Platelet prostaglandin E1 hyposensitivity in schizophrenia: Reduction of prostaglandin E1- or forskolin-stimulated cyclic AMP response in platelets

Ofuji, M; Kaiya, Hisanobu; Nozaki, Masakatsu; Tsurumi, Kaito

doi:10.1016/0024-3205(89)90079-9

Cited by 8 publications

(1 citation statement)

References 18 publications

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“…Cyclic nucleotide signaling specifically within the ventral hippocampal formation (VHIPP) may be particularly important because VHIPP lesions and knockdown of CREB in the rodent VHIPP impair social behaviors (Kogan et al, 2000; Brightwell et al, 2005; Tseng et al, 2009). This is consistent with the fact that both cyclic nucleotide signaling deficits (Ebstein et al, 1976; Belmaker et al, 1978; Bowers and Study, 1979; Kafka et al, 1979, 1986; Hoshino et al, 1980; Garver et al, 1982; Gattaz et al, 1983; Kafka and van Kammen, 1983; Memo et al, 1983; Goldberg et al, 1984; Kanof et al, 1986, 1987, 1989; Lerer et al, 1987; Ofuji et al, 1989; Kaiya et al, 1990; Kang, 1990; Young et al, 1991, 1993, 1994; Kaiya, 1992; Cowburn et al, 1994; Avissar et al, 1997; Gurguis et al, 1997, 1999a,b; Rahman et al, 1997; Avissar et al, 2001a,b; Bacchelli et al, 2003; Edmunds et al, 2008; Kelley et al, 2008; Turetsky and Moberg, 2009; Woolfrey et al, 2009; Ji et al, 2011) and abnormalities in the VHIPP (Suddath et al, 1990; Shenton et al, 1992; Rajarethinam et al, 2001; Jessen et al, 2003; Pegues et al, 2003; Lee et al, 2004; Rametti et al, 2007; Rusch et al, 2008; Zhou et al, 2008; Ghose et al, 2009; Nesvaderani et al, 2009; Schobel et al, 2009a,b; Hall et al, 2010; Goldman et al, 2011; Zhang et al, 2011) (referred to as the anterior hippocampus in primates) are observed in patients with neuropsychiatric disorders in which social deficits are known to occur.…”

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confidence: 87%

PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain

et al. 2016

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Despite the fact that appropriate social behaviors are vital to thriving in one’s environment, little is understood of the molecular mechanisms controlling social behaviors or how social experience sculpts these signaling pathways. Here, we determine if Phosphodiesterase 11A (PDE11A), an enzyme that is restricted to the ventral hippocampal formation (VHIPP) and that breaks down cAMP and cGMP, regulates social behaviors. PDE11 wild-type (WT), heterozygous (HT), and knockout (KO) mice were tested in various social approach assays and gene expression differences were measured by RNA sequencing. The effect of social isolation on PDE11A4 compartmentalization and subsequent social interactions and social memory was also assessed. Deletion of PDE11A triggered age- and sex-dependent deficits in social approach in specific social contexts but not others. Mice appear to detect altered social behaviors of PDE11A KO mice, because C57BL/6J mice prefer to spend time with a sex-matched PDE11A WT vs. its KO littermate; whereas, a PDE11A KO prefers to spend time with a novel PDE11A KO vs. its WT littermate. Not only is PDE11A required for intact social interactions, we found that 1 month of social isolation vs. group housing decreased PDE11A4 protein expression specifically within the membrane fraction of VHIPP. This isolation-induced decrease in PDE11A4 expression appears functional because social isolation impairs subsequent social approach behavior and social memory in a PDE11A genotype-dependent manner. Pathway analyses following RNA sequencing suggests PDE11A is a key regulator of the oxytocin pathway and membrane signaling, consistent with its pivotal role in regulating social behavior.

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Section: Introductionsupporting

confidence: 87%

PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain

et al. 2016

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Platelets in Neurological Disorders

Canobbio

Guidetti

Torti

2017

Platelets in Thrombotic and Non-Thrombotic Disorders

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A Role for Phosphodiesterase 11A (PDE11A) in the Formation of Social Memories and the Stabilization of Mood

Kelly

2017

Advances in Neurobiology

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The most recently discovered 3′,5′-cyclic nucleotide phosphodiesterase family is the Phosphodiesterase 11 (PDE11) family, which is encoded by a single gene PDE11A. PDE11A is a dual-specific PDE, breaking down both cAMP and cGMP. There are four PDE11A splice variants (PDE11A1–4) with distinct tissue expression profiles and unique N-terminal regulatory regions, suggesting that each isoform could be individually targeted with a small molecule or biologic. PDE11A4 is the PDE11A isoform expressed in brain and is found in the hippocampal formation of humans and rodents. Studies in rodents show that PDE11A4 mRNA expression in brain is, in fact, restricted to the hippocampal formation (CA1, possibly CA2, subiculum, and the adjacently connected amygdalohippocampal area). Within the hippocampal formation of rodents, PDE11A4 protein is expressed in neurons but not astrocytes, with a distribution across nuclear, cytoplasmic, and membrane compartments. This subcellular localization of PDE11A4 is altered in response to social experience in mouse, and in vitro studies show the compartmentalization of PDE11A4 is controlled, at least in part, by homodimerization and N-terminal phosphorylation. PDE11A4 expression dramatically increases in the hippocampus with age in the rodent hippocampus, from early postnatal life to late aging, suggesting PDE11A4 function may evolve across the lifespan. Interestingly, PDE11A4 protein shows a 3–10-fold enrichment in the rodent ventral hippocampal formation (VHIPP; a.k.a. anterior in primates) versus dorsal hippocampal formation (DHIPP). Consistent with this enrichment in VHIPP, studies in knockout mice show that PDE11A regulates the formation of social memories and the stabilization of mood and is a critical mechanism by which social experience feeds back to modify the brain and subsequent social behaviors. PDE11A4 likely controls behavior by regulating hippocampal glutamatergic, oxytocin, and cytokine signaling, as well as protein translation. Given its unique tissue distribution and relatively selective effects on behavior, PDE11A may represent a novel therapeutic target for neuropsychiatric, neurodevelopmental, or age-related disorders. Therapeutically targeting PDE11A4 may be a way to selectively restore aberrant cyclic nucleotide signaling in the hippocampal formation while leaving the rest of the brain and periphery untouched, thus, relieving deficits while avoiding unwanted side effects.

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Platelet prostaglandin E1 hyposensitivity in schizophrenia: Reduction of prostaglandin E1- or forskolin-stimulated cyclic AMP response in platelets

Cited by 8 publications

References 18 publications

PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain

PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain

Platelets in Neurological Disorders

A Role for Phosphodiesterase 11A (PDE11A) in the Formation of Social Memories and the Stabilization of Mood

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