Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

Chepkova, A. N.; Schönfeld, Susanne; Sergeeva, Olga A.

doi:10.1155/2015/458123

Cited by 8 publications

(6 citation statements)

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“…Aging-related increases in astrocyte activation, determined by GFAP mRNA and protein expression, have been found in several areas of the brain including CORT [83,84], CERE [83], striatum [85], and hippocampus [86]. We showed in this study that long-term Tat expression led to increased GFAP expression in both CORT and CPU, decreased GFAP expression in CERE and no changes in HIP (Fig.…”

Section: Discussionsupporting

confidence: 60%

Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

Zhao

Fan²,

Vann³

et al. 2020

Aging and disease

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HIV infects the central nervous system and causes HIV/neuroAIDS, which is predominantly manifested in the form of mild cognitive and motor disorder in the era of combination antiretroviral therapy. HIV Tat protein is known to be a major pathogenic factor for HIV/neuroAIDS through a myriad of direct and indirect mechanisms. However, most, if not all of studies involve short-time exposure of recombinant Tat protein in vitro or short-term Tat expression in vivo. In this study, we took advantage of the doxycycline-inducible brainspecific HIV-1 Tat transgenic mouse model, fed the animals for 12 months, and assessed behavioral, pathological, and epigenetic changes in these mice. Long-term Tat expression led to poorer short-and long-term memory, lower locomotor activity and impaired coordination and balance ability, increased astrocyte activation and compromised neuronal integrity, and decreased global genomic DNA methylation. There were sex-and brain region-dependent differences in behaviors, pathologies, and epigenetic changes resulting from long-term Tat expression. All these changes are reminiscent of accelerated aging, raising the possibility that HIV Tat contributes, at least in part, to HIV infection-associated accelerated aging in HIV-infected individuals. These findings also suggest another utility of this model for HIV infection-associated accelerated aging studies.

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Section: Discussionsupporting

confidence: 60%

Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

Zhao

Fan²,

Vann³

et al. 2020

Aging and disease

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“…We performed a between-genotypes comparison of mRNA levels encoding for the selected neurotransmitter receptors, enzymes and structural proteins involved in synaptic plasticity. Using first PCR array “Mouse Nitric Oxide Signaling Pathway” (PAMM-062Z, SA Bioscience) as described in Chepkova et al 25. we detected a 2-fold upregulation of beta-actin expression in striatal tissue of LGS-ko mice with no change in any other gene transcripts when reactions were normalized on beta-2-microglobulin (B2m), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glucuronidase beta (Gusb).…”

Section: Resultsmentioning

confidence: 98%

“…We analyzed the expression of genes encoding receptors for neurotransmitters, known to be involved in hippocampal and corticostriatal plasticity (glutamate, dopamine, acetylcholine, endocannabinoids) and other plasticity-related proteins. Detailed description of the applied protocol was presented previously25. The relative mRNA level encoding each gene was estimated by the 2 −ΔΔCt method described previously2578, where ΔCt = Ct target gene – Ct Rpl13a (ribosomal protein L13a).…”

Section: Methodsmentioning

confidence: 99%

“…Detailed description of the applied protocol was presented previously25. The relative mRNA level encoding each gene was estimated by the 2 −ΔΔCt method described previously2578, where ΔCt = Ct target gene – Ct Rpl13a (ribosomal protein L13a). Rpl13a was selected as the most appropriate housekeeping gene using criteria described previously7980.…”

Section: Methodsmentioning

confidence: 99%

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Impaired novelty acquisition and synaptic plasticity in congenital hyperammonemia caused by hepatic glutamine synthetase deficiency

