Paulose,C S; Peeyush, K T; Anju, T R(Springer Science+Business Media, LLC 2009, 2009)
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Abstract:
Hypoxia in neonates can lead to biochemical
and molecular alterations mediated through changes in
neurotransmitters resulting in permanent damage to brain.
In this study, we evaluated the changes in the receptor
status of GABAA in the cerebral cortex and brainstem of
hypoxic neonatal rats and hypoxic rats supplemented with
glucose and oxygen using binding assays and gene
expression of GABAAa1 and GABAAc5. In the cerebral
cortex and brainstem of hypoxic neonatal rats, a significant
decrease in GABAA receptors was observed, which
accounts for the respiratory inhibition. Hypoxic rats sup-
plemented with glucose alone and with glucose and oxygen
showed, respectively, a reversal of the GABAA receptors,
andGABAAa1 and GABAAc5 gene expression to control.
Glucose acts as an immediate energy source thereby
reducing the ATP-depletion-induced increase in GABA
and oxygenation, which helps in encountering anoxia.
Resuscitation with oxygen alone was less effective in
reversing the receptor alterations. Thus, the results of this
study suggest that reduction in the GABAA receptors
functional regulation during hypoxia plays an important
role in mediating the brain damage. Glucose alone and
glucose and oxygen supplementation to hypoxic neonatal
rats helps in protecting the brain from severe hypoxic
damage.
Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous
seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated
with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory
action on cerebellar function through 5HT2C receptors. 5-HT2C receptors are novel targets for developing anticonvulsant
drugs. In the present study, we investigated the changes in the 5-HT2C receptors binding and gene
expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a
significant down regulation of the 5-HT content (pb0.001), 5-HT2C gene expression (pb0.001) and 5-HT2C
receptor binding (pb0.001) with an increased affinity (pb0.001). Carbamazepine and B. monnieri treatments
to epileptic rats reversed the down regulated 5-HT content (pb0.01), 5-HT2C receptor binding (pb0.001) and
gene expression (pb0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and
recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the
upregulation of 5-HT2C receptor in epileptic rats. This has clinical significance in the management of epilepsy
Paulose,C S; Athira, Babu; Anju, T R(Indian Journal of Biochemistry and Biophysics, April , 2009)
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Abstract:
Hypoxia is one of the major causes of damage to the fetal and neonatal brain and cardiac functions. in earlier studies we have reported the brain damage caused by hypoxia and resusciation with oxygen and epinephrine and have found that glucose treatment to hypoxic rats and hypoxic rats treated with oxygen shows a reversal of brain damage. during this study the findings may have clinical significance in the proper management of heart and brain functions.
Paulose,C S; Akash,George K; Anju, T R; Peeyush, K T(Journal of Biomedical Science(2008) 15:623–631, June 7, 2008)
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Abstract:
Dopamine D2 receptors are involved in ethanol
self- administration behavior and also suggested to mediate
the onset and offset of ethanol drinking. In the present
study, we investigated dopamine (DA) content and Dopamine
D2 (DA D2) receptors in the hypothalamus and corpus
striatum of ethanol treated rats and aldehyde dehydrogenase
(ALDH) activity in the liver and plasma of ethanol
treated rats and in vitro hepatocyte cultures. Hypothalamic
and corpus striatal DA content decreased significantly
(P\0.05, P\0.001 respectively) and homovanillic acid/
dopamine (HVA/DA) ratio increased significantly
(P\0.001) in ethanol treated rats when compared to
control. Scatchard analysis of [3H] YM-09151-2 binding to
DA D2 receptors in hypothalamus showed a significant
increase (P\0.001) in Bmax without any change in Kd in
ethanol treated rats compared to control. The Kd of DA D2
receptors significantly decreased (P\0.05) in the corpus
striatum of ethanol treated rats when compared to control.
DA D2 receptor affinity in the hypothalamus and corpus
striatum of control and ethanol treated rats fitted to a single
site model with unity as Hill slope value. The in vitro
studies on hepatocyte cultures showed that 10-5 M and
10-7 M DA can reverse the increased ALDH activity in
10% ethanol treated cells to near control level. Sulpiride,
an antagonist of DA D2, reversed the effect of dopamine on
10% ethanol induced ALDH activity in hepatocytes. Our
results showed a decreased dopamine concentration with
enhanced DA D2 receptors in the hypothalamus and corpus
striatum of ethanol treated rats. Also, increased ALDH was observed in the plasma and liver of ethanol treated rats and
in vitro hepatocyte cultures with 10% ethanol as a compensatory
mechanism for increased aldehyde production
due to increased dopamine metabolism. A decrease in
dopamine concentration in major brain regions is coupled
with an increase in ALDH activity in liver and plasma,
which contributes to the tendency for alcoholism. Since the
administration of 10-5 M and 10-7 M DA can reverse the
increased ALDH activity in ethanol treated cells to near
control level, this has therapeutic application to correct
ethanol addicts from addiction due to allergic reaction
observed in aldehyde accumulation.
Paulose,C S; Kanungo, M S(Department of Biotecnology, April 21, 1982)
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Abstract:
The binding of (-)[ 3H ]dihydroalprenolol , an antagonist of norepinephrine , to $-adrenergic receptors
in different regions of the brain of male and female rats of various ages was measured . The binding to the
synaptosomal fraction of corpus striatum , hypothalamus, cerebral cortex, cerebellum and the brainstems
shows a significant decrease in the binding in old rats of both sexes . Only in the female corpus striatal
region, the binding in the adult and the old is the same . In the case of females, the highest binding is seen
in the young. In the male, an increase in binding occurs up to adulthood , after which it declines,
suggesting a definite sex-related difference in the Q-adrenergic receptor.