AAV-mediated hippocampal expression of short and long Homer 1 proteins differentially affect cognition and seizure activity in adult rats

Klugmann, Matthias; Symes, C. Wymond; Leichtlein, Claudia B.; Klaussner, Bettina K.; Dunning, Jane; Fong, Dahna M.; Young, Deborah; During, Matthew J.

doi:10.1016/j.mcn.2004.10.002

Cited by 182 publications

(175 citation statements)

References 65 publications

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“…Most notably, the embryonic BDNF KO animals, when compared to the adult BDNF KO mice, reported significant expression changes in several genes related to neuronal differentiation (GAS5, NPTX2, NEUROD6, HOMER1) and GTPase activating systems (RAP1GDS1, RAN2BP2, RANGAP1). As alterations in either of these systems may lead to altered behavior, [61][62][63] we propose that some of the observed transcriptome changes, in the frontal cortex or other brain regions, are the underlying cause of the behavioral changes in the mice with conditional ablation of BDNF.…”

Section: Discussionmentioning

confidence: 99%

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

et al. 2006

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“…Since that time, 21 Homer mRNAs have been isolated from rat, mouse and human brain, however the proteins for some of these mRNAs have yet to be detected in mammalian brain tissue [107][108][109]. The mammalian genes encoding the Homer family of proteins have open reading frames that spread over 10 exons and can give rise to both constitutively expressed, as well as immediate early gene (IEG) products [102,104,110,111]. Exon 1 encodes the 5′ untranslated region (UTR) and contains the translational initiation codon ATG.…”

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

“…With the exception of the recently characterized Homer1g [111], exons 2-5 encode an Enabled/ vasodilator-stimulated phosphoprotein (Vasp) homology 1 (EVH1) domain [119,120], which is similar in sequence to other Ena/Vasp proteins that regulate cytoskeleton dynamics [121].…”

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

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Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

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“…AAVs carrying the cNDA for Homer1a, Homer1c, and Homer2b or enhanced green fluorescent protein (GFP) as a control were constructed as described previously (Klugmann et al, 2005;Szumlinski et al, 2004a). AAV infusion procedures were similar to those employed previously in mice (Szumlinski et al, 2004a(Szumlinski et al, , 2005b.…”

Section: Aav and Tat Infusionmentioning

confidence: 99%

“…After fixation, the brains were sectioned along the coronal plane on a vibratome at the level of the nucleus accumbens (100 mm; AP: + 2.2 to 1.0 mm, relative to bregma), according to the atlas of Paxinos and Watson (1986). Sections from AAV-Homer or Tat-Homer infused rats were stained with an antibody against the HA tag using standard immunocytochemical techniques as described previously for rats and mice (Klugmann et al, 2005;Szumlinski et al, 2004aSzumlinski et al, , 2005b and examined for transfection under a light microscope. Sections from AAV-GFP infused rats were examined for cellular transfection using a fluorescent microscope.…”

Section: Verification Of Transfectionmentioning

confidence: 99%

Homer Isoforms Differentially Regulate Cocaine-Induced Neuroplasticity

Szumlinski

Abernathy

Oleson

et al. 2005

Neuropsychopharmacol

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Homer proteins modulate neuroplasticity in excitatory synapses and are dynamically regulated by cocaine. Whereas acute cocaine elevates immediate-early gene (short) isoforms of Homer1 in the nucleus accumbens, withdrawal from repeated cocaine administration downregulates the expression of constitutive Homer1 isoforms. The present study determined whether or not this downregulation in constitutive Homer expression in the accumbens is necessary for enduring alterations in cocaine-induced changes in the brain and behavior. The long vs short Homer isoforms were overexpressed in the rat nucleus accumbens during drug abstinence, and the adaptations elicited by repeated cocaine on glutamate transmission and motor behavior were measured. It was found that both chronic and acute overexpression of constitutive, but not short, Homer isoforms abolished cocaine-induced sensitization of locomotor hyperactivity and prevented the development of glutamate abnormalities in the accumbens, including the reduction in basal extracellular glutamate content and the sensitized glutamate response to a subsequent cocaine challenge injection. Together, these data indicate that the enduring reduction of long Homer isoforms in the nucleus accumbens of cocaine-withdrawn rats is necessary for the expression of cocaine-induced neuroplasticity.

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AAV-mediated hippocampal expression of short and long Homer 1 proteins differentially affect cognition and seizure activity in adult rats

Cited by 182 publications

References 65 publications

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

Homers regulate drug-induced neuroplasticity: Implications for addiction

Homer Isoforms Differentially Regulate Cocaine-Induced Neuroplasticity

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