N-methyl-d-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder

Jensen, Vidar R.; Rinholm, Johanne Egge; Johansen, Trine; Medin, Tirill; Storm‐Mathisen, Jon; Sagvolden, Terje; Hvalby, Øivind; Bergersen, Linda Hildegard

doi:10.1016/j.neuroscience.2008.05.016

Cited by 66 publications

(45 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to this finding, environmental enrichment given during development appeared to reverse the sensorimotor gating impairment produced by neonatal treatment with MK-801, DOI: 10.1159/000486391 another known NMDA antagonist [27]. In addition, Santos et al [29] reported that enrichment reduced behavioral deficits in the SHR compared to controls, and SHR have been shown to have alterations in glutamatergic receptor sensitivity [52]. Thus, it appears that environmental enrichment may be more effective with models centered around NMDA receptor manipulations, whereas enrichment does not appear to affect models that are known to manipulate the dopamine D 2 receptor, another important hallmark of schizophrenia.…”

Section: Discussionsupporting

confidence: 53%

Effects of Environmental Enrichment on Nicotine Sensitization in Rats Neonatally Treated with Quinpirole: Analyses of Glial Cell Line-Derived Neurotrophic Factor and Implications towards Schizophrenia

et al. 2018

View full text Add to dashboard Cite

The current study analyzed the effects of environmental enrichment versus isolation housing on the behavioral sensitization to nicotine in the neonatal quinpirole (NQ; dopamine D₂-like agonist) model of dopamine D₂ receptor supersensitivity, a rodent model of schizophrenia. NQ treatment in rats increases dopamine D₂ receptor sensitivity throughout the animal’s lifetime, consistent with schizophrenia. Animals were administered NQ (1 mg/kg) or saline (NS) from postnatal day (P)1 to P21, weaned, and immediately placed into enriched housing or isolated in wire cages throughout the experiment. Rats were behaviorally sensitized to nicotine (0.5 mg/kg base) or saline every consecutive day from P38 to P45, and brain tissue was harvested at P46. Results revealed that neither housing condition reduced nicotine sensitization in NQ rats, whereas enrichment reduced sensitization to nicotine in NS-treated animals. The nucleus accumbens (NAcc) was analyzed for glial cell line-derived neurotrophic factor (GDNF), a neurotrophin important in dopamine plasticity. Results were complex, and revealed that NAcc GDNF was increased in animals given nicotine, regardless of housing condition. Further, enrichment increased GDNF in NQ rats regardless of adolescent drug treatment and in NS-treated rats given nicotine, but did not increase GDNF in NS-treated controls compared to the isolated housing condition. This study demonstrates that environmental experience has a prominent impact on the behavioral and the neural plasticity NAcc response to nicotine in adolescence.

show abstract

Section: Discussionsupporting

confidence: 53%

Effects of Environmental Enrichment on Nicotine Sensitization in Rats Neonatally Treated with Quinpirole: Analyses of Glial Cell Line-Derived Neurotrophic Factor and Implications towards Schizophrenia

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In a pharmacogenomics GWAS, an SNP in glutamate receptor gene GRM7 was one of the most significant findings [138]. Glutamatergic defects have been observed in a rat model of ADHD [139,140] and magnetic resonance spectroscopy in humans shows dysregulation of glutamate and glutamate/ glutamine concentrations in ADHD patients(e.g. ref.…”

