• Shashi Wadhwa

      Articles written in Journal of Biosciences

    • Immunohistochemical analysis of glutamate, cholecystokinin and vasoactive intestinal polypeptide in the lateral geniculate complex of albino rat: A developmental study

      Shashi Wadhwa Geeta Jotwani

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      The lateral geniculate nuclear complex of albino rats was investigated with respect to the development of neurotransmitters/neuromodulators such as glutamate, cholecystokinin and vasoactive intestinal polypeptide at gestational day 18, various postnatal age periods and in the adult using immunohistochemical methods. The study shows the unequivocal presence of and the sequential changes in the profile of glutamate while cholecystokinin and vasoactive intestinal polypeptide are not demonstrable at any of the age periods. Glutamate is seen both in the cells and fibres from 40 postnatal day onwards and immunoreactivity is more intense in the adult. The findings are discussed with relevance to the role of neurotransmitters in development.

    • Nitric oxide synthase immunoreactivity in the developing and adult human retina

      Shashi Wadhwa Tapas C Nag

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      Nitric oxide synthase (NOS) catalyzes the formation of nitric oxide (NO) from L-arginine. In this study, the cellular localization of neuronal NOS (nNOS) activity in the human retina since fetal development was examined by immunohistochemistry. No detectable staining in the fetal retina was present at 14 weeks of gestation (wg), the earliest age group examined. A centro-peripheral gradient of development of nNOS immunoreactivity was evident at 16–17 wg, with the midperipheral retina showing nNOS immunoreactivity in most of the cell types and the inner plexiform layer while the peripheral part demonstrated moderate immunoreactivity only in the ganglion cell layer and photoreceptor precursors. A transient increase in nNOS immunoreactivity in the ganglion cells and Müller cell endfeet between 18–19 and 24–25 wg was observed at the time when programmed cell death in the ganglion cell layer, loss of optic nerve fibres as well as increase in glutamate immunoreactivity and parvalbumin (a calcium binding protein) immunoreactivity in the ganglion cells was reported. These observations indicate that programmed cell death of ganglion cells in the retina may be linked to glutamate toxicity and NO activity, as also suggested by others in the retina and cerebral cortex.

      The presence of nNOS immunoreactivity in the photoreceptors from 16–17 weeks of fetal life to adulthood indicates other functions, besides their involvement in photoreceptor function of transduction and information processing.

    • Differential expression of syntaxin-1 and synaptophysin in the developing and adult human retina

      T C Nag Shashi Wadhwa

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      Synaptophysin and syntaxin-1 are membrane proteins that associate with synaptic vesicles and presynaptic active zones at nerve endings, respectively. The former is known to be a good marker of synaptogenesis; this aspect, however, is not clear with syntaxin-1. In this study, the expression of both proteins was examined in the developing human retina and compared with their distribution in postnatal to adult retinas, by immunohistochemistry. In the inner plexiform layer, both were expressed simultaneously at 11–12 weeks of gestation, when synaptogenesis reportedly begins in the central retina. In the outer plexiform layer, however, the immunoreactivities were prominent by 16 weeks of gestation. Their expression in both plexiform layers followed a centre-to-periphery gradient. The immunoreactivities for both proteins were found in the immature photoreceptor, amacrine and ganglion cells; however, synaptophysin was differentially localized in bipolar cells and their axons, and syntaxin was present in some horizontal cells. In postnatal-to-adult retinas, synaptophysin immunoreactivity was prominent in photoreceptor terminals lying in the outer plexiform layer; on the contrary, syntaxin-1 was present in a thin immunoreactive band in this layer. In the inner plexiform layer, however, both were homogeneously distributed. Our study suggests that (i) syntaxin-1 appears in parallel with synapse formation; (ii) synaptogenesis in the human retina might follow a centre-to-periphery gradient; (iii) syntaxin-1 is likely to be absent from ribbon synapses of the outer plexiform layer, but may occur at presynaptic terminals of photoreceptor and horizontal cells, as is apparent from its localization in these cells, which is hitherto unreported for any vertebrate retina.

    • The enigma of morphine tolerance: Recent insights

      Subrata Basu Ray Shashi Wadhwa

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    • Expression of the neurotrophin receptors Trk A and Trk B in adult human astrocytoma and glioblastoma

      Shashi Wadhwa Tapas C Nag Anupam Jindal Rahul Kushwaha Ashok K Mahapatra Chitra Sarkar

