VCP/p97 Mediates Dynein-Dependent Retrograde Mitochondrial Motility in Axons.

Valosin-containing protein (VCP), also called p97, is an evolutionarily conserved and ubiquitously expressed ATPase with diverse cellular functions. Dominant mutations in are found in a late-onset multisystem degenerative proteinopathy. The neurological manifestations of the disorder include frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).

Importance of D1 and D2 receptor stimulation for the induction and expression of cocaine-induced behavioral sensitization in preweanling rats.

The behavioral manifestations of psychostimulant-induced sensitization vary markedly between young and adult rats, suggesting that the neural mechanisms mediating this phenomenon differ across ontogeny. In this project we examined the importance of D1 and D2 receptors for the induction and expression of cocaine-induced behavioral sensitization during the preweanling period. In the behavioral experiments, rats were injected with reversible D1 and/or D2 antagonists (SCH23390 and/or raclopride) or an irreversible receptor antagonist (EEDQ) either before cocaine administration on the pretreatment day (induction) or before cocaine challenge on the test day (expression).

Functional Impairment in Miro Degradation and Mitophagy Is a Shared Feature in Familial and Sporadic Parkinson's Disease.

Mitochondrial movements are tightly controlled to maintain energy homeostasis and prevent oxidative stress. Miro is an outer mitochondrial membrane protein that anchors mitochondria to microtubule motors and is removed to stop mitochondrial motility as an early step in the clearance of dysfunctional mitochondria. Here, using human induced pluripotent stem cell (iPSC)-derived neurons and other complementary models, we build on a previous connection of Parkinson's disease (PD)-linked PINK1 and Parkin to Miro by showing that a third PD-related protein, LRRK2, promotes Miro removal by forming a complex with Miro.

Effects of D2 or combined D1/D2 receptor antagonism on the methamphetamine-induced one-trial and multi-trial behavioral sensitization of preweanling rats.

Rationale: There is suggestive evidence that the neural mechanisms mediating one-trial and multi-trial behavioral sensitization differ, especially when the effects of various classes of dopamine (DA) agonists are examined.

Objective: The purpose of the present study was to determine the role of the D2 receptor for the induction of one-trial and multi-trial methamphetamine sensitization in preweanling rats.

Methods: In a series of experiments, rats were injected with saline or raclopride (a selective D2 receptor antagonist), either alone or in combination with SCH23390 (a selective D1 receptor antagonist), 15 min prior to treatment with the indirect DA agonist methamphetamine.

Role of the D1 receptor for the dopamine agonist-induced one-trial behavioral sensitization of preweanling rats.

Rationale: The neural mechanisms mediating the ontogeny of behavioral sensitization are poorly understood.

Objective: The purpose of the present study was to determine the role of the D1 receptor for the induction of dopamine agonist-induced behavioral sensitization during the preweanling period.

Methods: In the first experiment, the early ontogeny of R-propylnorapomorphine (NPA)-induced behavioral sensitization was examined by pretreating male and female rats with saline or NPA (0.

Behavioral effects of dopamine receptor inactivation during the adolescent period: age-dependent changes in dorsal striatal D2(High) receptors.

Rationale: Dopamine (DA) receptor inactivation produces opposing behavioral effects across ontogeny. For example, inactivating DA receptors in the dorsal striatum attenuates DA agonist-induced behaviors of adult rats, while potentiating the locomotor activity of preweanling rats.

Objective: The purpose of this study was to determine if DA receptor inactivation potentiates the DA agonist-induced locomotor activity of adolescent rats and whether alterations in D2(High) receptors are responsible for this effect.

Behavioral effects of dopamine receptor inactivation in the caudate-putamen of preweanling rats: role of the D2 receptor.

Rationale: Inactivating dopamine (DA) receptors in the caudate-putamen (CPu) attenuates basal and DA agonist-induced behaviors of adult rats while paradoxically increasing the locomotor activity of preweanling rats.

Objective: The purpose of this study was to determine (a) whether D1 or D2 receptor inactivation is responsible for the elevated locomotion shown by preweanling rats and (b) whether DA receptor inactivation produces a general state in which any locomotor-activating drug will cause a potentiated behavioral response.

Methods: Dimethyl sulfoxide (DMSO) or N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was bilaterally infused into the CPu on postnatal day (PD) 17.