Hypoglycemia induced behavioural deficit and decreased GABA receptor, CREB expression in the cerebellum of streptozoticin induced diabetic rats

Sherin, Akhtar; Peeyush, Kumar T.; George, Naijil; Chinthu, R.; Paulose, C S

doi:10.1016/j.brainresbull.2010.09.004

Cited by 16 publications

(10 citation statements)

References 54 publications

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“…The same picture is found in the cerebellum, where GABA receptors are involved in control of coordination and motor learning and, like in the cerebral cortex, play a critical role in neuronal excitability and modulation of synaptic neurotransmission (Luján, 2007). In the cerebellum of STZ rats with hyperglycemia the gene expression of GABA Aα1 subunit and glutamate decarboxylase was decreased and these molecular alterations were exacerbated by recurrent hypoglycemia (Sherin et al, 2010). The gene expression of CREB, a stimulus-inducible transcription activator implicated in the activation of protein synthesis required for long-term memory and seizure formation, was significantly down regulated in DM and recurrent hypoglycemia.…”

Section: Gaba Signalingmentioning

confidence: 70%

“…The gene expression of CREB, a stimulus-inducible transcription activator implicated in the activation of protein synthesis required for long-term memory and seizure formation, was significantly down regulated in DM and recurrent hypoglycemia. Since CREB up-regulates endogenous GABA Aα1 transcription, the decreased expression of CREB in the cerebellum of hypoglycemic and hyperglycemic rats led to the attenuation of GABAergic system and, as a result, to excitotoxic damage of neuronal cells (Sherin et al, 2010). It follows that hypo-and hyperglycemia in DM both decrease GABAergic neuroprotective function in the cerebral cortex and cerebellum, which accounts for increased vulnerability of these brain areas to subsequent neuronal damage.…”

Section: Gaba Signalingmentioning

confidence: 99%

See 1 more Smart Citation

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Шпаков¹,

Chistyakova²,

Derkach³

et al. 2011

Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring

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Section: Gaba Signalingmentioning

confidence: 70%

Section: Gaba Signalingmentioning

confidence: 99%

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Шпаков¹,

Chistyakova²,

Derkach³

et al. 2011

Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring

View full text Add to dashboard Cite

“…Recently, it was shown that insulin-induced hypoglycemic and streptozotocin-induced diabetic rats exhibit significantly decreased expression of GABRA1 with reduced cortical GABA binding (Antony et al 2010; Sherin et al 2010, 2012), indicating that Network 2 shown in Figure 3 B also represents the effects of insulin signaling impairment owing to the decreased expression of PCSK1 and PCSK2. Moreover, silencing of the CPLX1 gene, which is also part of Network 2 and which was also downregulated in AD brains (Fig.…”

Section: Discussionmentioning

confidence: 99%

Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

et al. 2013

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Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM.

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“…The studies related to cognition and behavior following diabetes is limited to the hippocampal atrophy and allied cellular changes. A sole study reported the role of cerebellar alterations in behavioral deficits following hypoglycaemia in terms of decreased GABA receptor and CREB expression (Sherin et al, 2010). Cerebellum is associated with emotion, cognition and behavior (Rapoport et al, 2000; Schmahmann and Caplan, 2006) and alterations to the cerebellum lead to motor deficits, dementia, schizophrenia and other psychiatric disorders (Baldaçara et al, 2008; Sui and Zhang, 2012).…”

Section: Discussionmentioning

confidence: 99%

Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

Nagayach

Patro

2014

Front. Cell. Neurosci.

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Behavioral impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45 mg/kg body weight; intraperitoneally). Motor function alterations were studied using Rotarod test (motor coordination) and grip strength (muscle activity) at 2nd, 4th, 6th, 8th, 10th, and 12th week post-diabetic confirmation. Scenario of glial (astroglia and microglia) activation, cell death and glutamate transportation was gaged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labeling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioral alterations following STZ-induced diabetes.

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Hypoglycemia induced behavioural deficit and decreased GABA receptor, CREB expression in the cerebellum of streptozoticin induced diabetic rats

Cited by 16 publications

References 54 publications

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

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