neurons must stop, while the REM-ON neurons increase firing during REM sleep; however, their neuro-chemical nature for inducing such behaviour was unknown. The group led by Biren Mallick proposed that cholinergic input from REM-ON neurons is likely to excite inhibitory GABA-ergic neurons which in turn would inhibit the REM-OFF neurons for REM sleep generation. They carried out studies in surgically prepared chronic freely moving rats having electrodes for recording sleep-waking patterns and indwelling cannulae to microinject receptor agonist and antagonist into the LC. They used single and sequential microinjection of chemicals in various combinations; the latter technique was first used by Mallick (Mallick and Alam, 1992). Their findings confirmed that REM-ON cholinergic output excites the GABA-ergic neurons which inhibit the REM-OFF neurons inducing REM sleep (Mallick et al., 2001). Thus, Mallick’s group put forward GABA-interneuron model (Mallick et al., 2001), which revised the earlier models for REM sleep regulation. This is a significant advancement to our understanding on neurochemical basis of REM sleep regulation (Fig. 1). Subsequently, combining stimulation of prepossitus hypoglossi (PrH) and simultaneous blocking GABA action by picrotoxin into the LC, they proposed that REM-ON cholinergic inputs may also excite PrH GABA-ergic neurons, which may also contribute (in addition to the GABA-ergic interneurons in the LC) towards inhibition of the REM-OFF neurons for REM sleep regulation (Kaur et al., 2001).
Thereafter, they investigated role of NA (possibly from LC REM-OFF neurons) on PPT REM-ON neurons in the above model (Fig. 1) for REM sleep regulation. Using sequential double microinjection of adrenergic agonist and antagonist along with GABA-ergic antagonist into the PPT, they confirmed interaction of adrenergic and GABA-ergic inputs on the PPT REM-ON neurons for the regulation of REM sleep (Pal and Mallick, 2006). Subsequently they found that GABA-terminals from substantia nigra possibly acted pre-synaptically on the NA-ergic terminals in PPT and modulated NA-release on the REM-ON neurons to regulate REM sleep (Pal and Mallick, 2009) as summarised in Fig 2. Fig. 2 
d) Mechanism of action of brainstem Sleep and Waking areas in modulating REM sleep : REM sleep normally follows deep sleep, it does not follow wakefulness and it may end either into slow sleep or in waking; although these patterns may not hold in disease e.g. narcolepsy. However, the cellular mechanism for such expression of REM sleep was lacking. Therefore, Mallick proposed that :
Cats were surgically prepared having implanted electrodes for recording behavioural sleep-waking, single neuronal activities and for inducing sleep or waking at will by stimulation of deep brain areas. After recovery, the recordings were carried out in freely moving normally behaving conditions. REM-ON and REM-OFF neurons were recorded and their responses were studied upon stimulation of physiologically confirmed deep brainstem areas, the midbrain reticular wakefulness inducing area and caudal brainstem reticular formation sleep inducing area. It was observed that the wakefulness inducing area excited the REM-OFF neurons and inhibited the REM-ON neurons (Thankachan et al., 2001) (Fig. 3); while the sleep inducing area largely had opposite influence (Mallick et al. 2004). Fig. 3 
Based on these results the following working model has been proposed (Mallick et al. 2004) for the neural regulation of REM sleep (Fig. 4).
Fig. 4 (Book chapter Mallick et al., 2006) 
e) Physiological verification of the proposed model : As mentioned above, GABA inhibits the REM-OFF neurons in the LC for REM sleep generation (reviewed Pal et al., 2005; Pal and Mallick, 2007). For physiological confirmation, it was proposed that if the model was correct, then if GABA-blocker was intermittently infused into the LC for prolonged period (several days), the LC-REM-OFF neurons would not cease activity and the following should happen :
Rats were surgically prepared with electrodes for continuous electrophysiological sleep-waking recording and with implanted bilateral cannula in the LC for chemical injection. Three types of studies were conducted which are summarized as follows :
Neural Mechanism of REMS regulation has been recently modelled (Fig. 5) in Prog Neurobiol (Mallick et al., 2012); it has been mathematically reconstructed as well (Kumar et al., PLoS ONE, 2012).
Mallick and his group showed that REM sleep loss/deprivation modulated the following factors which would increase NA level in the brain. (a) The NA-ergic REM-OFF neurons, which normally cease activity during REM sleep, continue firing during REM sleep loss (Mallick et al., 1990); (b) monoamine oxidase activity decreased causing reduced breakdown of NA resulting in effective increase of NA at the synapse (Thakkar and Mallick, 1993); and (c) synthesis of tyrosine hydroxylase increased, causing increased NA synthesis in NA-ergic neurons (Majumdar and Mallick, 2003). Thus, REM sleep loss is likely to increase NA levels in the brain. iii) Mechanism of REM sleep deprivation induced increase in Na-K ATPase activity : Since NA levels increases in the brain after REM sleep deprivation, it was proposed that the elevated NA could be the candidate for mediating deprivation induced increased Na-K ATPase activity. Indeed the same was confirmed by both in vivo as well as in vitro studies (Gulyani and Mallick, 1995). Another possible action could be that the REM sleep deprivation decreased neuronal membrane fluidity which in turn might increase the Na-K ATPase activity (Mallick et al., 1995). While investigating the mechanism of action, it was found that, on one hand, the REM sleep deprivation decreased calcium levels in the synaptosome (Mallick and Gulyani, 1996), on the other hand, NA removed membrane bound calcium and increased the Na-K ATPase activity (Adya and Mallick, 1998, Mallick and Adya, 1999). At the molecular level it was found that the NA acted on α-1A adrenoceptor and intracellularly acted through IP3 mechanism to increase the Na-K ATPase activity by dephosphorylation of the enzyme (Fig. 6) (Mallick et al., 2000). Further, kinetic study showed that deprivation altered Km as well as Vmax of the enzyme suggesting that the increase in the enzyme activity was modulated allosterically as well as by increasing synthesis of the enzyme (transcriptionally) (Adya and Mallick, 2000). Allosteric modulation was shown by the above mentioned in vitro studies, while increased synthesis of the enzyme after REM sleep loss was shown subsequently (Majumdar et al., 2003). Fig. 6 
Mallick’s group’s findings suggested that the calcium ions play a complex role in regulating Na-K ATPase activity. Their systematic studies revealed that NA on one hand reduces calcium influx by closing L-type Ca-channels, while on the other hand, releases Na-K ATPase bound calcium, which dephosphorylates and stimulates Na-K ATPase activity (Fig. 7) (Das et al., 2008). Yüklə 175,31 Kb. Dostları ilə paylaş:
|