Section: The Search For Rare Genetic Variantsmentioning

confidence: 99%

Genetics of attention deficit hyperactivity disorder

2018

View full text Add to dashboard Cite

Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD's high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD's heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD's heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.Attention deficit hyperactivity disorder (ADHD) is a childhood-onset condition with impairing symptoms of inattention, impulsivity, and hyperactivity. Decades of research have documented and replicated key facts about the disorder (for a review, see ref.[1]). It occurs in about 5% of children with little geographic or cross-cultural variation in prevalence and often co-occurs with other conditions, including mood, anxiety, conduct, learning, and substance use disorders. Longitudinal studies show that two-thirds of ADHD youth will continue to have impairing symptoms of ADHD in adulthood. People with ADHD are at risk for a wide range of functional impairments: school failure, peer rejection, injuries due to accidents, criminal behavior, occupational failure, divorce, suicide, and premature death. Although many details of ADHD's pathophysiology are unknown, neuropsychological and neuroimaging studies implicate brain circuits regulating executive functioning, reward processing, timing, and temporal information processing.This article reviews data about the role that genes play in the etiology of ADHD from two perspectives. Family, twin, and adoption studies provide a firm foundation for asserting that genes are involved in the etiology of ADHD. The view from molecular genetics provides a basis for understanding mechanisms whereby genes affect biological pathways that lead to ADHD. Family, twin and adoption studies of ADHDEvidence for heritability from family, adoption, and twin studies A study of 894 ADHD probands and 1135 of their siblings aged 5-17 years old found a ninefold increased risk of ADHD in siblings of ADHD probands compared with siblings of controls [2]. Adoption studies suggest that the familial factors of ADHD are attributable to genetic factors rather than shared environmental factors [3,4] with the most recent one reporting rates of ADHD to be greater among biological relatives of non-adopted ADHD children than adoptive relatives of adopted ADHD children. The adoptive relatives had a risk for ADHD like the risk in relatives of control childr...

show abstract

“…Then sagittal sections (20-30 lm) were sliced on a freezing microtome. Free-floating sections were treated with the antibodies according to an immunofluorescent protocol (see Jensen et al, 2009). The sections were incubated in a blocking solution (2% normal calf serum) and subsequently incubated for 72 h with primary rabbit and mouse antibodies against VGLUT1 (1:18,000) and glutamine synthetase (0.3 lg/mL), respectively.…”

Section: Qualitative Confocal Microscopymentioning

confidence: 99%

VGLUT1 is localized in astrocytic processes in several brain regions

Ormel

Stensrud

Bergersen

et al. 2011

Glia

View full text Add to dashboard Cite

During the last years, the concept of gliotransmission has been established. Glutamate has been shown to be released from astrocytes by different mechanisms, e.g., in an exocytotic manner. The authors have previously shown that astrocytes in the dentate-molecular layers express vesicular glutamate transporters on synaptic-like microvesicles (SLMVs). By confocal microscopy, the authors, in this study, show that vesicles by a family of glutamate transporters 1 (VGLUT1) labeling was clearly present within astrocytic processes (diameter > 1 μm) in several brain regions; the dentate-molecular layers, the stratum radiatum of CA1 hippocampus, the frontal cortex, and the striatum. At the electron microscopic level, immunogold cytochemistry showed the presence of VGLUT1 gold particles over SLMVs in delicate astrocytic processes (cross-sectional diameter < 500 nm) in all the above-mentioned brain regions. When measuring the distance from the membrane of SLMVs in astrocytes to the closest VGLUT1 gold particle, it turned out that most gold particles (above 95 %) were located within 25 nm from the membrane, strongly suggesting that VGLUT1 is present in SLMVs in the astrocytes. Finally, electron microscopic immunocytochemistry shows that VGLUT1 labeling was concentrated in astrocytic processes from wild type, and not in VGLUT1 knock out hippocampus. The authors have concluded that astrocytes not only in the dentate-molecular layers but also in stratum radiatum of CA1 hippocampus, frontal cortex, and the striatum possess SLMVs carrying VGLUT1, suggesting that astrocytes in all these brain regions are capable of vesicular release of glutamate.

show abstract

N-methyl-d-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder

Cited by 66 publications

References 49 publications

Effects of Environmental Enrichment on Nicotine Sensitization in Rats Neonatally Treated with Quinpirole: Analyses of Glial Cell Line-Derived Neurotrophic Factor and Implications towards Schizophrenia

Effects of Environmental Enrichment on Nicotine Sensitization in Rats Neonatally Treated with Quinpirole: Analyses of Glial Cell Line-Derived Neurotrophic Factor and Implications towards Schizophrenia

Genetics of attention deficit hyperactivity disorder

VGLUT1 is localized in astrocytic processes in several brain regions

Contact Info

Product

Resources

About