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      Neurotrophins and their receptors of the Trk family play a critical role in proliferation, differentiation and survival of the developing neurons. There are reports on their expression in neoplasms too, namely, the primitive neuroectodermal tumours of childhood, and in adult astrocytic gliomas. The involvement of Trk receptors in tumour pathogenesis, if any, is not known. With this end in view, the present study has examined 10 tumour biopsy samples (identified as astrocytoma, pilocytic astrocytoma and glioblastoma) and peritumoral brain tissue of adult patients, for the presence of Trk A and Trk B receptors, by immunohistochemistry. The nature of the tumour samples was also confirmed by their immunoreactivity (IR) to glial fibrillary acidic protein. In the peritumoral brain tissue, only neurons showed IR for Trk A and Trk B. On the contrary, in the tumour sections, the IR to both receptors was localized in the vast majority of glia and capillary endothelium. There was an obvious pattern of IR in these gliomas: high levels of IR were present in the low-grade (type I and II) astrocytoma; whereas in the advanced malignant forms (WHO grade IV giant cell glioblastoma and glio-blastoma multiforme) the IR was very weak. These findings suggest that Trk A and Trk B are involved in tumour pathogenesis, especially in the early stage, and may respond to signals that elicit glial proliferation, and thus contribute to progression towards malignancy.

    • Enhanced analgesic effect of morphine-nimodipine combination after intraspinal administration as compared to systemic administration in mice

      Dilip Verma Subrata Basu Ray Ishan Patro Shashi Wadhwa

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      Calcium plays an important role in the pathophysiology of pain. A number of studies have investigated the effect of L-type calcium channel blockers on the analgesic response of morphine. However, the results are conflicting. In the present study, the antinociceptive effect of morphine (2–5 Μg) and nimodipine (1 Μg) co-administered intraspinally in mice was observed using the tail flick test. It was compared to the analgesic effect of these drugs (morphine — 250 Μg subcutaneously; nimodipine — 100 Μg intraperitoneally) after systemic administration. Nimodipine is highly lipophilic and readily crosses the blood brain barrier. Addition of nimodipine to morphine potentiated the analgesic response of the latter when administered through the intraspinal route but not when administered through systemic route. It may be due to direct inhibitory effect of morphine and nimodipine on neurons of superficial laminae of the spinal cord after binding to Μ-opioid receptors and L-type calcium channels respectively.

    • Role of sound stimulation in reprogramming brain connectivity

      Sraboni Chaudhury Tapas C Nag Suman Jain Shashi Wadhwa

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      Sensory stimulation has a critical role to play in the development of an individual. Environmental factors tend to modify the inputs received by the sensory pathway. The developing brain is most vulnerable to these alterations and interacts with the environment to modify its neural circuitry. In addition to other sensory stimuli, auditory stimulation can also act as external stimuli to provide enrichment during the perinatal period. There is evidence that suggests that enriched environment in the form of auditory stimulation can play a substantial role in modulating plasticity during the prenatal period. This review focuses on the emerging role of prenatal auditory stimulation in the development of higher brain functions such as learning and memory in birds and mammals. The molecular mechanisms of various changes in the hippocampus following sound stimulation to effect neurogenesis, learning and memory are described. Sound stimulation can also modify neural connectivity in the early postnatal life to enhance higher cognitive function or even repair the secondary damages in various neurological and psychiatric disorders. Thus, it becomes imperative to examine in detail the possible ameliorating effects of prenatal sound stimulation in existing animal models of various psychiatric disorders, such as autism.

    • Expressions of visual pigments and synaptic proteins in neonatal chick retina exposed to light of variable photoperiods

      KUMAR ABHIRAM JHA TAPAS C NAG SHASHI WADHWA TARA SANKAR ROY

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      Light causes damage to the retina, which is one of the supposed factors for age-related macular degeneration inhuman. Some animal species show drastic retinal changes when exposed to intense light (e.g. albino rats). Althoughbirds have a pigmented retina, few reports indicated its susceptibility to light damage. To know how light influences acone-dominated retina (as is the case with human), we examined the effects of moderate light intensity on the retina ofwhite Leghorn chicks (Gallus g. domesticus). The newly hatched chicks were initially acclimatized at 500 lux for 7days in 12 h light: 12 h dark cycles (12L:12D). From posthatch day (PH) 8 until PH 30, they were exposed to 2000 luxat 12L:12D, 18L:6D (prolonged light) and 24L:0D (constant light) conditions. The retinas were processed fortransmission electron microscopy and the level of expressions of rhodopsin, S- and L/M cone opsins, and synapticproteins (Synaptophysin and PSD-95) were determined by immunohistochemistry and Western blotting. Rearing in24L:0D condition caused disorganization of photoreceptor outer segments. Consequently, there were significantlydecreased expressions of opsins and synaptic proteins, compared to those seen in 12L:12D and 18L:6D conditions.Also, there were ultrastructural changes in outer and inner plexiform layer (OPL, IPL) of the retinas exposed to24L:0D condition. Our data indicate that the cone-dominated chick retina is affected in constant light condition, withchanges (decreased) in opsin levels. Also, photoreceptor alterations lead to an overall decrease in synaptic proteinexpressions in OPL and IPL and death of degenerated axonal processes in IPL.

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