Chepkova

Sergeeva

Görg

et al. 2017

Sci Rep

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Genetic defects in ammonia metabolism can produce irreversible damage of the developing CNS causing an impairment of cognitive and motor functions. We investigated alterations in behavior, synaptic plasticity and gene expression in the hippocampus and dorsal striatum of transgenic mice with systemic hyperammonemia resulting from conditional knockout of hepatic glutamine synthetase (LGS-ko). These mice showed reduced exploratory activity and delayed habituation to a novel environment. Field potential recordings from LGS-ko brain slices revealed significantly reduced magnitude of electrically-induced long-term potentiation (LTP) in both CA3-CA1 hippocampal and corticostriatal synaptic transmission. Corticostriatal but not hippocampal slices from LGS-ko brains demonstrated also significant alterations in long-lasting effects evoked by pharmacological activation of glutamate receptors. Real-time RT-PCR revealed distinct patterns of dysregulated gene expression in the hippocampus and striatum of LGS-ko mice: LGS-ko hippocampus showed significantly modified expression of mRNAs for mGluR1, GluN2B subunit of NMDAR, and A1 adenosine receptors while altered expression of mRNAs for D1 dopamine receptors, the M1 cholinoreceptor and the acetylcholine-synthetizing enzyme choline-acetyltransferase was observed in LGS-ko striatum. Thus, inborn systemic hyperammonemia resulted in significant deficits in novelty acquisition and disturbed synaptic plasticity in corticostriatal and hippocampal pathways involved in learning and goal-directed behavior.

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“…Several studies have shown age-related modifications in the NMDA receptor-NO-cGMP cascade in the CNS (Peterson and Cotman, 1989 ; Tamaru et al, 1991 ; Wenk et al, 1991 ; Vallebuona and Raiteri, 1995 ; Wardas et al, 1997 ; Ossowska et al, 2001 ; Chepkova et al, 2015 ). In addition, the aging process is associated with a progressive decline in NKA activity, both centrally and peripherally (Scavone et al, 2000 ; Kawamoto et al, 2008 ; Vasconcelos et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

The Influence of Na+, K+-ATPase on Glutamate Signaling in Neurodegenerative Diseases and Senescence

et al. 2016

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Decreased Na+, K+-ATPase (NKA) activity causes energy deficiency, which is commonly observed in neurodegenerative diseases. The NKA is constituted of three subunits: α, β, and γ, with four distinct isoforms of the catalytic α subunit (α1−4). Genetic mutations in the ATP1A2 gene and ATP1A3 gene, encoding the α2 and α3 subunit isoforms, respectively can cause distinct neurological disorders, concurrent to impaired NKA activity. Within the central nervous system (CNS), the α2 isoform is expressed mostly in glial cells and the α3 isoform is neuron-specific. Mutations in ATP1A2 gene can result in familial hemiplegic migraine (FHM2), while mutations in the ATP1A3 gene can cause Rapid-onset dystonia-Parkinsonism (RDP) and alternating hemiplegia of childhood (AHC), as well as the cerebellar ataxia, areflexia, pescavus, optic atrophy and sensorineural hearing loss (CAPOS) syndrome. Data indicates that the central glutamatergic system is affected by mutations in the α2 isoform, however further investigations are required to establish a connection to mutations in the α3 isoform, especially given the diagnostic confusion and overlap with glutamate transporter disease. The age-related decline in brain α2∕3 activity may arise from changes in the cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase (PKG) pathway. Glutamate, through nitric oxide synthase (NOS), cGMP and PKG, stimulates brain α2∕3 activity, with the glutamatergic N-methyl-D-aspartate (NMDA) receptor cascade able to drive an adaptive, neuroprotective response to inflammatory and challenging stimuli, including amyloid-β. Here we review the NKA, both as an ion pump as well as a receptor that interacts with NMDA, including the role of NKA subunits mutations. Failure of the NKA-associated adaptive response mechanisms may render neurons more susceptible to degeneration over the course of aging.

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Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

Cited by 8 publications

References 74 publications

Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

Impaired novelty acquisition and synaptic plasticity in congenital hyperammonemia caused by hepatic glutamine synthetase deficiency

The Influence of Na+, K+-ATPase on Glutamate Signaling in Neurodegenerative Diseases and Senescence

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