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suggest vulnerability of developing rats to arsenic.
doi:10.1016/j.ijdevneu.2012.03.266
52 P.P. Kale, V. Addepalli / Int. J. D
uickly, and they outperform both models with respect to theirlucose sensing range. Thus the most efficient model of glucoseensing of GE neurons is likely to be the DRM.
oi:10.1016/j.ijdevneu.2012.03.263
xpression of sonic hedgehog during cell proliferation in theuman cerebellum
arthiv Haldipur 1, Subashika Govindan 2,∗, Upasna Bharti 1, Chitraarkar 3, Soumya Iyengar 1, Pierre Gressens 4, Shyamala Mani 1,2
National Brain Research Centre, Manesar, IndiaIndian Institute of Science, Bangalore, IndiaAll India Institute of Medical Sciences, New Delhi, IndiaINSERM U676, Paris, France
-mail address: [email protected] (S. Govindan).Introduction: The regulation of cell proliferation in the exter-
al granular layer (EGL) of the developing cerebellum is importantor its normal patterning. An important signal that regulates EGLell proliferation is Sonic hedgehog (Shh). Shh is secreted by theurkinje cells (PC) and has a mitogenic effect on the granule cellrecursors of the EGL. Deregulation of Shh signaling has beenssociated with abnormal development and been implicated inedulloblastomas, tumors that arise from the cerebellum.Methods: We have studied the expression pattern of Shh, its
eceptors patched and smoothened, and its effectors that belong tohe Gli family of transcription factors during normal human cere-ellum development from 10 weeks of gestational age to 5 yearsost natal age and in medulloblastomas, using immunohistochem-
stry, RT-PCR and western blot analyses. This expression patterns compared to equivalent stages in the normal development oferebellum in mouse as well as in tumors.
Results: We find important differences between human andouse that reflect differences in the normal developmental pro-
ram between the two species. First, in humans there appears toe a stage of Shh signaling within the EGL when the PC are not yethe source of Shh. Secondly, unlike in the postnatal mouse cerebel-um, the expression of Shh in the PC in postnatal human cerebellums downregulated. Finally, medulloblastomas in the human but notn patched heterozygote mouse express Shh.
Discussion: Given the importance of the Shh pathway in cerebel-um development and disease there has been no prior systematictudy of its expression pattern during human cerebellum devel-pment. Our results highlight cross species differences in theegulation of the Shh signaling pathway, and a possible role in theormation of medulloblastomas.
oi:10.1016/j.ijdevneu.2012.03.264
poptosis—a probable mechanism of cell death in amyotrophicateral sclerosis? An in vitro study
. Ghosh ∗, B.K. Chandrasekhar Sagar, P.A. Alladi, T.R. Raju
National Institute of Mental Health and Neuro Sciences, India
-mail address: [email protected] (S. Ghosh).Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neu-
odegenerative disorder characterized by the loss of motor neuronsn the motor cortex, brainstem and spinal cord, resulting in deathue to respiratory failure. Prior studies from our laboratory estab-
ished that the NSC-34 motor neuron cell line is an excellent in vitroodel to unravel the basic cellular changes during its pathogenesis.arious studies have also confirmed the presence of toxic factor(s)resent in cerebrospinal fluid of ALS patients that can trigger death
uroscience 30 (2012) 640–671
of motor neurons. Accordingly, the present work was carried out tostudy the effect of cerebrospinal fluid from sporadic ALS patientson the ultrastructure of NSC-34 motor neuron cell line.
We observed the following changes:
• Alteration in the organization of mitochondrial cristae.• Margination and condensation of heterochromatin in the nucleus
(apoptotic feature).• Vacuolation and blebbing (apoptotic feature).
Apoptosis is known to progress through a series of well-definedmorphological and biochemical stages which occur in the nucleusas well as in the cytoplasm of the dying cell. The early morpho-logical events include clumping and margination of the chromatintowards the inner nuclear membrane, membrane blebbing and cel-lular shrinkage. In our study, we observed all these specific changesin the NSC-34 cells following exposure to CSF from sporadic ALSpatients. Also, our results revealed alterations in the architecture ofmitochondrial cristae which point towards probable mitochondrialdysfunction and activation of apoptotic pathways.
Thus, our study is an effort to advocate apoptosis as one of theprobable mechanisms of cell death in ALS.
doi:10.1016/j.ijdevneu.2012.03.265
Neurobehavioral modifications following arsenic exposure indeveloping rats
L.P. Chandravanshi ∗, R.S. Yadav, R.K. Shukla, A.B. Pant, V.K.Khanna
CSIR, Indian Institute of Toxicology Research, Post Box 80, MG Marg,Lucknow 226 001, India
E-mail address: [email protected] (L.P. Chandravanshi).Human exposure to arsenic, a metalloid, with extensive appli-
cations, has significantly enhanced due to anthropogenic sources.Besides, high arsenic levels in drinking water in certain regionsof the world also increase the risk of associated health problemsincluding neurological and cognitive deficits in children and adults.Keeping in view of this, the present study has been carried out toimplore the mechanism of neurobehavioral toxicity of arsenic indeveloping rats. Exposure to arsenic (2 or 4 mg/kg body weight,p.o.) in developing rats from postnatal day (PD)22–PD59 signif-icantly increased the motor activity (assessed by computerizedActimot) associated with increased binding of dopamine-D2 recep-tors (26%, 50%) and expression of tyrosine hydroxylase protein incorpus striatum PD60 as compared to controls on. Impairmentin grip strength (27%, 44%) associated with decreased binding ofmuscarinic-cholinergic receptors in hippocampus (36%, 45%) andfrontal cortex (34%, 44%) and expression of choline acetyltrans-ferase protein in hippocampus and frontal cortex was distinctlyobserved in arsenic exposed rats on PD60 as compared to con-trols. Interestingly, changes in most of these parameters remainedaltered even on withdrawal of arsenic exposure on PD90. Theresults exhibit neurobehavioral modifications involving dopami-nergic and cholinergic systems in arsenic neurotoxicity and also
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