Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism.

Phospholipase D3 (PLD3) polymorphisms are linked to late-onset Alzheimer's disease (LOAD). Being a lysosomal 5'-3' exonuclease, its neuronal substrates remained unknown as well as how a defective lysosomal nucleotide catabolism connects to AD-proteinopathy. We identified mitochondrial DNA (mtDNA) as a major physiological substrate and show its manifest build-up in lysosomes of PLD3-defective cells.

Sex differences in sucrose reinforcement in Long-Evans rats.

Background: There are sex differences in addiction behaviors. To develop a pre-clinical animal model to investigate this, the present study examined sex differences in sucrose taking and seeking using Long-Evans rats.

Methods: Five experiments were conducted using separate groups of subjects.

Examining persistence of acute environmental enrichment-induced anti-sucrose craving effects in rats.

A single, overnight (acute) environmental enrichment (EE; a large environment with conspecifics and novel objects) experience robustly decreases sucrose consumption (taking) and responsiveness to sucrose-paired cues (seeking) in rats. Persisting effects of acute EE on sucrose seeking and taking have not yet been identified. In the present study, rats were trained to self-administer a 10% sucrose solution paired with a compound tone + light stimulus for 10 days in 2-h sessions.

Sucrose Abstinence and Environmental Enrichment Effects on Mesocorticolimbic DARPP32 in Rats.

Dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP32) is a signaling molecule that could serve as a molecular switch, promoting or restraining sucrose seeking. We measured DARPP32 and pThr34 DARPP32 in the brains of male Long-Evans rats with a history of sucrose self-administration followed by 1 or 30 days of abstinence and exposure to either overnight (acute) or one month (chronic) environmental enrichment (EE). Brains were extracted following a 1 h cue reactivity test or no exposure to the test environment.

Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity.

Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair.

Effects of dopamine D1 and D2 receptor agonists on environmental enrichment attenuated sucrose cue reactivity in rats.

Rationale: Acute or chronic environmental enrichment (EE) reduces sucrose cue reactivity in rats. This effect may be mediated by dopamine receptors.

Objectives: We examined whether dopamine D1 or D2 receptor agonism could reverse the EE effect.